Skip to Main Content

Idiopathic thrombotic thrombocytopenic purpura (TTP) is associated with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis that results in variable injury of the central nervous system, kidney, and other organs. Most cases of TTP are caused by autoantibodies to ADAMTS13, a metalloprotease that cleaves von Willebrand factor (VWF) and inhibits VWF-dependent platelet aggregation. TTP is usually fatal if untreated. Most patients respond to plasma exchange, although many have relapsing disease. Clinically similar thrombotic microangiopathy can occur with normal ADAMTS13 levels. Secondary thrombotic microangiopathy occurs in association with metastatic cancer, infections, organ transplantation, and certain drugs. Secondary thrombotic microangiopathy has a lower likelihood of responding to plasma exchange and a lower survival rate.

Heparin-induced thrombocytopenia (HIT) is a significant complication of treatment with heparin, especially unfractionated high-molecular-weight heparin. It is associated with mild to moderate thrombocytopenia, although the main concern is the high frequency of both arterial and venous thrombotic complications. HIT is an immune complex-based disorder involving heparin/platelet factor 4 (PF4) complexes. Immediate cessation of heparin is required, but the risk of subsequent thrombosis remains high. Direct thrombin inhibitors are the present-day treatment of choice to limit thrombotic complications.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: ADAMTS, a disintegrin and metalloprotease with thrombospondin type 1 repeats; APS, antiphospholipid syndrome; aPTT, activated partial thromboplastin time; DDAVP, desmopressin, 1-deamino-8-d-arginine-vasopressin; D+HUS, diarrhea-associated hemolytic uremic syndrome; DHUS, diarrhea-negative hemolytic uremic syndrome; GP, glycoprotein; HELLP, hemolysis, elevated liver enzymes, and low platelet count; HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; Ig, immunoglobulin; LDH, lactate dehydrogenase; MCP, membrane cofactor protein; MTHFR, methylenetetrahydrofolate reductase; PF4, platelet factor 4; PT, prothrombin time; SLE, systemic lupus erythematosus; TTP, thrombotic thrombocytopenic purpura; VWF, von Willebrand factor.

Definition and History

Thrombotic microangiopathy refers to a combination of microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis, regardless of cause or specific tissue involvement. Various kinds of thrombotic microangiopathy differ in pathogenesis and prognosis, but can be difficult to distinguish because their clinical features overlap.

Thrombotic thrombocytopenic purpura (TTP) is a form of thrombotic microangiopathy in which tissue injury can affect any organ but often results in neurologic damage and fever. Renal involvement is common but oliguric renal failure is not. TTP usually is associated with acquired autoantibodies that inhibit a disintegrin and metalloprotease thrombospondin type 1 repeats (ADAMTS)13.

Congenital TTP, or Upshaw-Schulman syndrome, refers to TTP that is caused by inherited deficiency of ADAMTS13.

Hemolytic uremic syndrome (HUS) refers to thrombotic microangiopathy that mainly affects the kidney and usually causes oliguric or anuric renal failure. Diarrhea-associated or typical HUS (D+HUS) is caused by enteric infection with Shiga toxin-producing Gram-negative bacilli, and usually is associated with a prodrome of diarrhea. Diarrhea-negative or atypical HUS (DHUS) is not associated with diarrhea or Shiga toxin-producing organisms and occurs ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.