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Thrombotic thrombocytopenic purpura

What is thrombotic thrombocytopenic purpura?

Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Resulting complications include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.

In people with thrombotic thrombocytopenic purpura, clots in blood vessels are formed from clumps of platelets. Platelets are cell fragments that play a critical role in blood clotting. Because a large number of platelets are used to form clots in people with this disorder, fewer platelets are available to circulate in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to bleeding just under the surface of the skin, resulting in purplish spots called purpura.

This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.

The two major forms of thrombotic thrombocytopenic purpura are an acquired (noninherited) form and a familial form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or complications of the disorder may recur over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood. In people with the familial form, signs and symptoms often recur on a regular basis.

How common is thrombotic thrombocytopenic purpura?

The precise incidence of this condition is unknown, but researchers estimate that it affects 4 to 7 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thrombotic thrombocytopenic purpura is much more common than the familial form.

What genes are related to thrombotic thrombocytopenic purpura?

Mutations in the ADAMTS13 gene cause thrombotic thrombocytopenic purpura.

The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Both the familial form and the acquired form of thrombotic thrombocytopenic purpura result from a severe reduction in the activity of this enzyme. The familial form is caused by mutations in the ADAMTS13 gene that disrupt the enzyme's function. People with the acquired form do not have mutations in this gene; instead, their immune systems often produce specific proteins called antibodies that block the activity of the ADAMTS13 enzyme.

A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels unpredictably, causing organ damage and the other features of thrombotic thrombocytopenic purpura.

Researchers believe that other genetic or environmental factors may contribute to the signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications.

How do people inherit thrombotic thrombocytopenic purpura?

The familial form of thrombotic thrombocytopenic purpura is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. The acquired form of thrombotic thrombocytopenic purpura is not inherited.

Thrombotic Thrombocytopenic Purpura on Wikipedia

'''Thrombotic thrombocytopenic purpura''' ('''TTP''' or ''Moschcowitz disease'') is a rare disease disorder of the coagulation system that in most cases arises from the deficiency or inhibition of the enzyme responsible for cleaving von Willebrand factor. It is a serious condition that leads to hemolysis and end-organ damage, and may require plasmapheresis therapy.

Signs and symptoms

Classically, the following five symptoms are indicative of this elusive disease: * Fluctuating neurology symptoms, such as bizarre behavior, altered mental status, stroke or headaches (65%) * Acute renal failure (46%) * Fever (33%) * Thrombocytopenia (low platelet count), leading to bruising or frank purpura; * Microangiopathic haemolytic anaemia (anemia and a characteristic blood film)

Diagnosis

The combination of the symptoms and a routine blood film often lead to the detection of ''schistocytes'' (fragmented red cells) and "helmet cells" on the blood film. This is indicative of breakdown of red blood cells through factors in the small blood vessels. Other tests to be performed are reticulocyte counts, lactate dehydrogenase, direct antiglobulin test (DAT/Coombs' test), renal function (creatinine), electrolytes and liver enzymes. Very high LDH levels may be present; these mainly originate from the poorly perfused tissues, and not so much from the hemolysis. The above symptoms and findings are the main criteria for diagnosis, although the fever, renal and neurological symptoms can be absent. Increased lactate dehydrogenase levels and a negative direct antiglobulin test (DAT, Coombs' test) in the context of microangiopathic haemolytic anaemia (MAHA) are indicative of TTP. The main differential diagnosis is between TTP and hemolytic uremic syndrome (HUS). The syndromes show a remarkable overlap in symptoms, ... [ Read More ]

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