Thrombotic thrombocytopenic purpura (TTP) is distinguished from hemolytic uremic syndrome (HUS) clinically and mechanistically. The pathogenesis of idiopathic (acquired) TTP involves:
- A Shiga toxin from E. coli O157:H7 directly damaging endothelium
- B Autoantibodies against ADAMTS13 (VWF-cleaving protease), causing accumulation of ultra-large von Willebrand factor multimers and platelet-rich thrombi ✓
- C Complement factor H or factor I deficiency activating alternative complement pathway
- D Heparin-induced IgG antibodies activating platelets via FcγRIIA
Explanation
Acquired (immune-mediated) TTP is caused by autoantibodies (usually IgG) against ADAMTS13, the metalloprotease that cleaves ultra-large VWF (UL-VWF) multimers secreted by endothelial cells. Without ADAMTS13 activity, UL-VWF accumulates on endothelial surfaces and in plasma, where it causes platelet agglutination under high shear stress, forming hyaline platelet microthrombi in the microcirculation, causing MAHA (microangiopathic hemolytic anemia) and thrombocytopenia. Shiga toxin causes typical HUS (atypical HUS involves complement dysregulation with factor H/I/CFB mutations); HIT involves heparin-PF4 antibody complexes.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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