A 25-year-old woman develops thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological symptoms, and fever 5 days after starting clopidogrel. Peripheral smear shows schistocytes. ADAMTS13 activity is severely reduced (<10%). The pathomechanism involves:

• A Complement-mediated destruction of platelets on prosthetic valves
• B Complement factor H mutation causing uncontrolled alternative pathway activation
• C Heparin-induced platelet factor 4/heparin antibodies causing platelet activation
• D Anti-ADAMTS13 IgG inhibitory autoantibodies causing failure to cleave ultra-large vWF multimers ✓

Explanation

Thrombotic thrombocytopenic purpura (TTP) is caused by severe ADAMTS13 deficiency — usually due to autoimmune IgG inhibitory antibodies against ADAMTS13 (the vWF-cleaving protease). Absent ADAMTS13 activity allows accumulation of ultra-large vWF multimers (ULvWF) on endothelium, which bind platelets forming widespread platelet-rich microthrombi in arterioles and capillaries, causing MAHA (schistocytes) and thrombocytopenia. Classic pentad: MAHA + thrombocytopenia + neurological symptoms + fever + renal impairment (but full pentad is uncommon). Treatment: therapeutic plasma exchange (removes antibodies and replenishes ADAMTS13) + corticosteroids + rituximab for refractory cases.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.