A 28-year-old woman presents with thrombocytopenia, haemolytic anaemia (schistocytes on smear), fever, neurological symptoms, and renal failure. ADAMTS13 activity is <10%. This finding indicates that thrombotic thrombocytopenic purpura (TTP) in this patient is driven by:

• A Congenital absence of ADAMTS13 due to ADAMTS13 gene mutation (Upshaw-Schulman syndrome)
• B Autoantibody-mediated inhibition of ADAMTS13 (acquired TTP), leading to accumulation of ultra-large vWF multimers that cause platelet-rich microthrombi ✓
• C Shiga toxin-mediated ADAMTS13 cleavage causing vWF multimer fragmentation
• D Complement-mediated platelet lysis due to CD55/CD59 deficiency

Explanation

In acquired TTP, IgG autoantibodies (usually IgG4) against ADAMTS13 inhibit or clear the protease, reducing activity to <10% of normal. ADAMTS13 normally cleaves ultra-large von Willebrand factor (ULvWF) multimers secreted from Weibel-Palade bodies of endothelial cells into smaller haemostatically appropriate multimers. Without ADAMTS13, ULvWF multimers persist on the endothelial surface and in plasma, spontaneously binding and activating platelets under high-shear conditions to form platelet-rich microthrombi in the microcirculation — causing the pentad of TTP. This clinical presentation in a young woman likely represents immune-mediated TTP. Upshaw-Schulman syndrome (congenital TTP) presents in neonates/childhood. Shiga toxin-HUS primarily injures renal endothelium directly, not via ADAMTS13. CD55/CD59 deficiency is PNH.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.