BLOOD DISEASES
A circulating fluid all over our body.
BLOOD CELL DISORDERS
DEFINITION
A blood cell disorder is a condition in which there’s a problem with your red blood cells, white blood cells, or the smaller, circulating cells called platelets, which are critical for clot formation. All three cell types form in the bone marrow, which is the soft tissue inside your bones. Red blood cells transport oxygen to your body’s organs and tissues. White blood cells help your body fight infections. Platelets help your blood to clot. Blood cell disorders impair the formation and function of one or more of these types of blood cells.
What Are the Types of Blood Cell Disorders?
There are many types of blood cell disorders that can drastically affect your overall health.
Sickle cell anaemia (SCA) is a type of anaemia that draws its name from the unusual sickled shape of the affected red blood cells. A normal red blood cell is shaped like a disc, but due to a genetic mutation, the red blood cells of people with sickle cell anaemia contain abnormal haemoglobin molecules and so are rigid and curved. The sickle-shaped red blood cells can’t carry as much oxygen to your tissues as normal red blood cells can. They may also become stuck in your blood vessels, blocking blood flow to your organs.
SCA is an inherited disease that passes down to children if both parents have the condition. It’s most common among African-Americans.
Having too few platelets is quite dangerous because even a small injury can cause serious blood loss. If you have too many platelets in your blood, blood clots can form and block a major artery, causing a stroke or heart attack. Sometimes, deformed platelets can’t stick to other blood cells or the walls of your blood vessels and so can’t clot properly. This can also lead to a dangerous loss of blood.
SIGN AND SYMPTOMS
There are several symptoms of blood cells disorders and the symptoms will vary depending on the type of blood cell disorder.
Common symptoms of red blood cell disorders are:
CAUSES
Blood cell disorders may be the result of disease. They may also be hereditary, or inherited from parents. For example, an iron deficiency due a lack of iron in the diet or problems with absorbing iron can result in your body not being able to produce enough red blood cells. A genetic condition, such as polycythemia vera, can cause it to produce too many.
If you have an autoimmune disease, such as lupus, your immune system may destroy your own blood platelets. This will hamper your body’s ability to stop episodes of bleeding.
Low or compromised white blood cells are due to infections that destroy or overwhelm them. Some health conditions destroy white blood cells faster than the bone marrow can produce them. Your body may also increase its production of white blood cells to fight a disease or infection.
You or your child may be at risk for red blood cell disorders if you have low blood iron levels. You may be at risk for white blood cell disorders if you have a serious infection or autoimmune disease. A family history of blood cell disorders puts you at a higher risk of having one.
DIAGNOSIS
Your doctor may order several tests, including a complete blood count (CBC) to see how many of each type of blood cell you have. Your doctor may also order a bone marrow biopsy to see if there are any abnormal cells developing in your marrow. This will involve removing a small amount of bone marrow for testing.
TREATMENT
The treatment plan depends on the stage of illness, age, and overall health status. Doctors may use a combination of treatments to help correct blood cell disorders.
· Medication
For platelet disorders, medications such as Nplate (romiplostim) can treat clotting problems. For white blood cell disorders, antibiotics can help fight infections. Dietary supplements such as iron and vitamin B-9 or B-12 can treat anemia due to deficiencies. Vitamin B-9 is also called folate, and vitamin B-12 is also known as cobalamin.
· Surgery
Bone marrow transplants may repair or replace damaged marrow. These involve transferring stem cells, usually from a donor, to your body to help your bone marrow begin producing normal blood cells. A blood transfusion is another option to help you replace lost or damaged blood cells. During a blood transfusion, you receive an infusion of healthy blood from a donor.
Both procedures require specific criteria to succeed. Bone marrow donors must match or be as close as possible to the genetic profile while blood transfusions require a donor with a compatible blood type.
What is the long-term outlook?
The variety of blood cell disorders means that your experience of living with one of these conditions may vary greatly from someone else. Early diagnosis and treatment are the best ways to ensure that you live a healthy and full life with a blood cell disorder.
Different side effects of treatments vary depending on the person. Research your options, and speak with your doctor to find the right treatment for you.Finding a support group or counsellor to help you deal with any emotional stress about having a blood cell disorder is also helpful.
A-Z List of Blood Disorders
Doctors see people with a wide range of blood disorders, including cancers, anaemias, hemoglobinopathies, bone marrow failure syndromes, bleeding disorders, platelet disorders, blood clots (thrombosis), plasma cell disorders, and other blood-related problems (including rare disorders, like POEMS syndrome).
These are the list for blood diseases. Click on the disorder name for more information.
A-C
T-Z
A blood cell disorder is a condition in which there’s a problem with your red blood cells, white blood cells, or the smaller, circulating cells called platelets, which are critical for clot formation. All three cell types form in the bone marrow, which is the soft tissue inside your bones. Red blood cells transport oxygen to your body’s organs and tissues. White blood cells help your body fight infections. Platelets help your blood to clot. Blood cell disorders impair the formation and function of one or more of these types of blood cells.
What Are the Types of Blood Cell Disorders?
There are many types of blood cell disorders that can drastically affect your overall health.
- Red Blood Cell Disorders
Sickle cell anaemia (SCA) is a type of anaemia that draws its name from the unusual sickled shape of the affected red blood cells. A normal red blood cell is shaped like a disc, but due to a genetic mutation, the red blood cells of people with sickle cell anaemia contain abnormal haemoglobin molecules and so are rigid and curved. The sickle-shaped red blood cells can’t carry as much oxygen to your tissues as normal red blood cells can. They may also become stuck in your blood vessels, blocking blood flow to your organs.
SCA is an inherited disease that passes down to children if both parents have the condition. It’s most common among African-Americans.
- Platelet Disorders
Having too few platelets is quite dangerous because even a small injury can cause serious blood loss. If you have too many platelets in your blood, blood clots can form and block a major artery, causing a stroke or heart attack. Sometimes, deformed platelets can’t stick to other blood cells or the walls of your blood vessels and so can’t clot properly. This can also lead to a dangerous loss of blood.
- Paediatric White Blood Cell Disorders
SIGN AND SYMPTOMS
There are several symptoms of blood cells disorders and the symptoms will vary depending on the type of blood cell disorder.
Common symptoms of red blood cell disorders are:
- fatigue
- shortness of breath
- trouble concentrating from lack of oxygenated blood in the brain
- muscle weakness
- a fast heartbeat
- chronic infections
- fatigue
- unexplained weight loss
- malaise, or a general feeling of being unwell
- cuts or sores that don’t heal or are slow to heal
- blood that doesn’t clot after an injury or cut
- skin that bruises easily
- unexplained nosebleeds or bleeding from the gums
CAUSES
Blood cell disorders may be the result of disease. They may also be hereditary, or inherited from parents. For example, an iron deficiency due a lack of iron in the diet or problems with absorbing iron can result in your body not being able to produce enough red blood cells. A genetic condition, such as polycythemia vera, can cause it to produce too many.
If you have an autoimmune disease, such as lupus, your immune system may destroy your own blood platelets. This will hamper your body’s ability to stop episodes of bleeding.
Low or compromised white blood cells are due to infections that destroy or overwhelm them. Some health conditions destroy white blood cells faster than the bone marrow can produce them. Your body may also increase its production of white blood cells to fight a disease or infection.
- Risk Factors:
You or your child may be at risk for red blood cell disorders if you have low blood iron levels. You may be at risk for white blood cell disorders if you have a serious infection or autoimmune disease. A family history of blood cell disorders puts you at a higher risk of having one.
DIAGNOSIS
Your doctor may order several tests, including a complete blood count (CBC) to see how many of each type of blood cell you have. Your doctor may also order a bone marrow biopsy to see if there are any abnormal cells developing in your marrow. This will involve removing a small amount of bone marrow for testing.
TREATMENT
The treatment plan depends on the stage of illness, age, and overall health status. Doctors may use a combination of treatments to help correct blood cell disorders.
· Medication
For platelet disorders, medications such as Nplate (romiplostim) can treat clotting problems. For white blood cell disorders, antibiotics can help fight infections. Dietary supplements such as iron and vitamin B-9 or B-12 can treat anemia due to deficiencies. Vitamin B-9 is also called folate, and vitamin B-12 is also known as cobalamin.
· Surgery
Bone marrow transplants may repair or replace damaged marrow. These involve transferring stem cells, usually from a donor, to your body to help your bone marrow begin producing normal blood cells. A blood transfusion is another option to help you replace lost or damaged blood cells. During a blood transfusion, you receive an infusion of healthy blood from a donor.
Both procedures require specific criteria to succeed. Bone marrow donors must match or be as close as possible to the genetic profile while blood transfusions require a donor with a compatible blood type.
What is the long-term outlook?
The variety of blood cell disorders means that your experience of living with one of these conditions may vary greatly from someone else. Early diagnosis and treatment are the best ways to ensure that you live a healthy and full life with a blood cell disorder.
Different side effects of treatments vary depending on the person. Research your options, and speak with your doctor to find the right treatment for you.Finding a support group or counsellor to help you deal with any emotional stress about having a blood cell disorder is also helpful.
A-Z List of Blood Disorders
Doctors see people with a wide range of blood disorders, including cancers, anaemias, hemoglobinopathies, bone marrow failure syndromes, bleeding disorders, platelet disorders, blood clots (thrombosis), plasma cell disorders, and other blood-related problems (including rare disorders, like POEMS syndrome).
These are the list for blood diseases. Click on the disorder name for more information.
A-C
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML) (and the subtype acute promyelocytic leukemia, APL)
- Amyloidosis
- Anemia
- Aplastic anemia
- Bone marrow failure syndromes, inherited
- Chronic lymphocytic leukemia (CLL)
- Chronic myeloid leukemia (CML)
- Deep vein thrombosis (DVT)
- Diamond-Blackfan anemia
- Dyskeratosis congenita (DKC)
- Eosinophilic disorders
- Essential thrombocythemia
- Fanconi anemia
- Gaucher disease
- Hemochromatosis
- Hemolytic anemia
- Hemophilia
- Hereditary spherocytosis
- Hodgkin’s lymphoma
- Idiopathic thrombocytopenic purpura (ITP)
- Inherited bone marrow failure syndromes
- Iron-deficiency anemia
- Langerhans cell histiocytosis
- Leukemia
- Leukopenia
- Mastocytosis
- Multiple myeloma
- Myelodysplastic syndromes (MDS)
- Myelofibrosis
- Myeloproliferative neoplasms (MPN)
- Non-Hodgkin’s lymphoma
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Pernicious anemia (B12 deficiency)
- Polycythemia vera
- Porphyria
- Pulmonary embolism (PE)
- Shwachman-Diamond syndrome (SDS)
- Sickle cell disease
T-Z
- Thalassemias
- Thrombocytopenia
- Thrombotic thrombocytopenic purpura (TTP)
- Venous thromboembolism
- Von Willebrand disease
- Waldenstrom’s macroglobulinemia (lymphoplasmacytic lymphoma)
LEUKEMIA
![Picture](/uploads/8/0/7/8/80782094/8430545.png?316)
DEFINITION
Leukemia is cancer of the white blood cells. White blood cells help our bodies to fight infection. Blood cells are formed in bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. These cells crowd out the healthy blood cells, making it hard for blood to do its work.Leukemia can develop very quickly or slowly. For instance, chronic leukemia grows slowly. However, in acute leukemia, the cells are very abnormal and their number increases rapidly. Adults can get either type; while children with leukemia most often have an acute type. Some leukemias can often be cured. Other types are hard to cure, but you can often control them. Treatments may include chemotherapy, radiation and stem cell transplantation. Even if symptoms disappear, you might need therapy to prevent a relapse.
TYPES OF LEUKEMIA
Chronic and Acute
Experts divide leukemia into four large groups, each of which can be Acute, which is a rapidly progressing disease that results in the accumulation of immature, useless cells in the marrow and blood, or Chronic, which progresses more slowly and allows more mature, useful cells to be made. In other words, acute leukemia crowds out the good cells more quickly than chronic leukemia.
Lymphocytic and Myelogenous
Leukemias are also subdivided into the type of affected blood cell. If the cancerous transformation occurs in the type of marrow that makes lymphocytes, the disease is called lymphocytic leukemia. A lymphocyte is a kind of white blood cell inside the vertebrae immune system. If the cancerous change occurs in the type of marrow cells that go on to produce red blood cells, other types of white cells, and platelets, the disease is called myelogenous leukemia.
The following are the four main types of leukemia disease:
- Acute Lymphocytic Leukemia (ALL), also known as Acute Lymphoblastic Leukemia - This is the most common type of leukemia among young children, although adults can get it as well, especially those over the age of 65. Survival rates of at least five years range from 85% among children and 50% among adults. The following are all subtypes of this leukemia: precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia.
- Chronic Lymphocytic Leukemia (CLL) - This is most common among adults over 55, although younger adults can get it as well. CLL hardly ever affects children. The majority of patients with CLL are men, over 60%. 75% of treated CLL patients survive for over five years. Experts say CLL is incurable. A more aggressive form of CLL is B-cell prolymphocytic leukemia.
- Acute Myelogenous Leukemia (AML) - AML is more common among adults than children, and affects males significantly more often than females. Patients are treated with chemotherapy. 40% of treated patients survive for over 5 years. The following are subtypes of AMS - acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.
- Chronic Myelogenous Leukemia (CML) - The vast majority of patients are adults. 90% of treated patients survive for over 5 years. Gleevec (imatinib) is commonly used to treat CML, as well as some other drugs. Chronic monocytic leukemia is a subtype of CML.
SIGN AND SYMPTOMS
- Blood clotting is poor - As immature white blood cells crowd out blood platelets, which are crucial for blood clotting, the patient may bruise or bleed easily and heal slowly - he may also develop petechiae (a small red to purple spot on the body, caused by a minor hemorrhage).
- Affected immune system - The patient's white blood cells, which are crucial for fighting off infection, may be suppressed or not working properly. The patient may experience frequent infections, or his immune system may attack other good body cells.
- Anaemia - As the shortage of good red blood cells grows the patient may suffer from anaemia - this may lead to difficult or labored respiration (dyspnea) and pallor (skin has a pale color caused by illness).
- Other symptoms - Patients may also experience nausea, fever, chills, night sweats, flu-like symptoms, and tiredness. If the liver or spleen becomes enlarged the patient may feel full and will eat less, resulting in weight loss. Headache is more common among patients whose cancerous cells have invaded the CNS (central nervous system).
- Precaution - As all these symptoms could be due to other illnesses. A diagnosis of leukemia can only be confirmed after medical tests are carried out.
CAUSES
Experts say that different leukemias have different causes. The following are either known causes, or strongly suspected causes:
- Artificial ionizing radiation
- Viruses - HTLV-1 (human T-lymphotropic virus) and HIV (human immunodeficiency virus)
- Benzene and some petrochemicals
- Alkylating chemotherapy agents used in previous cancers
- Maternal fetal transmission (rare)
- Hair dyes
- Genetic predisposition - some studies researching family history and looking at twins have indicated that some people have a higher risk of developing leukemia because of a single gene or multiple genes.
- Down syndrome - people with Down syndrome have a significantly higher risk of developing leukemia, compared to people who do not have Down syndrome. Experts say that because of this, people with certain chromosomal abnormalities may have a higher risk.
- Electromagnetic energy - studies indicate there is not enough evidence to show that ELF magnetic (not electric) fields that exist currently might cause leukemia. The IARC (International Agency for Research on Cancer) says that studies which indicate there is a risk tend to be biased and unreliable.
DIAGNOSIS
Doctors may find chronic leukemia in a routine blood test, before symptoms begin. If this happens, or if you have signs or symptoms that suggest leukemia, you may undergo the following diagnostic exams:
- Physical exam. Your doctor will look for physical signs of leukemia, such as pale skin from anemia, swelling of your lymph nodes, and enlargement of your liver and spleen.
- Blood tests. By looking at a sample of your blood, your doctor can determine if you have abnormal levels of white blood cells or platelets — which may suggest leukemia.
- Bone marrow test. Your doctor may recommend a procedure to remove a sample of bone marrow from your hipbone. The bone marrow is removed using a long, thin needle. The sample is sent to a laboratory to look for leukemia cells. Specialized tests of your leukemia cells may reveal certain characteristics that are used to determine your treatment options.
TREATMENT
- As the various types of leukemias affect patients differently, their treatments depend on what type of leukemia they have. The type of treatment will also depend on the patient's age and state of health.
- In order to get the most effective treatment the patient should get treatment at a center where doctors have experience and are well trained in treating leukemia patients. As treatment has improved, the aim of virtually all health care professionals should be complete remission - that the cancer goes away completely for a minimum of five years after treatment.
- Treatment for patients with acute leukemias should start as soon as possible - this usually involves induction therapy with chemotherapy, and takes place in a hospital.
- When a patient is in remission he will still need consolidation therapy or post induction therapy. This may involve chemotherapy, as well as a bone marrow transplant (allogeneic stem cell transplantation).
- If a patient has Chronic Myelogenous Leukemia (CML) his treatment should start as soon as the diagnosis is confirmed. He will be given a drug, probably Gleevec (imatinib mesylate), which blocks the BCR-ABL cancer gene. Gleevec stops the CML from getting worse, but does not cure it. There are other drugs, such as Sprycel (dasatinib) and Tarigna (nilotinb), which also block the BCR-ABL cancer gene. Patients who have not had success with Gleevec are usually given Sprycel and Tarigna. All three drugs are taken orally. A bone marrow transplant is the only current way of curing a patient with CML. The younger the patient is the more likely the transplant will be successful.
- Synribo (omacetaxine mepesuccinate) was approved by the FDA, on 26th October 2012, for the treatment of chronic myelogenous leukemia (CML) in adult patients who had been treated with at least two drugs, but whose cancer continued to progress. Resistance to medications is common in CML. Synribo is an alkaloid from Cephalotaxus harringtonia which inhibits proteins that trigger the development of cancerous cells. The drug is administered subcutaneously.
- Patients with Chronic Lymphocytic Leukemia (CLL) may not receive any treatment for a long time after diagnosis. Those who do will normally be given chemotherapy or monoclonal antibody therapy. Some patients with CLL may benefit from allogeneic stem cell transplantation (bone marrow transplant).
- Rabbit antibodies help Leukemia patients - scientists from Virginia Commonwealth University reported in the journal Bone Marrow Transplantation (July 2012 issue) that rabbit antibodies can improve survival and reduce the occurrence of relapses in patients with leukemia and myelodysplasia who are receiving a stem transplant from an unrelated donor.
- Leukemia patients' own T-cells achieve remission for over two years - patients who were infused with their own T-cells after they had been genetically altered to fight cancer tumors stayed in full remission for over 24 months. Researchers from the Perelman School of Medicine at the University of Pennsylvania presented their findings at the American Society of Hematology's Annual Meeting and Exposition in December 2012. All those who took part in the human study had advanced cancers - ten of them had chronic lymphocytic leukemia, and two children had acute lymphoblastic leukemia.
- All leukemia patients, regardless of what type they have or had, will need to be checked regularly by their doctors after the cancer has gone (in remission). They will undergo exams and blood tests. The doctors will occasionally test their bone marrow. As time passes and the patient continues to remain free of leukemia the doctor may decide to lengthen the intervals between tests.
- New leukemia immune cell therapy shows promise - New findings on cell therapy to treat leukemia bring more encouraging news of the promise that this experimental area of cancer treatment holds for patients for whom conventional approaches do not work. The research was published in the journal Science Translational Medicine in February 2014.
FAST FACTS ABOUT LEUKEMIA
- There are about 54,270 new cases of leukemia in the US each year.
- Around 24,450 people die from leukemia per year in the US.
- There are about 20,830 new cases of acute myeloid leukemia (AML) and 10,460 deaths from AML in the US each year, most cases are adults.
- Leukemia is the seventh leading cause of cancer death in the United States.
- Approximately 1.5% of men and women will be diagnosed with leukemia at some point during their lifetime.
- Compared to other cancers, leukemia is relatively rare.
- Although leukemia is among the most common childhood cancers, it most often occurs in older adults.
- Leukemia is slightly more common in men than women.
- People with leukemia have many treatment options, and treatment for leukemia can often control the disease and its symptoms.
MYELOMA
![Picture](/uploads/8/0/7/8/80782094/510003_orig.jpg)
DEFINITION
Myeloma, also known as multiple myeloma, is a cancer arising from plasma cells, a type of white blood cell which is made in the bone marrow. Bone marrow is the ‘spongy’ material found in the centre of the larger bones in the body. The bone marrow is where all blood cells are made. Plasma cells form part of your immune system. Normal plasma cells produce antibodies, also called immunoglobulins, to help fight infection. In myeloma, these plasma cells become abnormal, multiply uncontrollably and release only one type of antibody – known as paraprotein – which has no useful function. It is often through the measurement of this paraprotein that myeloma is diagnosed and monitored. Unlike many cancers, myeloma does not exist as a lump or tumour. Most of the medical problems related to myeloma are caused by the build-up of the abnormal plasma cells in the bone marrow and the presence of the paraprotein in the blood or in the urine.
Myeloma affects multiple places in the body (hence ‘multiple’ myeloma) where bone marrow is normally active in an adult i.e. within the bones of the spine, skull, pelvis, the rib cage, long bones of the arms and legs and the areas around the shoulders and hips.
Myeloma is a relapsing-remitting cancer. This means there are periods when the myeloma is causing symptoms and/or complications and needs to be treated, followed by periods of remission or plateau where the myeloma does not cause symptoms and does not require treatment.
SIGN AND SYMPTOMS
Unlike many other cancers, myeloma can affect the body in several ways. Most of the medical problems related to myeloma are caused by the build-up of the abnormal plasma cells in the bone marrow and the presence of the paraprotein in the blood or in the urine.
The most common symptoms and complications include:
- Pain: the principal cause of pain for myeloma patients is myeloma bone disease. Effective control and management of pain is an important aspect of myeloma treatment
- Bone disease: the middle or lower back, the rib cage and the hips are the most frequently affected places
- Fatigue: due to the myeloma itself, to one or more of its complications (e.g. anaemia), or it can be a side-effect of treatment
- Recurring infection: common in myeloma patients because the myeloma and its treatments interfere with the immune system
- Anaemia: a reduction in the number of red blood cells. It can occur as a result of the myeloma or as a side-effect of treatment and can cause fatigue, weakness or breathlessness
- Kidney damage: can be caused by the myeloma itself or as a side-effect of treatment
- Hypercalcaemia: a condition in which the level of calcium in the blood is too high. It can occur as a result of myeloma bone disease and can cause thirst, nausea, vomiting, confusion and/or constipation
- Peripheral neuropathy: damage to the nerves that make up the peripheral nervous system. It can be caused by the treatments for myeloma and also the myeloma itself
CAUSES AND RISK FACTORS
The cause of multiple myeloma has not yet been identified. Although scientists have made advancements in understanding how multiple myeloma develops, it is unclear as to what exactly causes the disease.
Multiple Myeloma Risk factors
Research suggests possible associations with a decline in the immune system, certain occupations, exposure to certain chemicals, and exposure to radiation. However, there are no strong connections, and, in most cases, multiple myeloma develops in individuals who have no known risk factors. Multiple myeloma may also be the result of several risk factors acting together.
While multiple myeloma is not considered to be a hereditary disease, research has found that genetic factors may influence the development of multiple myeloma.
How Multiple Myeloma Develops
Normal plasma cells develop into malignant plasma cells through a multistep process. When plasma cells become malignant, they grow out of control, dividing rapidly. Soon, there are too many malignant cells, and they begin to crowd out normal cells in the bone marrow. Malignant plasma cells may invade the hard outer part of the bone and then spread into the cavities of the large bones in the body and form a tumor. When only one tumor is formed, it is called a solitary plasmacytoma. When multiple small tumors are formed, the disease is multiple myeloma.
DIAGNOSIS
The diagnosis of multiple myeloma is determined by a number of different diagnostic tests, because myeloma is difficult to diagnose on the basis of any single laboratory test result. Accurate diagnosis generally results from consideration of several factors, including physical evaluation, patient history, symptoms, and diagnostic testing results. The initial evaluation to help confirm a diagnosis of myeloma includes blood and urine tests as well as a bone marrow biopsy. Other tests include X-rays. MRIs, CT scans and PET scans.
The standards for diagnosing multiple myeloma are determined by the myeloma diagnostic criteria. This currently requires confirmation of one major and one minor criteria or three minor criteria in a patient displaying symptoms of myeloma. The diagnostic criteria helps to determine the classification of multiple myeloma, whether it is smouldering myeloma (asymptomatic), symptomatic myeloma, or MGUS.
Having all of the appropriate multiple myeloma tests done is very important, as the results will help your doctor better determine treatment options and a prognosis. Many of these tests are also used to assess the extent of the disease and to plan and monitor treatment.
Genomics testing
Researchers are continually working to better understand the biology of multiple myeloma, and through genomic (study of the tumor cell DNA) studies we have learned that there are many DNA alterations in myeloma cells. The ultimate goal of genomic research is to eventually develop personalized treatments based on the DNA in the myeloma cells of individual patients.
Genomic tests are conducted by analyzing the DNA from the myeloma cells taken from a small amount of bone marrow. Tests are conducted as part of the initial diagnosis and may be repeated periodically. The most common tests are karyotyping and FISH. Other more sensitive tests are used in research studies, and some cancer centers are beginning to use them as well.
To date, there is no evidence to suggest that multiple myeloma is inherited, and the changes in the DNA are most likely due to mutations in the cells that occur in patients over time.
While certain DNA alterations are indicative of how aggressive the myeloma is, patients with DNA alterations do not necessarily have a worse prognosis.
So far, there is limited information from genomic studies to guide treatment decisions, with a few notable exceptions, for example, DNA alteration t(4;14), a chromosomal abnormality . Studies have shown that patients with t(4;14) have better outcomes when treated with a proteasome inhibitor, such as Velcade®.
Since researchers have not yet found any reason to believe that multiple myeloma is inherited, genetic testing is not recommended for family members.
TREATMENT
Multiple myeloma treatment options have increased significantly over the last 10 years. New multiple myeloma treatments have resulted in improved survival rates among myeloma patients. Even more encouraging, there are many promising new therapies under investigation now. We are not just accelerating the development of the next multiple myeloma treatment, but by seeking to customize treatments based on our mapping of a patient’s genome, we are accelerating the development of the right treatment for each patient who urgently needs it.
Treatment for myeloma is aimed at disease control, relieving the complications and symptoms it causes, and extending and improving the quality of patients’ lives.
Myeloma treatment is almost always with a combination of drugs over periods of time known as cycles. Cycles may last from weeks to months.
Treatment combinations are usually made up of two or three different types of drugs which work well together and can include chemotherapy drugs (e.g. cyclophosphamide and melphalan), steroids (e.g. dexamethasone and prednisolone) and other types of anti-myeloma drugs (e.g. thalidomide, Velcade® and Revlimid®).
The importance of genomics
One area researchers are working on is better understanding the biology of multiple myeloma. Through genomic studies (studies of the tumor cell DNA), we have learned that there are many DNA alterations in myeloma cells, and these frequently differ from patient to patient. The ultimate goal of genomic research is to develop personalized treatments based on the DNA in the myeloma cells of individual patients. These frequently differ from patient to patient. There is not one set of defining alterations.
Today, we know that certain DNA alterations indicate how aggressive the myeloma is and, in some cases, test results can help guide treatment decisions or determine eligibility for multiple myeloma clinical trials.
DNA alterations and treatment
For most DNA alterations, there are not enough data to guide treatment decisions. An exception is t(4;14). This is one of a type of chromosomal abnormalities called translocation in which a chromosome breaks and a portion of it reattaches to a different chromosome.
Studies have shown that patients with t(4;14) have better outcomes when treated with a proteasome inhibitor, such as Velcade.
Factors determining multiple myeloma treatment
There is no one standard multiple myeloma treatment. A patient’s individual treatment plan is based on a number of things, including:
- Age and general health
- Results of laboratory and cytogenetic (genomic) tests
- Symptoms and disease complications
- Prior myeloma treatment
- Patient’s lifestyle, goals, views on quality of life, and personal preferences
EXTRA INFORMATION
- Myeloma, also known as multiple myeloma, is a cancer arising from plasma cells, a type of cell made in the bone marrow that forms part of your immune system
- Unlike many other cancers, myeloma does not exist as a lump or tumour
- The most common symptoms of myeloma include bone pain, recurring infection, kidney damage and fatigue. Not everyone will experience all or any of these
- There are approximately 4,800 people diagnosed with myeloma every year in the UK. It is the second most common form of bone marrow cancer, but only represents 1% of all cancers
- The causes of myeloma are not fully understood but it is thought to be caused by an interaction of both genetic and environmental factors
- Myeloma is a very individual cancer, both in terms of what symptoms and complications patients can have and in the way they respond to treatment
- Myeloma is a relapsing-remitting cancer. This means there are periods when the myeloma is causing symptoms and needs to be treated, followed by periods of stable disease where the myeloma does not cause symptoms and does not require treatment
- Treatment for myeloma is most effective when two or more drugs with different but complementary mechanisms of action are given in combination
- Other treatment will also be prescribed to help prevent or manage potential side-effects of treatment combinations and treat the symptoms and complications of myeloma
- Improvements made to treatment over the last decade has meant that survival rates in myeloma are increasing at the fastest rate among all cancer types in the UK
HEMOCHROMATOSIS
![Picture](/uploads/8/0/7/8/80782094/8562611.png?721)
DEFINITION
Hemochromatosis is an iron disorder in which the body simply loads too much iron. This action is genetic and the excess iron, if left untreated, can damage joints, organs, and eventually be fatal.
There are several types of hemochromatosis. Type 1, also called Classic Hemochromatosis (HHC), is a leading cause of iron overload disease. People with HHC (too much iron) absorb extra amounts of iron from the daily diet. The human body cannot rid itself of extra iron. Over time, these excesses build up in major organs such as the heart, liver, pancreas, joints, and pituitary. If the extra iron is not removed, these organs can become diseased. Untreated hemochromatosis can be fatal.
Iron is an essential nutrient found in many foods. Iron carries oxygen (in haemoglobin) to all parts of the body. Normally, humans absorb about 8-10% of the iron in foods that they eat. People with hemochromatosis (too much iron) can absorb four times more iron than normal.
Undiagnosed and untreated hemochromatosis (too much iron) increases the risk for diseases and conditions such as:
- Diabetes mellitus
- Irregular heart beat or heart attack
- Arthritis (osteoarthritis, osteoporosis)
- Cirrhosis of the liver or liver cancer
- Gall bladder disease
- Depression
- Impotence
- Infertility
- Hypothyroidism
- Hypogonadism
- Some cancers
SIGNS AND SYMPTOMS
Chronic fatigue and joint pain are the most common complaints of people with hemochromatosis. For this reason, the complete diagnosis is often delayed because these two symptoms are commonly seen in other diseases. Pain in the knuckles of the pointer and middle finger, collectively called “The Iron Fist,” is the only sign or symptom specific to hemochromatosis. However, not everyone with HHC experiences the Iron Fist.
Patients often complain of the following:
Some complain of the following symptoms, although these indicators are not always specific to hemochromatosis:
- Lack of energy
- Abdominal pain
- Memory fog
- Loss of sex drive
- Heart flutters
- Irregular heart beat
DISEASES THAT CAN DEVELOP IF LEFT UNTREATED
- Bone and joint: osteoarthritis or osteoporosis in knuckles, ankles, and hips
- Liver: enlarged liver, cirrhosis, cancer, and liver failure diabetes
- Skin: abnormal color (bronze, reddish or ashen-gray)
- Heart: irregular heartbeat, enlarged heart, congestive heart failure
- Endocrine: diabetes, hypothyroidism, hypogonadism, (infertility, impotence), hormone imbalances
- Spleen: enlarged spleen
CAUSES AND RISK FACTORS
Type I hemochromatosis is caused by defects (mutations) in the HFE gene. HFE has many purposes, but one important role is that it helps to control the amount of iron that is absorbed from food. There are several known mutations in the HFE gene, but presently testing for only three is available: C282Y, H63D, and S65C.
Everyone inherits two copies of HFE, one from Mom and one from Dad.
When a person has one mutated copy, he or she is called a carrier or heterozygote. When a person has two of the same mutated copies, he or she is called a homozygote. When a person has two different – but mutated – copies, he or she is called a compound heterozygote.
Genetics can be very difficult to understand at first. What is most important is that you know which gene combination causes the greatest known risk of loading iron.
Risk can be modified by other genes, the environment, or unknown factors. Therefore, anyone with a mutated copy of HFE should periodically ask their doctor to check iron levels through haemoglobin, fasting serum iron, TIBC, and serum ferritin.
DIAGNOSIS
There are 3 tests that together make up the Iron Panel Test. These tests look at serum ferritin, Total iron binding capacity, and serum iron. These tests need to be taken as a panel, not independently, to receive a comprehensive and accurate assessment of a potential Hemochromatosis diagnosis.
SERUM IRON (SI)
This test is best conducted after fasting for at least three hours. Also, iron or vitamin C supplements should be discontinued at least three days before taking the test. Do not discontinue other medication unless your doctor tells you to.
SERUM FERRITIN (SF)
This test measures the amount of iron contained or stored in the body. Serum ferritin reference ranges are different for adults and children. For adults, the ideal range is 50-150 ng/ml.
TOTAL IRON BINDING CAPACITY (TIBC)
This test tells how well your body can bind to iron. Serum iron divided by TIBC x 100% gives you important information about the transferrin-iron saturation percentage (TS%). TS% is usually 25-35%; in some people with iron overload, the TS% is very high. There are other types of iron overload where the TS% is normal.
In the past, liver biopsy was widely used to diagnose hemochromatosis. Today, liver biopsy is not necessary to diagnose the inherited form of HHC. DNA tests are available to determine if a person has genetic hemochromatosis.
Physicians who can help diagnose hemochromatosis
If there are complications with diseased organs, the patient might need to see a specialist:
- Cardiologist
- Endocrinologist
- Gastroenterologist
- Gynecologist
- Hematologist/Oncologist
- Hepatologist
- Internist
- Rheumatologist
- Urologist
- Psychiatrist
TREATMENT
It is very important to get iron levels down to normal. Therapeutic blood removal, or phlebotomy, is the most common means of iron reduction. Therapeutic phlebotomy (TP) is the same as regular blood donation but TP requires a doctor’s order (prescription).
Regular blood donation can be done every 8 weeks. A person with severe iron overload may need to give blood as much as 8 times in a single month! The goal is to bring blood ferritin levels to an ideal range of 50-150ng/mL. Depending on the amount of iron overload at the time of diagnosis, reaching normal levels can require several phlebotomies.
Serum ferritin drops about 30ng/mL with each full unit (500cc) of blood removed. When ferritin falls more rapidly following a phlebotomy, there is likely some other reason for the fast rate other than the blood donation. These reasons are specific to the individual but can include the presence of inflammation, changes in alcohol consumption, or changes to medication.
Once iron levels reach normal, a person can begin maintenance therapy, which involves making a blood donation every 2 to 4 months for life. Some people may need to give blood more or less depending on what they eat and how quickly their body absorbs iron.
The TS% and serum ferritin tests can be done periodically to help determine how often blood should be removed.
When hemochromatosis is diagnosed early and treated before organs are damaged, a person can live a normal life expectancy. For people who have the disease at the time of diagnosis, life expectancy may be shortened depending upon the disease. If a person is diagnosed and treated before serum ferritin is above 1,000ng/mL the risk of cirrhosis or liver cancer is less than 1%.
EXTRA INFORMATION
Mismanaged iron in the brain has been observed in autopsies of people with neuro degenerative diseases: Alzheimer's, early onset Parkinson's, epilepsy, multiple sclerosis, and Huntington's disease.Caucasians are the people most at risk for the classic type of hemochromatosis. More than one million Americans have the genes for this type. However, there are other gene combinations that result in hemochromatosis regardless of a person's ethnicity. It is estimated that as much as or more than 16 million Americans have some degree of elevated iron and are at risk for the same diseases that occur in people with the untreated classic type: bone and joint disease, cirrhosis, liver cancer, diabetes, hypothyroidism, hypogonadism, infertility, impotence, depression, or premature death due to liver or heart failure.
ANAEMIA
![Picture](/uploads/8/0/7/8/80782094/9776218.jpg?250)
DEFINITION
An anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency.
Subtopics of Anaemia:
SIGNS AND SYMPTOMS
Main symptoms that may appear in anemia.Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself. Most commonly, people with anemia report feelings of weakness, or fatigue, general malaise, and sometimes poor concentration. They may also report dyspnea (shortness of breath) on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure. On examination, the signs exhibited may include pallor (pale skin, lining mucosa,conjunctiva and nail beds), but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or legulcers (seen in sickle-cell disease). In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). There may be signs of heart failure. Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in those with iron-deficiency anemia.
CAUSES AND RISK FACTORS
The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency.
Impaired production
Increased destruction
Further information: Hemolytic anemia
Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.
Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:
DIAGNOSIS
Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using amicroscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.
In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.
TREATMENT
Treatments for anemia depend on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace specific deficiencies.
Oral iron
EXTRA INFORMATION
Symptoms of anemia can also cause discomfort. In pregnant women, folate deficiency has been associated with neural tube or spinal defects (such as spina bifida) in the infant.
Other, more severe complications may include:
An anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency.
Subtopics of Anaemia:
- Sickle cell anemia
- Iron-deficiency anemia
- Vitamin deficiency
- Bone marrow and stem cell problems
- Other health conditions
SIGNS AND SYMPTOMS
Main symptoms that may appear in anemia.Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself. Most commonly, people with anemia report feelings of weakness, or fatigue, general malaise, and sometimes poor concentration. They may also report dyspnea (shortness of breath) on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure. On examination, the signs exhibited may include pallor (pale skin, lining mucosa,conjunctiva and nail beds), but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or legulcers (seen in sickle-cell disease). In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). There may be signs of heart failure. Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in those with iron-deficiency anemia.
CAUSES AND RISK FACTORS
The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency.
Impaired production
- Disturbance of proliferation and differentiation of stem cells
- Pure red cell aplasia
- Aplastic anemia affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities.
- Anemia of renal failure by insufficient erythropoietin production
- Anemia of endocrine disorders
- Disturbance of proliferation and maturation of erythroblasts
- Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia
- Anemia of folic acid deficiency, as with vitamin B12, causes megaloblastic anemia
- Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age.
- Iron deficiency anemia, resulting in deficient heme synthesis
- Thalassemias, causing deficient globin synthesis
- Congenital dyserythropoietic anemias, causing ineffective erythropoiesis
- Anemia of renal failure (also causing stem cell dysfunction)
- Other mechanisms of impaired RBC production
- Myelophthisic anemia or myelophthisisis a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas.
- Myelodysplastic syndrome
- Anemia of chronic inflammation
Increased destruction
Further information: Hemolytic anemia
Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.
- Intrinsic (intracorpuscular) abnormalities cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders.
- Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen.
- Hereditary elliptocytosis is another defect in membrane skeleton proteins.
- Abetalipoproteinemia causing defects in membrane lipids
- Enzyme deficiencies
- Pyruvate kinase and hexokinasedeficiencies, causing defectglycolysis
- Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetasedeficiency, causing increased oxidative stress
- Hemoglobinopathies
- Sickle cell anemia
- Hemoglobinopathies causing unstable hemoglobins
- Paroxysmal nocturnal hemoglobinuria
- Extrinsic (extracorpuscular) abnormalities
- Antibody-mediated
- Warm autoimmune hemolytic anemiais caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of theautoimmune hemolytic diseases. It can be idiopathic, that is, without any known cause, drug-associated or secondary to another disease such assystemic lupus erythematosus, or a malignancy, such as chronic lymphocytic leukemia.
- Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition.
- Rh disease, one of the causes of hemolytic disease of the newborn
- Transfusion reaction to blood transfusions
- Mechanical trauma to red cells
- Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation
- Infections, including malaria
- Heart surgery
- Haemodialysis
- Anemia of prematurity from frequent blood sampling for laboratory testing, combined with insufficient RBC production
- Trauma or surgery, causing acute blood loss
- Gastrointestinal tract lesions, causing either acute bleeds (e.g. variceal lesions, peptic ulcers or chronic blood loss (e.g. angiodysplasia)
- Gynecologic disturbances, also generally causing chronic blood loss
- From menstruation, mostly among young women or older women who have fibroids
- Infection by intestinal nematodes feeding on blood, such as hookworms and the whipworm Trichuris trichiura.
Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:
- General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.
- Anemia of pregnancy is induced by blood volume expansion experienced inpregnancy.
DIAGNOSIS
Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using amicroscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.
In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.
TREATMENT
Treatments for anemia depend on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace specific deficiencies.
Oral iron
- Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to suffer from iron deficiency; one-third of them have the more severe form of the disorder, anemia. Iron deficiency from nutritional causes is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of loss, such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate, ferrous fumarate, or ferrous gluconate. When taking iron supplements, stomach upset and/or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit. In anemias of chronic disease, associated with chemotherapy, or associated with renal disease, some clinicians prescribe recombinant erythropoietin or epoetin alfa, to stimulate RBC production, although since there is also concurrent iron deficiency and inflammation present,parenteral iron is advised to be taken concurrently.
- In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively) or where absorption is impeded (for example in cases of inflammation), parenteral iron can be used. The body can absorb up to 6 mg iron daily from the gastrointestinal tract. In many cases the patient has a deficit of over 1,000 mg of iron which would require several months to replace. This can be given concurrently with erythropoietin to ensure sufficient iron for increased rates of erythropoiesis.
- Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80 g/L (6 to 8 g/dL). In those with coronary artery disease who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL). Transfusing earlier does not improve survival. Transfusions otherwise should only be undertaken in cases of cardiovascular instability.
- Erythropoiesis-stimulating agent
- The motive for the administration of an erythropoiesis-stimulating agent (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the individual persons needs. They should not be used for mild or moderate anemia. They are not recommended in people with chronic kidney disease unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron.
- Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen(HBO) by the Undersea and Hyperbaric Medical Society. The use of HBO is indicated when oxygen delivery to tissue is not sufficient in patients who cannot be given blood transfusions for medical or religious reasons. HBO may be used for medical reasons when threat of blood product incompatibility or concern for transmissible disease are factors. The beliefs of some religions (ex:Jehovah's Witnesses) may require they use the HBO method. A 2005 review of the use of HBO in severe anemia found all publications reported positive results.
EXTRA INFORMATION
Symptoms of anemia can also cause discomfort. In pregnant women, folate deficiency has been associated with neural tube or spinal defects (such as spina bifida) in the infant.
Other, more severe complications may include:
- Curly graying hair
- Increased skin color (pigment)
- Infertility
- Worsening of heart disease or heart failure
AMYLOIDOSIS
DEFINITION
Amyloidosis is a rare disease that results from the buildup of misfolded proteins known as amyloids. When proteins that are normally dissolvable in water fold to become amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function. The type of protein that is misfolded and the organ or tissue in which the misfolded proteins are deposited determine the clinical manifestations of amyloidosis.
Subtopics of amyloidosis:
1. AL amyloidosis
2. AA amyloidosis
3. Hereditary amyloidosis
4 ATTR amyloidosis
5. Non-ttr amyloidosis
Amyloidosis is a rare disease that results from the buildup of misfolded proteins known as amyloids. When proteins that are normally dissolvable in water fold to become amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function. The type of protein that is misfolded and the organ or tissue in which the misfolded proteins are deposited determine the clinical manifestations of amyloidosis.
Subtopics of amyloidosis:
1. AL amyloidosis
2. AA amyloidosis
3. Hereditary amyloidosis
4 ATTR amyloidosis
5. Non-ttr amyloidosis
AL AMYLOIDOSIS
DEFINITION
AL amyloidosis is caused by the deposition of light chain proteins produced by plasma cells in different disease states.
SIGNS AND SYMPTOMS
CAUSES AND RISK FACTORS
AL amyloidosis occurs when an abnormality in the plasma cells found in bone marrow (the spongy tissue at the centre of some bones) results in the excessive production of proteins called 'light chains'.Normally, light chains form part of antibodies (proteins that help protect the body from illness and infection), but in cases of AL amyloidosis, large numbers of misfolded light chains are produced and these clump together into thread-like fibres that the body cannot clear away easily.These fibres typically then gradually start to form deposits in the heart, kidneys, nerves, or liver.The abnormal white blood cells in the bone marrow are usually benign (non-cancerous), but some cases of AL amyloidosis are linked to a type of bone marrow cancer called multiple myeloma.
DIAGNOSIS
Diagnosis of AL amyloidosis can be challenging, since the symptoms are often very general.
The diagnosis can be confirmed by removing a biopsy (small tissue sample) from the affected part of the body, and examining this under a microscope in the laboratory, using special stains to check for amyloid proteins.How the tissue sample is removed will depend on which parts of the body are affected. In some people with suspected anyloidosis, a biopsy of tummy fat (taken using a needle) or a biopsy from the gut (taken during an endoscopy) may give a positive result.
TREATMENT
There are currently no treatments available that can directly remove the amyloid deposits associated with AL amyloidosis. Treatment aims to prevent the further production of abnormal light chains while monitoring and treating any problems affecting your organs.
This can give your body enough time to gradually clear the deposits before they build up again and can help prevent organ damage.
In most cases, this will involve having chemotherapy to damage the abnormal bone marrow cells and inhibit production of the abnormal proteins.
You will also need treatment for organ failure – for example, you may need diuretic medication to treat heart failure and you may need dialysis if you have kidney failure.
Some people with kidney failure may be suitable to receive a kidney transplant, although the underlying bone marrow disorder will need to be suppressed by chemotherapy to prevent build-up of amyloid in the new kidney.
After chemotherapy, you will need regular check-ups every six to 12 months to look for signs of the condition returning (relapsing). If it does relapse at any stage, chemotherapy may need to be started again.
AL amyloidosis is caused by the deposition of light chain proteins produced by plasma cells in different disease states.
SIGNS AND SYMPTOMS
- feeling lightheaded or fainting, particularly after standing or sitting up
- numbness or a tingling feeling in the hands and feet (peripheral neuropathy)
- frothy urine
- an irregular heartbeat (arrhythmia)
- chest pain (angina)
- in men, erectile dysfunction
- diarrhoea or constipation
- blood spots on the skin
- carpal tunnel syndrome – compression of the nerve in your wrist
- an enlarged tongue
CAUSES AND RISK FACTORS
AL amyloidosis occurs when an abnormality in the plasma cells found in bone marrow (the spongy tissue at the centre of some bones) results in the excessive production of proteins called 'light chains'.Normally, light chains form part of antibodies (proteins that help protect the body from illness and infection), but in cases of AL amyloidosis, large numbers of misfolded light chains are produced and these clump together into thread-like fibres that the body cannot clear away easily.These fibres typically then gradually start to form deposits in the heart, kidneys, nerves, or liver.The abnormal white blood cells in the bone marrow are usually benign (non-cancerous), but some cases of AL amyloidosis are linked to a type of bone marrow cancer called multiple myeloma.
DIAGNOSIS
Diagnosis of AL amyloidosis can be challenging, since the symptoms are often very general.
The diagnosis can be confirmed by removing a biopsy (small tissue sample) from the affected part of the body, and examining this under a microscope in the laboratory, using special stains to check for amyloid proteins.How the tissue sample is removed will depend on which parts of the body are affected. In some people with suspected anyloidosis, a biopsy of tummy fat (taken using a needle) or a biopsy from the gut (taken during an endoscopy) may give a positive result.
TREATMENT
There are currently no treatments available that can directly remove the amyloid deposits associated with AL amyloidosis. Treatment aims to prevent the further production of abnormal light chains while monitoring and treating any problems affecting your organs.
This can give your body enough time to gradually clear the deposits before they build up again and can help prevent organ damage.
In most cases, this will involve having chemotherapy to damage the abnormal bone marrow cells and inhibit production of the abnormal proteins.
You will also need treatment for organ failure – for example, you may need diuretic medication to treat heart failure and you may need dialysis if you have kidney failure.
Some people with kidney failure may be suitable to receive a kidney transplant, although the underlying bone marrow disorder will need to be suppressed by chemotherapy to prevent build-up of amyloid in the new kidney.
After chemotherapy, you will need regular check-ups every six to 12 months to look for signs of the condition returning (relapsing). If it does relapse at any stage, chemotherapy may need to be started again.
AA AMYLOIDOSIS
DEFINITION
AA amyloidosis is a form of amyloidosis, a disease characterized by the abnormal deposition of fibers of insoluble protein in the extracellular space of various tissues and organs, In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which normally soluble and whose plasma concentration is highest during inflammation.
SIGNS AND SYMPTOMS
AA amyloidosis involves other organs in addition to the kidneys. An enlarged spleen, enlarged liver, and enlarged thyroid are not uncommon. Autonomic neuropathy is frequent with symptoms of orthostatic hypotension (low blood pressure on standing), gastrointestinal atony (slowing of stomach emptying) and diarrhea or constipation. AA amyloid deposits in the heart causing congestive heart failure and arrhythmias (irregular heart beat) may develop later in the course of the disease.Symptoms in a patient with AA amyloidosis can be misunderstood as symptoms that relate to their chronic infection or inflammation. At first, a patient may have symptoms such as weight loss, weakness, and swelling (edema). Since a patient’s primary disorder may also cause these problems, a doctor may assume that these are a result of their primary condition. This can delay further testing which would lead to a diagnosis of the secondary disease, AA amyloidosis.In a reverse situation, AA amyloidosis may be found first, before another disease or condition is identified. For example, AA amyloidosis may be diagnosed as a result of nephrotic syndrome and then may lead to the investigation for an undiagnosed, underlying condition. So, although the AA amyloidosis was triggered by a primary disorder, it does not always mean that the primary disorder was previously discovered and diagnosed.
CAUSES AND RISK FACTORS
Both infectious and noninfectious diseases have been associated with AA amyloidosis. Chronic infectious diseases that have been associated with AA amyloidosis include the following:
RA is the most common rheumatic cause of AA amyloidosis. However, most patients with RA do not have development of AA amyloidosis. Prolonged duration of disease, continuous disease activity, and inadequate treatment are risk factors for AA amyloidosis. Renal failure due to amyloid deposition usually occurs in the fifth decade of life. In living patients with RA, the incidence of AA found on biopsies ranges from 7-29%.
In industrialized countries, chronic noninfectious inflammatory diseases are more commonly the cause of AA amyloidosis. In RA, the incidence is 5-26%, being found more often on autopsy than biopsy. The frequency of AA amyloidosis may be lower in patients treated earlier and more aggressively.
Other inflammatory disorders associated with AA amyloidosis include the following:
AA amyloidosis is a rare complication of inflammatory bowel disease and occurs more commonly in Crohn disease and in males. The reason that Crohn disease is more readily complicated by AA amyloidosis than ulcerative colitis is not known but may be secondary to greater degree of sustained inflammation in association with the former and, in particular, the suppurative features of Crohn disease such as abscesses and fistulae may be risk factors.
DIAGNOSIS
If a patient has previously been diagnosed with a chronic inflammatory disease or chronic infection and they develop high levels of protein in the urine or other associated AA symptoms, then the physician should test for AA amyloid deposition. When renal damage occurs, it can be clinically shown as proteinuria (protein found in the urine), nephrotic syndrome, or impairment of renal (kidney) function. A test involving a 24-hour urine collection can be performed to look at the level of protein in the patient’s urine sample. Protein in the urine is an indication of kidney complications. If amyloidosis is suspected through this and other test results and associated symptoms, in most cases a biopsy of renal (kidney) tissue is recommended to get an accurate diagnosis. This renal biopsy tissue is sent to a lab for Congo-red staining. The lab will stain the biopsy and, if it turns an apple green color under a ‘polarizing’ microscope, then amyloidosis is confirmed. Once this initial diagnosis has been determined, it is very important to find out the exact protein type in a positive tissue biopsy so that appropriate treatment can be recommended. In order to identify the amyloid type, the most common diagnostic test is staining the tissue sample with antibodies that are specific for the major amyloid protein diseases, such as “anti-AA serum,” AL light chains, and anti-TTR. If it is the anti-AA serum result that is positive in this lab test, then AA amyloidosis is diagnosed. It is important to rule out other types because other amyloid diseases may involve the kidneys and those patients may also present with a high level of protein in their urine. However, another type of amyloid disease that is known for kidney involvement, such as AL amyloidosis, would require a different treatment regimen. Once AA amyloidosis is confirmed it is important to look for the primary underlying inflammatory condition, if not already known. Then, the next step is to determine the extent of amyloid involvement in all organs and develop a plan for treatment. This is done by a careful physical examination, and laboratory studies of kidney and heart function.
TREATMENT
Each amyloidosis type has a specific treatment. Early detection and timely treatment is a key factor. The type of treatment is based upon disease progression and seriousness of the patient’s organ, tissue and/or nerve involvement.
AA amyloidosis treatment plans include:
Other new medications will undoubtedly be coming along. Staying in touch with the Amyloidosis Research Consortium and their clinical trial finder will enable patients to be aware of new medications and clinical trials.
AA amyloidosis is a form of amyloidosis, a disease characterized by the abnormal deposition of fibers of insoluble protein in the extracellular space of various tissues and organs, In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which normally soluble and whose plasma concentration is highest during inflammation.
SIGNS AND SYMPTOMS
AA amyloidosis involves other organs in addition to the kidneys. An enlarged spleen, enlarged liver, and enlarged thyroid are not uncommon. Autonomic neuropathy is frequent with symptoms of orthostatic hypotension (low blood pressure on standing), gastrointestinal atony (slowing of stomach emptying) and diarrhea or constipation. AA amyloid deposits in the heart causing congestive heart failure and arrhythmias (irregular heart beat) may develop later in the course of the disease.Symptoms in a patient with AA amyloidosis can be misunderstood as symptoms that relate to their chronic infection or inflammation. At first, a patient may have symptoms such as weight loss, weakness, and swelling (edema). Since a patient’s primary disorder may also cause these problems, a doctor may assume that these are a result of their primary condition. This can delay further testing which would lead to a diagnosis of the secondary disease, AA amyloidosis.In a reverse situation, AA amyloidosis may be found first, before another disease or condition is identified. For example, AA amyloidosis may be diagnosed as a result of nephrotic syndrome and then may lead to the investigation for an undiagnosed, underlying condition. So, although the AA amyloidosis was triggered by a primary disorder, it does not always mean that the primary disorder was previously discovered and diagnosed.
CAUSES AND RISK FACTORS
Both infectious and noninfectious diseases have been associated with AA amyloidosis. Chronic infectious diseases that have been associated with AA amyloidosis include the following:
- Tuberculosis
- Leprosy
- Bronchiectasis
- Chronic osteomyelitis
- Chronic pyelonephritis
RA is the most common rheumatic cause of AA amyloidosis. However, most patients with RA do not have development of AA amyloidosis. Prolonged duration of disease, continuous disease activity, and inadequate treatment are risk factors for AA amyloidosis. Renal failure due to amyloid deposition usually occurs in the fifth decade of life. In living patients with RA, the incidence of AA found on biopsies ranges from 7-29%.
In industrialized countries, chronic noninfectious inflammatory diseases are more commonly the cause of AA amyloidosis. In RA, the incidence is 5-26%, being found more often on autopsy than biopsy. The frequency of AA amyloidosis may be lower in patients treated earlier and more aggressively.
Other inflammatory disorders associated with AA amyloidosis include the following:
- Inflammatory bowel disease (0.4-2%)
- Behçet syndrome in Turkey (1-2%)
- Reactive arthritis in adults (0.3%)
- Psoriatic arthritis (3-13%)
AA amyloidosis is a rare complication of inflammatory bowel disease and occurs more commonly in Crohn disease and in males. The reason that Crohn disease is more readily complicated by AA amyloidosis than ulcerative colitis is not known but may be secondary to greater degree of sustained inflammation in association with the former and, in particular, the suppurative features of Crohn disease such as abscesses and fistulae may be risk factors.
DIAGNOSIS
If a patient has previously been diagnosed with a chronic inflammatory disease or chronic infection and they develop high levels of protein in the urine or other associated AA symptoms, then the physician should test for AA amyloid deposition. When renal damage occurs, it can be clinically shown as proteinuria (protein found in the urine), nephrotic syndrome, or impairment of renal (kidney) function. A test involving a 24-hour urine collection can be performed to look at the level of protein in the patient’s urine sample. Protein in the urine is an indication of kidney complications. If amyloidosis is suspected through this and other test results and associated symptoms, in most cases a biopsy of renal (kidney) tissue is recommended to get an accurate diagnosis. This renal biopsy tissue is sent to a lab for Congo-red staining. The lab will stain the biopsy and, if it turns an apple green color under a ‘polarizing’ microscope, then amyloidosis is confirmed. Once this initial diagnosis has been determined, it is very important to find out the exact protein type in a positive tissue biopsy so that appropriate treatment can be recommended. In order to identify the amyloid type, the most common diagnostic test is staining the tissue sample with antibodies that are specific for the major amyloid protein diseases, such as “anti-AA serum,” AL light chains, and anti-TTR. If it is the anti-AA serum result that is positive in this lab test, then AA amyloidosis is diagnosed. It is important to rule out other types because other amyloid diseases may involve the kidneys and those patients may also present with a high level of protein in their urine. However, another type of amyloid disease that is known for kidney involvement, such as AL amyloidosis, would require a different treatment regimen. Once AA amyloidosis is confirmed it is important to look for the primary underlying inflammatory condition, if not already known. Then, the next step is to determine the extent of amyloid involvement in all organs and develop a plan for treatment. This is done by a careful physical examination, and laboratory studies of kidney and heart function.
TREATMENT
Each amyloidosis type has a specific treatment. Early detection and timely treatment is a key factor. The type of treatment is based upon disease progression and seriousness of the patient’s organ, tissue and/or nerve involvement.
AA amyloidosis treatment plans include:
- Underlying disease treatment – continual management of the primary disease;
- Supportive treatment – treating patient symptoms and organ damage; and,
- Amyloid source treatment, when available – slowing down, or stopping, the overproduction of amyloid at the source of this secondary disease.
- In AA amyloidosis, the most important therapy is to treat the underlying infection or inflammation in order to reduce the level of SAA protein, the precursor for the AA amyloid deposits. These treatments will vary depending on the underlying condition. The effectiveness of this treatment can be monitored by blood tests that measure inflammation in the blood, such as sedimentation rate and C-reactive protein levels. Some treatments that exist for inflammatory diseases could include surgery on the infection or tumor; drug therapies for rheumatoid arthritis; antibiotics for chronic infection; and the use of colchicine for FMF (Familial Mediterranean Fever), among others.
- With effective treatment of the underlying inflammation amyloid deposits have been known to reduce and nephrotic syndrome can improve. However, if the kidney function has become significantly impaired, it rarely recovers.
- Supportive treatment is very important for patients with AA amyloidosis. A team of specialists, including a nephrologist, cardiologist, and neurologist in addition to the primary physician is helpful to manage the disease development in the various organ systems.
- Kidney damage is often a major health issue associated with AA amyloidosis. Regular blood and urine tests are recommended to monitor the patient’s renal (kidney) function. Managing proteinuria (protein in the urine) and nephrotic syndrome and keeping renal function from declining can delay the need for dialysis and improve the quality of life. Under the close supervision of the doctor, the supportive treatment that is often helpful for nephrotic syndrome includes an increase of protein in the diet, monitoring salt intake, and use of support hose. Other things that are very important when the kidney has amyloid deposits are maintaining normal blood pressure and avoiding dehydration.
- It is important to note that the patient should not take any medication (prescription or over the counter) unless it has been approved by the nephrologist. When the kidney already has some damage, some medications can worsen this kidney damage. It can happen even when these same medications would be acceptable for normal kidneys. Therefore, it is very important that all patients with AA amyloidosis and renal involvement have a nephrologist on their medical team.
- Dialysis is an option for patients with AA amyloidosis that are in renal failure, especially when other organ function is in good condition. A kidney transplant is an option in some cases, particularly if the associated inflammatory disease or chronic infection has been treated successfully.
- Supportive treatment for autonomic neuropathy includes maintaining blood pressure when standing by using support hose, along with a slight increase of salt in the diet or medications that raise blood pressure.
- Symptoms of gastric distress may be harder to manage, but frequent small meals and a diet lower in fat are often helpful. Medications can be used for diarrhea. An adjustment of the patient’s meal timing can also ease the onset of diarrhea.
- Cardiac involvement needs to be watched closely by a cardiologist to manage treatment for congestive heart failure or arrhythmia.
- There is currently a new drug in development that is in the final phase of clinical trials. It is not a treatment for the primary, underlying chronic inflammatory disease or chronic infection. It targets AA amyloidosis. The medicine works by interfering with the AA portion of the SAA molecule, preventing it from depositing in tissues. This therapy for AA amyloidosis can help to prevent organ damage and delay the need for dialysis.
Other new medications will undoubtedly be coming along. Staying in touch with the Amyloidosis Research Consortium and their clinical trial finder will enable patients to be aware of new medications and clinical trials.
HEREDITARY AMYLOIDOSIS
DEFINITION
Hereditary amyloidosis is one type of the systemic amyloidosis diseases that are caused by inheriting a gene mutation. That genetic mutation then produces an amyloid protein that forms into an abnormal shape. These abnormal “misfolded” amyloid proteins can be deposited and cluster in the body’s nerves and other organs and once they build up, this may affect and harm tissue and/or organ function. Even though you are born with a gene mutation, normally the harmful deposits don’t occur until adulthood. Although all the types of the hereditary amyloidoses can cause serious complications, there are some carriers of this genetic mutation that may not show symptoms of the disease at all. Others may have a few, more minor, health issues.
SIGNS AND SYMPTOMS
CAUSES AND RISK FACTORS
Affects the liver, nerves, heart and kidneys. One type is caused by a certain amyloid (transthyretin amyloid) that can affect the nervous system or the heart. African-Americans have a greater risk of this type than do Caucasians. It is thought to be a significant cause of heart failure in African-American men.
Anyone can develop amyloidosis. Factors that increase your risk include:
DIAGNOSIS
The diagnosis of hereditary amyloidosis was made by kidney biopsy in 64 patients and by serum amyloid P component (SAP) scintigraphy in conjunction with genetic analysis in the context of renal dysfunction and a known family history of AFib in seven patients. The renal histologic appearance in every patient was characteristic and showed striking glomerular enlargement with almost complete obliteration of the normal glomerular architecture by extensive amyloid deposition. In contrast, the vessels and renal tubular interstitium of every such patient contained almost no amyloid at all. Definitive immunohistochemical staining of the amyloid with an antibody against fibrinogen Aα-chain was achieved in 93% of patients, whereas staining was absent in all patients with a panel of antibodies directed against serum amyloid A protein (SAA), kappa and lambda Ig light chains, and apoAI. Although immunohistochemical staining with the anti-fibrinogen antibody was not definitive in 7% of patients, every such patient had a previously reported amyloidogenic fibrinogen mutation, the same characteristic renal morphology, and an overall clinical picture and disease course that was completely typical for AFib. None of these patients had an inflammatory disease or a plasma cell dyscrasia to suggest secondary (AA) or primary (AL) amyloidosis, respectively, or a mutation in any of the other genes that encode known amyloid fibril proteins including apoAI, apoAII, and lysozyme/
TREATMENT
Supportive Treatment
Hereditary amyloidosis is one type of the systemic amyloidosis diseases that are caused by inheriting a gene mutation. That genetic mutation then produces an amyloid protein that forms into an abnormal shape. These abnormal “misfolded” amyloid proteins can be deposited and cluster in the body’s nerves and other organs and once they build up, this may affect and harm tissue and/or organ function. Even though you are born with a gene mutation, normally the harmful deposits don’t occur until adulthood. Although all the types of the hereditary amyloidoses can cause serious complications, there are some carriers of this genetic mutation that may not show symptoms of the disease at all. Others may have a few, more minor, health issues.
SIGNS AND SYMPTOMS
- Nervous system disorders
- Gastrointestinal conditions, such as diarrhea and weight loss
- Heart problems
- Carpal tunnel syndrome
- Kidney disease, though this is less common than in AL
CAUSES AND RISK FACTORS
Affects the liver, nerves, heart and kidneys. One type is caused by a certain amyloid (transthyretin amyloid) that can affect the nervous system or the heart. African-Americans have a greater risk of this type than do Caucasians. It is thought to be a significant cause of heart failure in African-American men.
Anyone can develop amyloidosis. Factors that increase your risk include:
- Age. Most people diagnosed with AL amyloidosis, the most common type, are age 50 or older, although earlier onset occurs.
- Gender. Nearly 70 percent of people with AL amyloidosis are men.
- Other diseases. Having a chronic infectious or inflammatory disease increases your risk of AA amyloidosis.
- Family history. Some types of amyloidosis are hereditary.
- Kidney dialysis. Dialysis can't always remove large proteins from the blood. If you're on dialysis, abnormal proteins can build up in your blood and eventually be deposited in tissue. This condition is less common with modern dialysis techniques.
DIAGNOSIS
The diagnosis of hereditary amyloidosis was made by kidney biopsy in 64 patients and by serum amyloid P component (SAP) scintigraphy in conjunction with genetic analysis in the context of renal dysfunction and a known family history of AFib in seven patients. The renal histologic appearance in every patient was characteristic and showed striking glomerular enlargement with almost complete obliteration of the normal glomerular architecture by extensive amyloid deposition. In contrast, the vessels and renal tubular interstitium of every such patient contained almost no amyloid at all. Definitive immunohistochemical staining of the amyloid with an antibody against fibrinogen Aα-chain was achieved in 93% of patients, whereas staining was absent in all patients with a panel of antibodies directed against serum amyloid A protein (SAA), kappa and lambda Ig light chains, and apoAI. Although immunohistochemical staining with the anti-fibrinogen antibody was not definitive in 7% of patients, every such patient had a previously reported amyloidogenic fibrinogen mutation, the same characteristic renal morphology, and an overall clinical picture and disease course that was completely typical for AFib. None of these patients had an inflammatory disease or a plasma cell dyscrasia to suggest secondary (AA) or primary (AL) amyloidosis, respectively, or a mutation in any of the other genes that encode known amyloid fibril proteins including apoAI, apoAII, and lysozyme/
TREATMENT
Supportive Treatment
- Supportive treatment is helpful for various symptoms, including peripheral neuropathy, autonomic neuropathy, and cardiac and kidney problems, and can change the quality of life for many people. There are several medications that can be prescribed to treat peripheral neuropathy, which can cause tingling or burning in some parts of the body. These medications can help with pain relief and nerve damage. If a patient has autonomic neuropathy, symptoms can vary, with common problems affecting blood pressure, heart rate, digestion, and perspiration, depending on the location of the damage to the nerves. Other gastrointestinal dysfunctions may require treatment for symptoms that include poor nutritional health, diarrhea or constipation, and nausea or vomiting. Doctors can prescribemedications to help with these symptoms to lessen the pain and the symptom itself.Management of heart problems, heart failure, and kidney dialysis (when needed) make a significant improvement on a patient’s quality of life. Reversing any damage to the organs and other parts of the body is difficult to achieve. If treatment begins during the early onset of clinical symptoms, the overall success rate is higher, so early detection is essential.
ATTR AMYLOIDOSIS
DEFINITION
ATTR amyloidosis means A for Amyloid and the TTR is short for the protein “transthyretin.” ATTR is one term that represents different kinds of mutations in a TTR gene that is inherited. That gene mutation makes the transthyretin unstable, so amyloid protein misfolding occurs. The amyloid fibrils then go out into the body and can damage nerves and/or organs, depending on the type of TTR mutation that the patient has inherited. TTR is mainly manufactured in the liver.
SIGNS AND SYMPTOMS
If a patient has a clear family history along with clinical signs of amyloidosis, then ATTR is highly possible. However, there are times when someone is the first case to be identified in his or her family. Since many amyloidosis and other diseases can cause similar symptoms, it is vital that the patient is diagnosed properly with the type of amyloid protein clearly identified.
Symptoms of ATTR vary, depending on the TTR genetic variant that is involved and the organ (or multiple organs) that demonstrate signs of amyloid deposition. The most common sites of amyloid deposits are associated with cardiac and/or nerve involvement (called cardiomyopathy and neuropathy) and the gastrointestinal tract. The kidneys, eyes, and carpal ligament (also known as carpal tunnel syndrome) are among other possibilities that can be affected.
For each patient, the symptoms will depend on which organs are affected by the amyloid deposits. It also depends on the degree that the organ function is impaired.
The Heart
When amyloid deposits cause cardiomyopathy, it can result in a stiffening of the heart. Some patients may experience:
• Nausea
• Weight loss
• Inability to sleep
• Increasing fatigue
• Dizziness
• Shortness of breath
• Leg swelling (edema)
• Palpitations and abnormal heart rhythms (atrial fibrillation)
• Chest pain.
Congestive heart failure and atrial fibrillation are the most common symptoms. The term “arrhythmia” refers to changes in the normal electrical impulses that cause the heart to beat. The result is a heart that can beat too fast, too slow or erratically. Atrial fibrillation (or a-fib for short) is one of the many forms of arrhythmia. During a-fib, the heart’s two small upper chambers cause an abnormal heart rhythm, usually rapid and irregular beating. This may result in increased heart damage, stroke or heart failure.
CAUSES AND RISK FACTORS
ATTR amyloidosis is caused by amyloid deposits made up of a proteincalled transthyretin (TTR). There are three distinct different types of ATTR amyloidosis:
“trans-thy-retin”. People with mutations in the TTR gene produce abnormal,amyloidogenic, “variant” TTR throughout their lives.
Amyloid deposits consisting of abnormal “variant” TTR may cause:
DIAGNOSIS
First, a patient is tested to determine if they have amyloid proteins in their body. If amyloidosis is confirmed but the type is not clearly found in these tests, it will be important to do more tests to find the exact type and also to determine the variation of ATTR. The main diagnostic testing for any amyloidosis disease includes blood tests, urine tests and biopsies. Some tests are only done once to confirm a diagnosis, while others may be repeated to monitor the disease and response to therapy. Blood and urine tests will be done to help your doctor determine the diagnosis of amyloidosis. These tests can also help to show which organs are involved and how much damage they may have. In addition, a tissue biopsy will be performed. This involves the removal of a small sample of tissue for lab examination. A tissue sample is essential to confirm the diagnosis and type of amyloidosis. A “Congo red stain” is put on the biopsy tissue and if the lab examiner then sees the light wave change to an apple green color (called “birefringence”) then amyloidosis is diagnosed. With ATTR, after amyloidosis is confirmed and it is determined that there is transthyretin amyloid protein (via biopsy and Congo red staining in the lab), the protein needs to be identified by protein sequence analysis and DNA sequencing must be performed. When scientists examine your blood for certain genetic markers it is called genome sequencing. A simple blood sample is sent to a lab and experts examine the DNA chains. If a certain condition is in question, then sections of the DNA chain will be checked for genetic markers of the condition or defect. Since the hereditary amyloidosis variations affect individuals differently, it is important to establish which variation you have in order to identify a treatment plan that is tailored for your type of amyloidosis. The DNA sequence analysis of TTR identifies more than 99% of disease-causing mutations. A person should never ignore any health problem. Early detection can be important with any disease and the more tests that are done, the more accurate the diagnosis.
TREATMENT
Source Treatment
ATTR amyloidosis means A for Amyloid and the TTR is short for the protein “transthyretin.” ATTR is one term that represents different kinds of mutations in a TTR gene that is inherited. That gene mutation makes the transthyretin unstable, so amyloid protein misfolding occurs. The amyloid fibrils then go out into the body and can damage nerves and/or organs, depending on the type of TTR mutation that the patient has inherited. TTR is mainly manufactured in the liver.
SIGNS AND SYMPTOMS
If a patient has a clear family history along with clinical signs of amyloidosis, then ATTR is highly possible. However, there are times when someone is the first case to be identified in his or her family. Since many amyloidosis and other diseases can cause similar symptoms, it is vital that the patient is diagnosed properly with the type of amyloid protein clearly identified.
Symptoms of ATTR vary, depending on the TTR genetic variant that is involved and the organ (or multiple organs) that demonstrate signs of amyloid deposition. The most common sites of amyloid deposits are associated with cardiac and/or nerve involvement (called cardiomyopathy and neuropathy) and the gastrointestinal tract. The kidneys, eyes, and carpal ligament (also known as carpal tunnel syndrome) are among other possibilities that can be affected.
For each patient, the symptoms will depend on which organs are affected by the amyloid deposits. It also depends on the degree that the organ function is impaired.
The Heart
When amyloid deposits cause cardiomyopathy, it can result in a stiffening of the heart. Some patients may experience:
• Nausea
• Weight loss
• Inability to sleep
• Increasing fatigue
• Dizziness
• Shortness of breath
• Leg swelling (edema)
• Palpitations and abnormal heart rhythms (atrial fibrillation)
• Chest pain.
Congestive heart failure and atrial fibrillation are the most common symptoms. The term “arrhythmia” refers to changes in the normal electrical impulses that cause the heart to beat. The result is a heart that can beat too fast, too slow or erratically. Atrial fibrillation (or a-fib for short) is one of the many forms of arrhythmia. During a-fib, the heart’s two small upper chambers cause an abnormal heart rhythm, usually rapid and irregular beating. This may result in increased heart damage, stroke or heart failure.
CAUSES AND RISK FACTORS
ATTR amyloidosis is caused by amyloid deposits made up of a proteincalled transthyretin (TTR). There are three distinct different types of ATTR amyloidosis:
- Familial amyloid polyneuropathy (FAP) (hereditary – runs in families and can overlap with FAC)
- Familial amyloid cardiomyopathy (FAC) (hereditary – runs in families and can overlap with FAP)
- Senile systemic amyloidosis or wild-type ATTR amyloidosis (not hereditary – does not run in families or cause polyneuropathy).
“trans-thy-retin”. People with mutations in the TTR gene produce abnormal,amyloidogenic, “variant” TTR throughout their lives.
Amyloid deposits consisting of abnormal “variant” TTR may cause:
- Familial amyloid polyneuropathy (FAP). This disease affects the nervous system, often the heart and sometimes the kidneys and eyes. It is very rare, with the commonest type, associated with the Val30Met mutation thought to affect about 10,000 people in the whole world. It has hitherto clearly been by far the most commonly recognised form of hereditary systemic amyloidosis.
- Familial Amyloid cardiomyopathy (FAC) (heart disease), most commonly in men over age 60 of African American ancestry. There is often carpal tunnel syndrome but other organs are not affected. This condition has only been recognised recently and is probably common in this population and widely underdiagnosed.
DIAGNOSIS
First, a patient is tested to determine if they have amyloid proteins in their body. If amyloidosis is confirmed but the type is not clearly found in these tests, it will be important to do more tests to find the exact type and also to determine the variation of ATTR. The main diagnostic testing for any amyloidosis disease includes blood tests, urine tests and biopsies. Some tests are only done once to confirm a diagnosis, while others may be repeated to monitor the disease and response to therapy. Blood and urine tests will be done to help your doctor determine the diagnosis of amyloidosis. These tests can also help to show which organs are involved and how much damage they may have. In addition, a tissue biopsy will be performed. This involves the removal of a small sample of tissue for lab examination. A tissue sample is essential to confirm the diagnosis and type of amyloidosis. A “Congo red stain” is put on the biopsy tissue and if the lab examiner then sees the light wave change to an apple green color (called “birefringence”) then amyloidosis is diagnosed. With ATTR, after amyloidosis is confirmed and it is determined that there is transthyretin amyloid protein (via biopsy and Congo red staining in the lab), the protein needs to be identified by protein sequence analysis and DNA sequencing must be performed. When scientists examine your blood for certain genetic markers it is called genome sequencing. A simple blood sample is sent to a lab and experts examine the DNA chains. If a certain condition is in question, then sections of the DNA chain will be checked for genetic markers of the condition or defect. Since the hereditary amyloidosis variations affect individuals differently, it is important to establish which variation you have in order to identify a treatment plan that is tailored for your type of amyloidosis. The DNA sequence analysis of TTR identifies more than 99% of disease-causing mutations. A person should never ignore any health problem. Early detection can be important with any disease and the more tests that are done, the more accurate the diagnosis.
TREATMENT
Source Treatment
- For most ATTR variations, the liver is the main source of amyloid production. However, the liver itself is not affected by the disease in most cases and the amyloid burden causes damage in other parts of the body. A liver transplant is very helpful in reducing (or stopping) the amyloid deposits. It can stabilize or improve neurological symptoms as well as gastrointestinal problems (which can correct poor nutrition and overall health). However, the statistics vary as to who can benefit from these transplants, with the more common ATTR Val30Met having the highest success rate. The outcome of liver transplantation is largely dependent on the mutation that exists in the patient. In some cases, amyloid deposition does completely stop after transplantation, so research is ongoing in this area. For those patients with cardiac symptoms, studies have shown that heart problems may continue after a liver transplant. In some situations, a combined heart and liver transplant will help a patient with an ATTR variant that produces advanced cardiac problems. In clinical trials, new therapies aim to control TTR tetramers and avoid amyloid fibril formation. Ongoing trials include studies with the compounds diflunisal and tafamidis. Several other pharmaceutical companies are testing strategies that cause a decrease in the production of TTR protein. There have been advances in research that are studying the ‘silencing’ of gene expression through the addition of stranded RNA. This is called RNAi (meaning RNA interference). New medications are in development that include RNAi therapy, targeting transthyretin (TTR). Advances in treatment are likely, with new studies and clinical trials currently in view. It is possible that ATTR can cause serious health complications, so it should not be taken lightly. However, do not assume that disability or severe health issues are stamped on your future. There are treatments available and research continues.
NON-TTR AMYLOIDOSIS
DEFINITION
These diseases are considered even more rare than the ATTR variations. The Non-TTR amyloidoses consist of other inherited gene mutations that can also cause major symptoms and affect your health. These proteins are Apo lipoprotein AI, Fibrinogen Aa, Lysozyme, Apo lipoprotein AII, Gelsolin, and Cystatin C. More variations may be discovered as research continues.
SIGNS AND SYMPTOMS
Non-TTR symptoms can vary with each mutation, including problems with the kidneys, liver, heart or peripheral neuropathy. Some mutations have symptoms that involve the brain or the eye.
Each individual can present with different clinical symptoms. The symptoms, as well as the prognosis, depend on the tissue and organ(s) affected by the amyloid deposits. Although all the hereditary amyloidoses may cause serious complications for some individuals, there are some carriers of genetic mutations that may not show symptoms of the disease at all. Others may have a few, more minor, health issues.
Like ATTR, there are numerous variations within the protein identification.
DIAGNOSIS
First, a patient is tested to determine if they have amyloid proteins in their body. If amyloidosis is confirmed but the type is not clearly found in these tests, it will be important to do more tests to find the exact type and also to determine the variation of Non-TTR amyloidosis. The main diagnostic testing for any amyloidosis disease is made up of blood tests, urine tests and biopsies. Some tests are only done once to confirm a diagnosis, while others may be repeated to monitor the disease and response to therapy. Blood and urine tests will be done to help your doctor determine the diagnosis of amyloidosis. These tests can also help to show which organs are involved and how much damage they may have. In addition, a tissue biopsy will be performed. This involves the removal of a small sample of tissue for lab examination. A tissue sample is essential to confirm the diagnosis and type of amyloidosis. A “Congo red stain” is put on the biopsy tissue and if the lab examiner then sees the light wave change to an apple green color (called “birefringence”) then amyloidosis is diagnosed. With Non-TTR, after amyloidosis is confirmed and it is determined that there is amyloid protein (via biopsy and Congo red staining in the lab), the protein needs to be identified by protein sequence analysis and DNA sequencing must be performed. When scientists examine your blood for certain genetic markers it is called genome sequencing. A simple blood sample is sent to a lab and experts examine the DNA chains. If a certain condition is in question, then sections of the DNA chain will be checked for genetic markers of the condition or defect. Since these hereditary variations affect individuals differently, it is important to establish which variation you have in order to identify a treatment plan that is tailored for your type of amyloidosis. The genome sequencing does this. With the Non-TTR Amyloidosis diseases (AFib, ApoA1, ApoA2, ALys, etc.), it is highly recommended that the genome sequencing be performed or reviewed by one of the specialty amyloidosis centers in order to identify and verify the correct diagnosis. A person should never ignore any health problem. Early detection can be important with any disease and the more tests that are done, the more accurate the diagnosis.
TREATMENT
EXTRA INFORMATION
Amyloidosis has been labeled as a rare disease by the U.S. Office of Rare Diseases (ORD), which is a segment of the National Institutes of Health (NIH). It is also referred to as an “orphan” disease. As a classified rare disease by the U.S. government, this means that it is estimated that all of the types of Amyloidosis combined affects less than 200,000 people in the U.S. population.As research continues, this rare classification may change. Many experts suspect that some of the amyloidosis diseases are not that rare — just rarely diagnosed. As funding increases for research, our understanding of the amyloid diseases will lead us in new directions.A major challenge is the current lack of early diagnosis for a patient with amyloidosis. This is a key factor. Awareness of all the amyloidosis diseases by the medical community and by the general public is essential in order to turn this around.
These diseases are considered even more rare than the ATTR variations. The Non-TTR amyloidoses consist of other inherited gene mutations that can also cause major symptoms and affect your health. These proteins are Apo lipoprotein AI, Fibrinogen Aa, Lysozyme, Apo lipoprotein AII, Gelsolin, and Cystatin C. More variations may be discovered as research continues.
SIGNS AND SYMPTOMS
Non-TTR symptoms can vary with each mutation, including problems with the kidneys, liver, heart or peripheral neuropathy. Some mutations have symptoms that involve the brain or the eye.
Each individual can present with different clinical symptoms. The symptoms, as well as the prognosis, depend on the tissue and organ(s) affected by the amyloid deposits. Although all the hereditary amyloidoses may cause serious complications for some individuals, there are some carriers of genetic mutations that may not show symptoms of the disease at all. Others may have a few, more minor, health issues.
Like ATTR, there are numerous variations within the protein identification.
- Apolipoprotein AI – 22 known variations with differing symptoms, including amyloid deposit involvement in the kidneys, liver, heart, peripheral neuropathy, cutaneous (skin) areas, and laryngeal (larynx).
- Fibrinogen Aa – 14 variations with symptoms that only involve the kidneys, with 1 also involving neuropathy.
- Lysozyme – 7 variations that involve kidney and/or liver symptoms, with 1 also involving the GI tract.
- Apolipoprotein AII – 5 variations that involve kidney symptoms only.
- Gelsolin – 4 variations with peripheral neuropathy symptoms, 1 also involving the eye.
- Cystatin C – 1 variation with cerebral hemorrhage complications.
DIAGNOSIS
First, a patient is tested to determine if they have amyloid proteins in their body. If amyloidosis is confirmed but the type is not clearly found in these tests, it will be important to do more tests to find the exact type and also to determine the variation of Non-TTR amyloidosis. The main diagnostic testing for any amyloidosis disease is made up of blood tests, urine tests and biopsies. Some tests are only done once to confirm a diagnosis, while others may be repeated to monitor the disease and response to therapy. Blood and urine tests will be done to help your doctor determine the diagnosis of amyloidosis. These tests can also help to show which organs are involved and how much damage they may have. In addition, a tissue biopsy will be performed. This involves the removal of a small sample of tissue for lab examination. A tissue sample is essential to confirm the diagnosis and type of amyloidosis. A “Congo red stain” is put on the biopsy tissue and if the lab examiner then sees the light wave change to an apple green color (called “birefringence”) then amyloidosis is diagnosed. With Non-TTR, after amyloidosis is confirmed and it is determined that there is amyloid protein (via biopsy and Congo red staining in the lab), the protein needs to be identified by protein sequence analysis and DNA sequencing must be performed. When scientists examine your blood for certain genetic markers it is called genome sequencing. A simple blood sample is sent to a lab and experts examine the DNA chains. If a certain condition is in question, then sections of the DNA chain will be checked for genetic markers of the condition or defect. Since these hereditary variations affect individuals differently, it is important to establish which variation you have in order to identify a treatment plan that is tailored for your type of amyloidosis. The genome sequencing does this. With the Non-TTR Amyloidosis diseases (AFib, ApoA1, ApoA2, ALys, etc.), it is highly recommended that the genome sequencing be performed or reviewed by one of the specialty amyloidosis centers in order to identify and verify the correct diagnosis. A person should never ignore any health problem. Early detection can be important with any disease and the more tests that are done, the more accurate the diagnosis.
TREATMENT
- Supportive treatment – treating your symptoms and organ
damage; and, - Source treatment – slowing down, or stopping, the overproduction of amyloid at the source of the disease.
- Supportive treatment can vary with each mutation of the non-TTR diseases, however, many of them present with kidney or heart damage, so organ transplantation has been used in these cases with success. Although not a cure, and even if production of the variant amyloid protein continues, an organ transplant can slow the progression of the disease, improve quality of life and prolong survival significantly.
- Liver transplants are less of a source treatment option for most of the Non-TTR amyloidosis diseases. However, Fibrinogen is one variation that has amyloid production occurring solely in the liver, so a liver transplant can slow, or stop, amyloid production at the source. Often, a kidney transplant is also performed because kidney damage is the main target of this disease. So, transplants of both these organs can provide a successful supportive (kidney), and source (liver), treatment in this Fibrinogen variation.
- Lysozyme, Apo lipoprotein A-I and AII, along with the other Non-TTR variations, are so varied that you should consult with a specialist at an amyloid center to recommend a treatment for your individual needs. Source treatments for the hereditary Non-TTR amyloidosis variants are not as advanced as they are for ATTR. These types are more rare and seem to progress slowly.
- Current organ transplants and other treatments include:
- Apolipoprotein AI
- Supportive Treatment Possibilities (affected organ) –
kidney and/or heart transplant, depending on organ damage - Source Treatment (to reduce amyloid production) – liver transplant
- Supportive Treatment Possibilities (affected organ) –
kidney transplant - Source Treatment (to reduce amyloid production) – liver transplant
- Supportive Treatment Possibilities (affected organ) –
kidney and/or liver transplant, depending on organ damage - Source Treatment (to reduce amyloid production) – none at this time
- Supportive Treatment Possibilities (affected organ) –
kidney transplant - Source Treatment (to reduce amyloid production) – none at this time
- Supportive Treatment Possibilities (affected organ) –
cornea transplant - Source Treatment (to reduce amyloid production) – none at this time
- Supportive Treatment Possibilities – avoid fever
- Source Treatment (to reduce amyloid production) – none at this time
EXTRA INFORMATION
Amyloidosis has been labeled as a rare disease by the U.S. Office of Rare Diseases (ORD), which is a segment of the National Institutes of Health (NIH). It is also referred to as an “orphan” disease. As a classified rare disease by the U.S. government, this means that it is estimated that all of the types of Amyloidosis combined affects less than 200,000 people in the U.S. population.As research continues, this rare classification may change. Many experts suspect that some of the amyloidosis diseases are not that rare — just rarely diagnosed. As funding increases for research, our understanding of the amyloid diseases will lead us in new directions.A major challenge is the current lack of early diagnosis for a patient with amyloidosis. This is a key factor. Awareness of all the amyloidosis diseases by the medical community and by the general public is essential in order to turn this around.
HEMOPHILIA
![Picture](/uploads/8/0/7/8/80782094/9766319.jpg?312)
DEFINITION
Hemophilia is a rare disorder in which your blood doesn't clot normally because it lacks sufficient blood-clotting proteins (clotting factors). If you have hemophilia, you may bleed for a longer time after an injury than you would if your blood clotted normally.Small cuts usually aren't much of a problem. The greater health concern is deep bleeding inside your body, especially in your knees, ankles and elbows. That internal bleeding can damage your organs and tissues, and may be life-threatening.Hemophilia is an inherited (genetic) disorder. There's no cure yet. But with proper treatment and self-care, most people with hemophilia can maintain an active, productive lifestyle.
SIGNS AND SYMPTOMS
Signs and symptoms of hemophilia vary, depending on your level of clotting factors. If your clotting-factor level is mildly reduced, you may bleed only after surgery or trauma. If your deficiency is severe, you may experience spontaneous bleeding.
Signs and symptoms of spontaneous bleeding include:
- Unexplained and excessive bleeding from cuts or injuries, or after surgery or dental work
- Many large or deep bruises
- Unusual bleeding after vaccinations
- Pain, swelling or tightness in your joints
- Blood in your urine or stool
- Nosebleeds without a known cause
- In infants, unexplained irritability
- Sudden pain, swelling and warmth in large joints, such as knees, elbows, hips and shoulders, and in your arm and leg muscles
- Bleeding from an injury, especially if you have a severe form of hemophilia
- Painful, prolonged headache
- Repeated vomiting
- Extreme fatigue
- Neck pain
- Double vision
CAUSES AND RISK FACTORS
When you bleed, your body normally pools blood cells together to form a clot to stop the bleeding. The clotting process is encouraged by certain blood particles (platelets and plasma proteins). Hemophilia occurs when you have a deficiency in one of these clotting factors.
Hemophilia is inherited. However, about 30 percent of people with hemophilia have no family history of the disorder. In these people hemophilia is caused by a genetic change (spontaneous mutation).
There are several types of hemophilia. They are classified according to which clotting factor is deficient:
- Hemophilia A, the most common type, is caused by insufficient clotting factor VIII.
- Hemophilia B, the second most common type, is caused by insufficient clotting factor IX.
- Hemophilia C, in which signs and symptoms are often mild, is caused by insufficient clotting factor XI.
Everyone has two sex chromosomes, one from each parent. A female inherits an X chromosome from her mother and an X chromosome from her father. A male inherits an X chromosome from his mother and a Y chromosome from his father.
Hemophilia inheritance depends on your type of hemophilia:
- Hemophilia A or B. The gene that causes them is located on the X chromosome, so it can't be passed from father to son. Hemophilia A or B almost always occurs in boys and is passed from mother to son through one of the mother's genes. Most women with the defective gene are simply carriers and experience no signs or symptoms of hemophilia. Women can experience bleeding symptoms if their factor VIII or IX is moderately decreased.
- Hemophilia C. This disorder can be passed on to children by either parent. Hemophilia C can occur in girls and boys.
DIAGNOSIS
For people with a family history of hemophilia, it's possible to determine during pregnancy if the fetus is affected by hemophilia. However, the testing poses some risks to the fetus. Discuss the benefits and risks of testing with your doctor.
In children and adults, a blood test can show a clotting-factor deficiency. Hemophilia is diagnosed at an average age of 9 months and almost always by age 2. Sometimes, mild hemophilia isn't diagnosed until a person undergoes surgery and experiences excessive bleeding.
TREATMENT
Therapies to stop bleeding depend on the type of hemophilia:
- Mild hemophilia A. Slow injection of the hormone desmopressin (DDAVP) into a vein can stimulate a release of more clotting factor to stop bleeding. Occasionally, DDAVP is given as a nasal medication.
- Moderate to severe hemophilia A or hemophilia B.Bleeding may stop only after an infusion of recombinant clotting factor or clotting factor derived from donated human blood. Repeated infusions may be needed if internal bleeding is severe.
- Hemophilia C. Clotting factor XI, the factor missing in this type of hemophilia, is available only in Europe. In the United States, plasma infusions are needed to stop bleeding episodes.
EXTRA INFORMATION
Christmas disease, also called hemophilia B or factor IX hemophilia, is a rare genetic disorder in which your blood doesn’t clot properly. If you have Christmas disease, your body produces little or no factor IX. This leads to prolonged or spontaneous bleeding. The less factor IX your body produces, the worse your symptoms are. Without treatment, Christmas disease can be fatal.
IMMUNE THROMBOCYTOPENIA
![Picture](/uploads/8/0/7/8/80782094/8021819_orig.jpg)
DEFINITION
Immune thrombocytopenia (THROM-bo-si-toe-PE-ne-ah), or ITP, is a bleeding disorder. In ITP, the blood doesn't clot as it should. This is due to a low number of blood cell fragments called platelets (PLATE-lets) or thrombocytes (THROM-bo-sites).Platelets are made in your bone marrow along with other kinds of blood cells. They stick together (clot) to seal small cuts or breaks on blood vessel walls and stop bleeding.
SIGNS AND SYMPTOMS
Signs include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), especially on the extremities, bleeding from the nostrils and or gums, and menorrhagia (excessive menstrual bleeding), any of which may occur if the platelet count is below 20,000 per μl. A very low count (<10,000 per μl) may result in the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Bleeding time from minor lacerations or abrasions is usually prolonged. Serious and possibly fatal complications due to extremely low counts (<5,000 per μl) include subarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lower gastrointestinal bleeding or other internal bleeding. An ITP patient with an extremely low count is vulnerable to internal bleeding caused by blunt abdominal trauma, as might be experienced in a motor vehicle crash. These complications are not likely when the platelet count is above 20,000 per μl.
DIAGNOSIS
The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (5–10 percent of suspected ITP cases) should be excluded. Such secondary causes include leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. In approximately one percent of cases, autoimmune hemolytic anemia and ITP coexist, a condition referred to as Evans syndrome, a condition that points to CLL as a possible cause. Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.
TREATMENT
With rare exceptions, there is usually no need to treat based on platelet counts. Many older recommendations suggested a certain platelet count threshold (usually somewhere below 20.0/µl) as an indication for hospitalization or treatment. Current guidelines recommend treatment only in cases of significant bleeding. Treatment recommendations sometimes differ for adult and pediatric ITP.[12]
Steroids
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction.[15] Two such products are currently available:
Surgery
CAUSES AND RISK FACTORS
In some people thrombocytopenia is caused by the immune system mistakenly attacking and destroying platelets. If the cause of this immune reaction is unknown, the condition is called idiopathic thrombocytopenic purpura. Idiopathic means "of unknown cause."
In most children with ITP, the disorder follows a viral illness, such as the mumps or the flu. It may be that the infection triggers the immune system malfunction.
Increased breakdown of platelets
Idiopathic thrombocytopenic purpura can occur in anyone at almost any age, but these factors increase the risk:
EXTRA INFORMATION
ITP occurs in about 2 to 5 of every 100,000 children. It is most common in children around the age of 5 or 6, but it can occur at any age. Besides, ITP occurs in about 3 in 100,000 adults every year. It is more common in women than in men between the ares of 30 and 60 years. At other ages, it is just as common in men as it is in women.
DEFINITION
Immune thrombocytopenia (THROM-bo-si-toe-PE-ne-ah), or ITP, is a bleeding disorder. In ITP, the blood doesn't clot as it should. This is due to a low number of blood cell fragments called platelets (PLATE-lets) or thrombocytes (THROM-bo-sites).Platelets are made in your bone marrow along with other kinds of blood cells. They stick together (clot) to seal small cuts or breaks on blood vessel walls and stop bleeding.
SIGNS AND SYMPTOMS
Signs include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), especially on the extremities, bleeding from the nostrils and or gums, and menorrhagia (excessive menstrual bleeding), any of which may occur if the platelet count is below 20,000 per μl. A very low count (<10,000 per μl) may result in the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Bleeding time from minor lacerations or abrasions is usually prolonged. Serious and possibly fatal complications due to extremely low counts (<5,000 per μl) include subarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lower gastrointestinal bleeding or other internal bleeding. An ITP patient with an extremely low count is vulnerable to internal bleeding caused by blunt abdominal trauma, as might be experienced in a motor vehicle crash. These complications are not likely when the platelet count is above 20,000 per μl.
DIAGNOSIS
The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (5–10 percent of suspected ITP cases) should be excluded. Such secondary causes include leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. In approximately one percent of cases, autoimmune hemolytic anemia and ITP coexist, a condition referred to as Evans syndrome, a condition that points to CLL as a possible cause. Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.
TREATMENT
With rare exceptions, there is usually no need to treat based on platelet counts. Many older recommendations suggested a certain platelet count threshold (usually somewhere below 20.0/µl) as an indication for hospitalization or treatment. Current guidelines recommend treatment only in cases of significant bleeding. Treatment recommendations sometimes differ for adult and pediatric ITP.[12]
Steroids
- Initial treatment usually consists of the administration of corticosteroids, a group of medications that suppress the immune system. The dose and mode of administration is determined by platelet count and whether there is active bleeding: in urgent situations, infusions of dexamethasone or methylprednisolone may be used, while oral prednisone or prednisolone may suffice in less severe cases. Once the platelet count has improved, the dose of steroid is gradually reduced while the possibility of relapse is monitored. 60–90 percent will experience a relapse during dose reduction or cessation.[9][13] Long-term steroids are avoided if possible because of potential side-effects that include osteoporosis, diabetes and cataracts.[14]
- Another option, suitable for Rh-positive, non-splenectomized patients is intravenous administration of Rho(D) immune globulin [Human; Anti-D]. The mechanism of action of anti-D is not fully understood. However, following administration, anti-D-coated red blood cell complexes saturate Fcγ receptor sites on macrophages, resulting in preferential destruction of red blood cells (RBCs), therefore sparing antibody-coated platelets. There are two anti-D products indicated for use in patients with ITP: WinRho SDF and Rhophylac. The most common adverse reactions are headache (15%), nausea/vomiting (12%) chills (<2%) and fever (1%).
- There is increasing use of Immunosuppresants such as mycophenolate mofetil and azathioprine because of their effectiveness. In chronic refractory cases, where immune pathogenesis has been confirmed, the off-label use of vincristine, a chemotherapy agent, may be attempted. However, this vinca alkaloid has significant side effects and its use in treating ITP must be approached with caution, especially in children.
- Intravenous immunoglobulin (IVIg) may be infused in some cases. However, while sometimes effective, it is costly and produces improvement that generally lasts less than a month. Nevertheless, in the case of an ITP patient already scheduled for surgery who has a dangerously low platelet count and has experienced a poor response to other treatments, IVIg can increase the count and reduce bleeding risk.
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction.[15] Two such products are currently available:
- Romiplostim (trade name Nplate) is a thrombopoiesis stimulating Fc-peptide fusion protein (peptibody) that is administered by subcutaneous injection. Designated an orphan drug in 2003 under United States law, clinical trials demonstrated romiplostim to be effective in treating chronic ITP, especially in relapsed post-splenectomy patients.[16][17] Romiplostim was approved by the United States Food and Drug Administration (FDA) for long-term treatment of adult chronic ITP on August 22, 2008.[18]
- Eltrombopag (trade name Promacta in the USA, Revolade in the EU) is an orally-administered agent with an effect similar to that of romiplostim. It too has been demonstrated to increase platelet counts and decrease bleeding in a dose-dependent manner.[19] Developed by GlaxoSmithKline and also designated an orphan drug by the FDA, Promacta was approved by the FDA on November 20, 2008.[20]
Surgery
- Splenectomy (removal of the spleen) may be considered, as platelets which have been bound by antibodies are taken up by macrophages in the spleen (which have Fc receptors). The procedure is potentially risky in ITP cases due to the increased possibility of significant bleeding during surgery. Durable remission following splenectomy is achieved in 60 to 65 percent of ITP cases, less so in older subjects.[21] The use of splenectomy to treat ITP has diminished since the development of steroid therapy and other pharmaceutical remedies.
- Platelet transfusion alone is normally not recommended except in an emergency, and is usually unsuccessful in producing a long-term platelet count increase. This is because the underlying autoimmune mechanism that is destroying the patient's platelets will also destroy donor platelets.
CAUSES AND RISK FACTORS
In some people thrombocytopenia is caused by the immune system mistakenly attacking and destroying platelets. If the cause of this immune reaction is unknown, the condition is called idiopathic thrombocytopenic purpura. Idiopathic means "of unknown cause."
In most children with ITP, the disorder follows a viral illness, such as the mumps or the flu. It may be that the infection triggers the immune system malfunction.
Increased breakdown of platelets
- In people with ITP, antibodies produced by the immune system attach themselves to the platelets, marking the platelets for destruction. The spleen, which helps your body fight infection, recognizes the antibodies and removes the platelets from your system. The result of this case of mistaken identity is a lower number of circulating platelets than is normal.
- A normal platelet count is generally between 150,000 and 450,000 platelets per microliter of circulating blood. People with ITP often have platelet counts below 20,000. Because platelets help the blood clot, as their number decreases, your risk of bleeding increases. The greatest risk is when your platelet count falls very low — below 10,000 platelets per microliter. At this point, internal bleeding may occur even without any injury.
Idiopathic thrombocytopenic purpura can occur in anyone at almost any age, but these factors increase the risk:
- Your sex. Women are two to three times more likely to develop ITP than men are.
- Recent viral infection. Many children with ITP develop the disorder after a viral illness, such as mumps, measles or a respiratory infection.
EXTRA INFORMATION
ITP occurs in about 2 to 5 of every 100,000 children. It is most common in children around the age of 5 or 6, but it can occur at any age. Besides, ITP occurs in about 3 in 100,000 adults every year. It is more common in women than in men between the ares of 30 and 60 years. At other ages, it is just as common in men as it is in women.