Thrombotic Thrombocytopenic Purpura and Hemolytic-Uremic Syndrome
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Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are thrombotic microangiopathies (TMAs) caused by platelet–vWF aggregates and platelet–fibrin aggregates, respectively, resulting in thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and organ ischemia. Usually, clinical and laboratory features permit differentiation of TTP from HUS. TMA may occur in association with DIC, HIV infection, malignant hypertension, vasculitis, organ and stem cell transplant–related toxicity, adverse drug reactions, and pregnancy-related complications of pre-eclampsia/eclampsia and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome.
Sporadic TTP has an incidence of approximately 11.3 cases per 10 persons, occurring more frequently in women and African Americans.1 Typical HUS usually occurs in gastroenteritis outbreaks affecting children. Adults may present with both typical and atypical (non–gastroenteritis-associated) variants of HUS.
- Autoantibody-mediated removal of plasma vWF-cleaving protease: A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), leading to elevated levels of abnormally large vWF multimers, typically causes sporadic TTP.2 The abnormal vWF multimers spontaneously adhere to platelets and may produce occlusive vWF–platelet aggregates in the microcirculation and subsequent microangiopathy. Second-hit events may involve endothelial dysfunction or injury.
- Severe ADAMTS13 deficiency does not cause HUS and other types of TMA, with the exception of some cases associated with HIV and pregnancy.
- Typical or enteropathic HUS has an association with Escherichia coli (O157:H7) production of Shiga-like toxins in Shiga toxigenic E. coli HUS (STEC-HUS).
- HUS can also be associated with transplantation, endothelial-damaging drugs, and pregnancy.3
- Inherited or acquired defects in regulation of the alternative complement pathway are present in 30%–50% of atypical HUS cases.4