Pathophysiology
Clinical meaning
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) caused by severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13. ADAMTS13 normally cleaves ultra-large von Willebrand factor (UL-vWF) multimers released from endothelial cells into smaller, less thrombogenic fragments. When ADAMTS13 activity falls below 10% (acquired TTP: autoimmune IgG antibodies against ADAMTS13; congenital TTP/Upshaw-Schulman syndrome: inherited ADAMTS13 gene mutations), UL-vWF multimers accumulate on the endothelial surface and in the circulation, spontaneously capturing platelets and forming microthrombi in the arteriolar and capillary microcirculation. These platelet-rich microthrombi cause two hallmark consequences: (1) consumptive thrombocytopenia (profound platelet consumption producing severe thrombocytopenia, typically <30,000/mcL), and (2) microangiopathic hemolytic anemia (MAHA) as red blood cells are mechanically sheared passing through partially occluded microvessels, producing schistocytes (fragmented RBCs) on peripheral blood smear. Organ ischemia results from microvascular thrombosis, predominantly affecting the brain (neurological symptoms: confusion, headache, seizures, focal deficits, coma) and kidneys (mild renal impairment — creatinine usually only mildly elevated, distinguishing TTP from HUS where renal failure predominates). The classic pentad (thrombocytopenia, MAHA, neurological symptoms, renal dysfunction, fever) is present in fewer than 5% of...