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Key Features

Essentials of Diagnosis

  • Microangiopathic hemolytic anemia and thrombocytopenia, in the absence of another plausible explanation, are sufficient for the diagnosis

  • Fever, neurologic abnormalities, and kidney disease may occur concurrently but are not required for diagnosis

  • Kidney dysfunction is more common and more severe in hemolytic-uremic syndrome (HUS)

General Considerations

  • The thrombotic microangiopathies (TMAs) include but are not limited to

    • Thrombotic thrombocytopenic purpura (TTP)

    • HUS

  • These disorders are characterized by

    • Thrombocytopenia, due to the incorporation of platelets into thrombi in the microvasculature

    • Microangiopathic hemolytic anemia, which results from shearing of erythrocytes in fibrin networks in the microcirculation

    • Mutations in complement genes (such as factor H, a complement regulator) account for the uncontrolled activation of complement

  • In idiopathic TTP, autoantibodies against the ADAMTS-13 (A disintegrin and metalloproteinase with thrombospondin type 1 repeat, member 13), also known as the von Willebrand factor cleaving protease, leads to accumulation of ultra-large von Willebrand factor (vWF) multimers

    • These multimers bridge and aggregate platelets in the absence of hemostatic triggers

    • This bridging and aggregation in turn leads to the vessel obstruction and various organ dysfunctions seen in TTP

  • In some cases of pregnancy-associated TMA, an antibody to ADAMTS-13 is present

  • In contrast, the activity of the ADAMTS-13 in congenital TTP is decreased due to a mutation in the gene encoding for the molecule

  • Damage to endothelial cells may also lead to TMA

  • Certain drugs have been associated with the development of TMA

    • Cyclosporine

    • Quinine

    • Ticlopidine

    • Clopidogrel

    • Mitomycin C

    • Bleomycin

Clinical Findings

Symptoms and Signs

  • Microangiopathic hemolytic anemia and thrombocytopenia are presenting signs in all patients with TTP and most patients with HUS

  • In a subset of patients with HUS, the platelet count remains in the normal range

  • Only approximately 25% of patients with TMA manifest all components of the original pentad of findings (Table 14–4)

    • Microangiopathic hemolytic anemia

    • Thrombocytopenia

    • Fever

    • Kidney disease

    • Neurologic system abnormalities

  • Most patients (especially children) with HUS have a recent or current diarrheal illness, often bloody

  • Neurologic manifestations may result from deposition of microthrombi in the cerebral vasculature

    • Headache

    • Somnolence

    • Delirium

    • Seizures

    • Paresis

    • Coma

Table 14–4.Presentation and management of thrombotic microangiopathies.

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