Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia (Coombs-negative hemolysis with prominent red cell fragmentation). Ischemic necrosis of brain, kidneys, heart, pancreas, and other tissues can result from disseminated arteriolar occlusions by platelet-von Willebrand factor (vWF) microthrombi. In many patients, there is evidence for autoantibodies that inhibit or clear the enzyme, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin-
1-like domains), which is responsible for cleaving ultralarge vWF multimers released from endothelium. Thus, the pathogenesis of idiopathic (primary) TTP likely reflects the formation of arteriolar-occluding complexes of ultralarge vWF multimers and platelets, thereby explaining both the thrombocytopenia and the tissue ischemia. "Secondary" TTP has been reported to occur in association with pregnancy, certain drugs (e.g., ticlopidine, clopidogrel, quinine, cyclosporine, mitomycin), autoimmune disorders (systemic lupus erythematosus), organ transplantation, and infections (human immunodeficiency virus, bacterial endocarditis). TTP clinically resembles a nephrotropic microangiopathic hemolytic anemia known as hemolytic uremic syndrome (HUS); however, there are certain unique triggers of HUS (especially, preceding infection with E. coli H0157) and anti-ADAMTS13 autoantibodies are not detected in HUS.
In recent years, an entity known as postoperative TTP has been recognized (Naqvi et al., 2004). The most common clinical setting is post-cardiac surgery, with cases seen beginning 2-19 days (median, day 5-6) after surgery (Chang et al., 1996; Pavlovsky and Weinstein, 1997; Chang and Ikhlaque, 2004; Almehmi et al., 2004). Other preceding events have included vascular surgery (Chang et al., 1996), abdominal surgery (Robson and Abbs, 1997; Chang et al., 2000), and orthopedic surgery (Iosifidis et al., 2006). The authors advocate plasmapheresis (the therapeutic mainstay of primary TTP) when postoperative TTP is diagnosed. Given the frequent formation of anti-PF4/heparin antibodies after surgery in heparin-treated patients, it is possible that coincidental formation of nonpathogenic anti-PF4/ heparin antibodies could cause a false diagnosis of HIT in a patient with this rare entity of postoperative TTP. On the other hand, peripheral digit ischemic syndrome leading to amputations has been reported in post-cardiac surgery TTP (Chang and Ikhlaque, 2004), further blurring the distinctions between HIT and TTP. One patient has been reported in whom the authors believed the patient had concomitant TTP and HIT (Benke and Moltzan, 2005); an alternative explanation is that HIT-associated DIC produced thrombi in the renal microvasculature (thus, HIT may have mimicked TTP).
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