A 44-year-old woman presents with fever, confusion, petechiae over the trunk, Hb 6.9 g/dL, platelets 15,000/µL, creatinine 1.1 mg/dL, and LDH markedly elevated. Schistocytes are abundant on smear and the direct antiglobulin test is negative. The underlying defect involves:

• A Antibodies against glomerular basement membrane
• B Deficiency of a von Willebrand factor cleaving metalloprotease ✓
• C Shiga toxin mediated endothelial injury after bacterial gastroenteritis
• D Inherited deficiency of ADAMTS2 pro-collagen peptidase

Explanation

Thrombotic thrombocytopenic purpura results from deficiency of ADAMTS13, a metalloprotease that cleaves ultralarge multimers of von Willebrand factor. Accumulated ultralarge multimers cause widespread platelet-rich microthrombi, producing the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurologic signs, renal involvement, and fever. Shiga toxin injury defines typical HUS, seen in children after diarrheal illness, whereas this adult has preserved renal function, favoring TTP.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.