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Warfarin Calciphylaxis MGP Mechanism — ESENeph MCQ

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HardHaemodialysisWarfarin Calciphylaxis MGP MechanismESENeph

A 72-year-old woman with CKD G5D on haemodialysis has been on long-term warfarin for a mechanical mitral valve replacement. She develops painful purple skin lesions on her abdomen and thighs. Biopsy shows calcification of small dermal arterioles. INR is 4.2. What role does warfarin play in this condition?

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Correct answer: D — Warfarin inhibits matrix Gla protein carboxylation, promoting vascular calcification

Warfarin is an independent risk factor for calciphylaxis. Warfarin inhibits vitamin K-dependent gamma-carboxylation of matrix Gla protein (MGP) — a potent local inhibitor of vascular calcification. Uncarboxylated MGP cannot function as a calcification inhibitor, promoting calcium deposition in vessel walls. In dialysis patients who already have disturbed calcium-phosphate metabolism, warfarin-induced loss of MGP function accelerates calciphylaxis development. Management includes: stopping warfarin (switching to an alternative anticoagulant — DOACs are not licensed for mechanical valves, so heparin bridging/discussion with cardiology is needed), starting vitamin K supplementation, sodium thiosulphate, and wound care.

Reference: Nigwekar et al 2018 – Calciphylaxis NEJM; Krueger et al 2009 – Matrix Gla Protein and Warfarin