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INTRODUCTION

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ESSENTIALS OF DIAGNOSIS

  • Thrombotic microangiopathy is caused by thrombosis within the microvasculature of various organs.

  • Patients typically present with thrombocytopenia, hemolytic anemia, and dysfunction of affected organs (most commonly the kidneys and brain).

  • ADAMTS13 activity and the presence of Shiga-like toxin in stool should be evaluated in all patients with suspected TMA. Specific tests for other causes of TMA are based upon the clinical scenario.

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GENERAL CONSIDERATIONS

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The thrombotic microangiopathies (TMAs) are a group of diseases caused by thrombosis in the microvasculature of tissue beds throughout the body. Patients present with microangiopathic hemolytic anemia, thrombocytopenia, and injury of affected organs. TMA can develop in patients exposed to a wide range of different diseases or stressors, including infections, cancers, drugs, autoimmune diseases, and pregnancy. There are also two primary forms of TMA: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS).

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HUS and TTP are caused by distinct pathologic processes that cause similar clinical presentations. The treatment of these diseases is different, so the proper diagnosis is important. For the secondary causes of TMA, the approach is to treat or remove the triggering event. Episodes of HUS and TTP can be triggered by illness, medications, or pregnancy, however, so in practice the distinction of the primary and secondary forms of TMA can be difficult.

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THROMBOTIC THROMBOCYTOPENIC PURPURA

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ESSENTIALS OF DIAGNOSIS

  • TTP has traditionally been described as presenting with thrombocytopenia, hemolytic anemia, neurologic symptoms, renal insufficiency, and fever. However, patients do not usually present with all five of these findings.

  • Low activity (<10% activity) of ADAMTS13 [a protease that cleaves von Willebrand factor (vWF)] is considered diagnostic of TTP.

  • Plasma exchange is the treatment of choice for patients with TTP, and immunosuppression with corticosteroids and rituximab may be beneficial in some patients.

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GENERAL CONSIDERATIONS

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TTP is associated with decreased function of the zinc metalloprotease ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin-1-domains, type 13). The incidence of TTP is estimated to be less than 2 cases per million people and it is more common in women than in men. TTP typically presents in patients between 20 and 50 years old, although patients with congenital deficiency of ADAMTS13 usually present in childhood.

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PATHOGENESIS

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Endothelial cells produce large multimers of vWF that are normally cleaved by ADAMTS13. Decreased ADAMTS13 activity permits the persistence of unusually large vWF multimers that can bind to extracellular matrix and platelets, inducing platelet aggregation, thrombocytopenia, thrombosis, and ischemia of affected organs. Some patients have congenital deficiency of ADAMTS13, a condition termed Upshaw–Shulman syndrome. In most adult patients with TTP, however, ADAMTS13 activity is reduced due to an inhibitory autoantibody to the protein.

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CLINICAL FINDINGS

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A. Symptoms and Signs

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TTP is traditionally described as manifesting with microangiopathic hemolytic anemia, thrombocytopenia, fever, neurologic symptoms, and renal failure, but only a small percentage of patients have all five of ...

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