A 40-year-old woman with paroxysmal nocturnal hemoglobinuria (PNH) develops sudden-onset severe abdominal pain. The pathophysiologic mechanism of thrombosis in PNH directly involves:
- A Elevated plasma free hemoglobin scavenging nitric oxide and causing venous endothelial vasoconstriction
- B PIG-A mutation causing loss of GPI-anchored CD55 and CD59, leading to complement-driven platelet activation and release of prothrombotic microparticles ✓
- C Deficiency of ADAMTS13 causing ultralarge vWF multimer accumulation and platelet thrombi
- D JAK2 V617F mutation causing myeloproliferative thrombocytosis
Explanation
PNH is caused by somatic PIG-A mutations that impair GPI anchor biosynthesis, resulting in loss of all GPI-anchored proteins including CD55 (DAF) and CD59 (protectin) from blood cell surfaces. Without these complement regulatory proteins, PNH clones undergo uncontrolled complement-mediated lysis and platelet activation. Activated PNH platelets release prothrombotic microparticles rich in phosphatidylserine and tissue factor, driving a hypercoagulable state especially in hepatic, portal, mesenteric, and cerebral veins. Hemoglobin-mediated NO scavenging also contributes to thrombosis but is a secondary mechanism. ADAMTS13 deficiency causes TTP. JAK2 mutation causes myeloproliferative disorders.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.