TTP is associated with the deposition of platelet-rich hyaline thrombi within the microcirculation of the brain, kidneys, heart, pancreas, spleen, adrenal glands, and other organ systems. In a majority of patients with TTP, the formation of these thrombi has been attributed to the abnormal accumulation of unusually large (UL) von Willebrand factor (vWF) multimers. vWF is synthesized in endothelial cells and assembled into multimers ranging in size from small dimers to huge unusually large multimers (ULvWF). When released into the plasma, ULvWF multimers are quickly reduced in size by a vWF-specific protease called ADAMTS-13 (a disintegrinlike and metalloprotease with thrombospondin type 1 repeats). Very low or absent ADAMTS13 activity is associated with accumulation of ULvWF multimers, which can then attach to platelets and promote platelet activation and aggregation, leading to the formation of platelet thrombi. Patients with the familial form of TTP have severe deficiencies of ADAMTS13 activity and mutated ADAMTS13 genes located on chromosome 9q34.
Most patients with sporadic/idiopathic TTP have very low or undetectable ADAMTS13 activity at presentation. Inhibitory antibodies against ADAMTS-13 are detected in some, but not all, patients, which may be due to the insensitivity of current assay methods. As is seen in other autoimmune diseases, there is an increased incidence of sporadic/idiopathic TTP, ADAMTS-13 deficiency, and autoantibodies in African- American women. In patients diagnosed clinically with HUS, however, ADAMTS13 activity is usually normal or only moderately decreased, and autoantibodies are not detected.
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