A 35-year-old woman presents with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological symptoms, fever, and renal impairment (pentad). ADAMTS13 activity is <5% and ADAMTS13 inhibitor is positive. What is the pathomechanism of this condition?

• A Shiga toxin-mediated endothelial injury activating ADAMTS13
• B Complement-mediated endothelial injury through alternative pathway dysregulation
• C Heparin-induced thrombocytopenia with paradoxical arterial thrombosis
• D Autoantibody-mediated inhibition/depletion of ADAMTS13, causing accumulation of ultra-large vWF multimers that cause platelet microthrombi ✓

Explanation

This is acquired TTP (thrombotic thrombocytopenic purpura). ADAMTS13 is the metalloprotease that cleaves unusually large von Willebrand factor (UL-vWF) multimers released from endothelial cells. In acquired TTP, IgG autoantibodies neutralize or deplete ADAMTS13 (activity <10% diagnostic). Uncleaved UL-vWF multimers accumulate in the circulation, spontaneously platelet-binding under shear stress → widespread platelet microthrombosis in microvessels → MAHA (mechanical RBC fragmentation), thrombocytopenia, and ischemic organ injury. Congenital ADAMTS13 deficiency causes Upshaw-Schulman syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.