A patient with TTP (thrombotic thrombocytopenic purpura) has microangiopathic hemolytic anemia and thrombocytopenia due to platelet-rich thrombi in microvessels. The fundamental pathogenesis involves:

• A Autoantibodies against GPIIb/IIIa preventing platelet aggregation
• B Complement-mediated platelet lysis with terminal complement activation
• C Factor V Leiden mutation causing hypercoagulability in small vessels
• D Deficiency or inhibition of ADAMTS13 metalloprotease causing accumulation of ultra-large vWF multimers ✓

Explanation

TTP is caused by deficiency of ADAMTS13 (a disintegrin and metalloprotease), either hereditary or due to inhibitory autoantibodies. ADAMTS13 normally cleaves ultra-large vWF (ULvWF) multimers released from endothelium. Without cleavage, ULvWF accumulates and anchors platelets, forming platelet-rich microvascular thrombi causing MAHA and thrombocytopenia. Anti-GPIIb/IIIa antibodies cause ITP. Complement activation is aHUS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.