Pathophysiology and Treatment of Thrombotic Microangiopathy

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Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and tissue damage caused by microvascular thrombosis. Clinical manifestations of thrombotic microangiopathy vary considerably, depending in part on predisposing conditions such as infections, cancer, organ transplantation, malignant hypertension, toxemia of pregnancy, and a variety of drugs. When thrombotic microangiopathy occurs in adults without a secondary cause, in most cases renal damage is a minor feature and neurological symptoms are prominent; this syndrome is called idiopathic thrombotic thrombocytopenic purpura (idiopathic TTP) and usually is due to acquired, autoimmune deficiency of ADAMTS13, a metalloprotease that cleaves von Willetjrand factor (VWF) and inhibits the growth of platelet thrombi. In some clinically similar cases, ADAMTS13 levels are normal and the cause of TTP almost always is unknown. Patients with severe ADAMTS13 deficiency usually respond to plasma exchange and the mortality for this subgroup is v15%, although a high titer of inhibitory autoantibody correlates with high likelihood of relapsing disease. In contrast, patients with detectable ADAMTS13 activity almost never relapse, and whether plasma exchange improves their survival is uncertain. Several studies suggest that ADAMTS13 activity and inhibitor assays provide useful prognostic information, but current tests have significant shortcomings in terms of speed and sensitivity, especially for inhibitor detection.