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Thrombotic thrombocytopenia purpura (TTP) is a rare, serious blood disease. Major symptoms may include a severe decrease in the number of blood platelets (thrombocytopenia), abnormal destruction of red blood cells (hemolytic anemia), and disturbances in the nervous system. Kidney dysfunction and fever are also common. The exact cause of thrombotic thrombocytopenic purpura is unknown.
In addition to thrombocytopenia and hemolytic anemia, blood platelets may clot in the blood vessels of many organs, potentially blocking the normal flow of blood through the vessels. Disturbances affecting the nervous system may include headaches, mental changes, confusion, speech abnormalities, slight or partial paralysis (paresis), seizures, or coma.
Fever, blood plasma proteins in the urine (proteinuria), and a very small number of red blood cells in the urine (hematuria) may also occur. Affected individuals also exhibit red rash-like areas of skin or patches of purplish discoloration (purpura) resulting from abnormal bleeding into the mucous membranes (the thin, moist layer lining the body's cavities) and into the skin. Additional features of TTP include abnormally heavy bleeding (hemorrhaging), weakness, fatigue, lack of color (pallor), and abdominal pain with nausea and vomiting. In half of individuals with TTP, increased levels of a chemical compound known as creatinine is found in the blood serum.
Acute renal failure occurs in only about 10 percent of individuals with TTP. Urine flow is often lower than normal. Within days, swelling of the feet, shortness of breath, headache, and fever may occur. Retention of water and salt in the blood may lead to high blood pressure, changes in brain metabolism, and congestion in the heart and lungs. Acute renal failure may lead to a buildup (accumulation) of potassium in the blood (hyperkalemia), which may cause irregular heartbeat.
Abnormalities in the retina (the light-sensitive layer of the eye) have been found in females with TTP after taking oral contraceptives. Clearness (acuity) of vision is usually not affected.
There may be possible serious complications during pregnancy in females with TTP. In general, TTP often occurs suddenly with great severity and may recur or persist.
The exact cause of TTP is not known. However, the disease is associated with a deficiency of an enzyme involved in blood clotting called the von Willebrand factor cleaving protease (also called ADAMTS13). The deficiency of this enzyme allows large complexes of the clotting protein known as von Willebrand factor to circulate in the blood, resulting in platelet clotting and the destruction of red blood cells.
It is believed that there is an acquired (noninherited) form of TTP and a familial form. The acquired form may appear later in life, in late childhood or adulthood, and affected individuals may have a single episode or recurring episodes.
If the disorder is present at birth (familial form), signs and symptoms may typically appear earlier, in infancy or early childhood.
The acquired form may involve an autoimmune reaction. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons.
TTP may also be influenced by hormones. In some cases of TTP, relapses coincide with the use of oral contraceptives and with menstrual cycles (cyclic TTP). Some cases have been associated with the use of estrogen.
Some cases of TTP have been associated with the use of antiplatelet drugs (also known as platelet inhibitors) such as clopidogrel or ticlopidine. More research is needed to determine the exact relationship between these drugs and TTP.
TTP can occur as a consequence of AIDS, the AIDS-related complex, or the human immunodeficiency virus (HIV) infection.
The current rate of occurance for TTP is about 3.7 cases per million people each year. One estimate places the overall incidence rate at four of 100,000 individuals. Two-thirds of individuals with TTP are women. It usually affects people between 20 to 50 years old.
TTP is occasionally associated with pregnancy and collagen-vascular diseases (a group of diseases affecting connective tissue).
TTP appears to occur more frequently than usual in intravenous drug addicts and homosexual men who have human immunodeficiency virus (HIV) infection.
Childhood-onset thrombotic thrombocytopenic purpura (TTP) often occurs concurrently with systemic lupus erythematosus (SLE). A search of the literature by investigators at the University of Toronto demonstrated that approximately half of the cases of childhood-onset TTP met criteria for "incipient or definite SLE". The best indicator for the presence or later development of SLE appeared to be high-grade proteinuria (excessive serum proteins in the urine) at the time of diagnosis of TTP. The researchers recommended that physicians rule out concomitant SLE in all children who present with TTP.
Symptoms of the following disorders can be similar to those of thrombotic thrombocytopenia purpura (TTP). Comparisons may be useful for a differential diagnosis:
Hemolytic-uremic syndrome (HUS) is a rare disorder that primarily affects young children between the ages of one and 10 years, particularly those under the age of four years. In many cases, the onset of HUS is preceded by a flu-like illness (gastroenteritis) characterized by vomiting, abdominal pain, fever, and diarrhea, which, in some cases, may be bloody. Symptoms of HUS usually become apparent three to 10 days after the development of gastroenteritis and may include sudden paleness (pallor), irritability, weakness, lack of energy (lethargy), and/or excretion of abnormally diminished amounts of urine (oliguria). The disease typically progresses to include inability of the kidneys to process waste products from the blood and excrete them into the urine (acute renal failure); a decrease in circulating red blood cells (microangiopathic hemolytic anemia); a decrease in circulating blood platelets, which assist in blood clotting functions (thrombocytopenia); and the abnormal accumulation of platelets within certain blood vessels (microthrombi), reducing the blood flow to several organs (e.g., kidneys, pancreas, brain) potentially leading to multiple organ dysfunction or failure. In some cases, neurological problems may be present at the onset of HUS or may occur at any time during the disorder's progression. Neurological symptoms may include dizziness, seizures (partial or generalized), disorientation or confusion, and/or loss of consciousness (coma). (For more information on this disorder, choose "Hemolytic-Uremic" as your search term in the Rare Disease Database.)
Thrombotic microangiopathy is the occurrence of TTP and HUS together. It is also called the TTP-HUS complex. It has been suggested that TTP and HUS are actually variants of the same disease.
Idiopathic thrombocytopenic purpura (ITP) is a blood disease with no specific known cause (idiopathic). It is characterized by thrombocytopenia, abnormal bleeding into the skin and mucous membranes, and anemia. ITP occurs most frequently in children and young adults, and more frequently in females than males. A viral infection may precede ITP. (For more information on this disorder, choose "ITP" as your search term in the Rare Disease Database.)
Henoch-Shonlein purpura is one of a group of disorders characterized by purplish or brownish-red discolorations of the skin caused by abnormal bleeding into the skin and mucous membranes. This blood disorder may affect the skin, joints, gastrointestinal system, kidneys, and in a few cases the central nervous system. Major symptoms may include a rash, fever, weakness, pain in the joints or abdomen, vomiting, blood in the stool, and anemia. Central nervous system symptoms may include headaches, perceptual changes, and seizures. The exact cause of Henoch-Shonlein purpura is unknown, but it may be related to an extreme allergic response to foods, drugs, or insect bites. (For more information on this disorder, choose "Henoch-Shonlein" as your search term in the Rare Disease Database.)
Thrombocytopenia is a general term referring to a group of blood disorders including TTP, HUS, and ITP. It is characterized by a severe decrease in the number of blood platelets and excessive bleeding into the skin or mucous membranes. Anemia may occur producing weakness, fatigue, and signs of congestive heart failure. (For more information on this disorder, choose "Thrombocytopenia" as your search term in the Rare Disease Database.)
Rapid diagnosis and immediate treatment is very important in TTP. A diagnosis may be made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings.
In many cases, plasmapheresis, or plasma exchange, is used to remove the large complexes of von Willebrand protein from the blood. In this process, blood is drawn from the affected individual, blood cells are separated from plasma, the patient's plasma is replaced with healthy plasma, and the blood is then returned to the patient as a blood transfusion.
The blood product SD plasma (VIPLAS/SD) has been approved by the Food and Drug Administration (FDA) for the treatment of TTP. SD plasma was developed by the company former known as V.I. Technologies, Inc., and now known as Panacos Pharmaceuticals.
Genetic counseling may be of benefit for affected individuals and their families when TTP has affected other family members. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
When the standard treatment approach (in this case, plasma exchange) is not effective (refractory cases), treatment may involve the drug vincristine, an immunosuppressant; corticosteroids; or antiplatelet drugs.
Another treatment approach that has been effective in some cases is the use of intravenous immunoglobulins (IVIG), in which a solution of concentrated antibodies is delivered directly into a vein. Additional study is needed of this alternative approach to treatment for individuals with TTP.
For cases when other treatments have been tried and not been effective, removing the spleen (splenectomy) may be considered. The safety and effectiveness of this treatment approach for individuals with TTP continues to be evaluated.
Algazy, KM. Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome of Adults in The NORD Guide to Rare Disorders, Lippincott, Williams & Wilkins. 2003:416.
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Bennett CL, et al. Thrombotic thrombocytopenia purpura associated with clopidogrel. N Engl J Med. 2000;342:1773-77.
Pogliani EM, et al. Defibrotide in recurrent thrombotic thrombocytopenia purpura. Clin Appl Thromb Hemost. 2000;6:69-70.
Rock G, et al. Thrombotic thrombocytopenia purpura treatment in year 2000. Haematolgica. 2000;85:410-19.
Chemnitz HM, et al. Thrombotic thrombocytopenia purpura (Moschkowitz syndrome) caused by ticlopidine. Med Klin. 2000;95:96-100.
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FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 274150; Last Update: 3/12/1994.
Report last updated: 2007/07/23 00:00:00 GMT+0