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.
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.
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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.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 274150; Last Update: 3/12/1994.
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