A patient with TTP has ADAMTS13 activity <10% due to an autoantibody against ADAMTS13. ADAMTS13 normally cleaves von Willebrand factor at which specific site, and what is the consequence of its deficiency?

• A Cleaves VWF at its N-terminal propeptide, preventing secretion of ultra-large multimers from Weibel-Palade bodies
• B Cleaves VWF at the GpIb binding site on A1 domain, preventing platelet adhesion under high shear
• C Cleaves VWF into monomers by disulfide bond reduction in the C-terminal domain
• D Cleaves VWF at Tyr1605-Met1606 bond within the A2 domain; deficiency causes persistence of ultra-large VWF multimers that spontaneously bind platelets ✓

Explanation

ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) cleaves VWF at the Tyr1605-Met1606 peptide bond within the VWF A2 domain under high shear stress conditions. This cleavage is essential for breaking down ultra-large VWF (UL-VWF) multimers secreted from endothelial Weibel-Palade bodies. In TTP, deficient ADAMTS13 allows UL-VWF multimers to persist in circulation; these have multiple GPIbα binding sites and spontaneously agglutinate platelets under shear, causing microthrombi, microangiopathic hemolytic anemia, and thrombocytopenia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.