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Publications

Published: 7 September 2017

Warfarin and Calciphylaxis — A Rare but Serious Adverse Event

Prescriber Update 38(3): 38-39
September 2017

Key Messages

  • Calciphylaxis is a very rare but serious condition most commonly observed in patients with known risk factors such as end-stage renal disease.
  • Calciphylaxis has been reported in patients taking warfarin, including those with normal renal function.
  • Patients treated with warfarin should be advised to consult their doctor if they develop a painful rash/ulcer.
  • If calciphylaxis is diagnosed, appropriate treatment should be started and consideration should be given to stopping treatment with warfarin.

 

Calciphylaxis is a very rare but serious condition characterised by vascular calcification and cutaneous necrosis. Calciphylaxis has been reported in patients taking warfarin1. These patients commonly had pre-existing renal disease, but some reports noted normal renal function1.

The Centre for Adverse Reactions Monitoring (CARM) has received two reports of calciphylaxis associated with the use of warfarin. Both patients were reported to have multiple comorbidities, including severe chronic renal failure in the first case and stage 4 chronic kidney disease in the second case.

Calciphylaxis is generally seen in patients with end-stage renal disease on dialysis or in those with known risk factors such as protein C or S deficiency, hyperphosphataemia, hypercalcaemia or hypoalbuminaemia1.

The exact pathogenesis of calciphylaxis is unknown. Small blood vessels deep in the skin become blocked due to calcification and thrombosis. The resulting skin lesions are typically purpuric, indurated plaques with central necrosis.

Patients with calciphylaxis usually experience severe pain, burning and sometimes itching at lesion sites. The mortality rate is very high, primarily caused by secondary infection of the ulcers and sepsis2.

The mechanism by which warfarin causes calciphylaxis may be mediated through the matrix Gla protein, which is a vitamin-K-dependent protein that prevents calcium deposition in arteries. Warfarin inhibits Gla protein and may therefore promote vascular calcification in susceptible individuals1.

The authors of a recent review suggest that warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course and particularly outcome as the survival rate of nonuremic patients was remarkably high (83%)3.

Medsafe is working to ensure that all data sheets for warfarin products include calciphylaxis as a potential adverse effect.

References
  1. Medicines and Healthcare Products Regulatory Agency. 2016. Calciphylaxis is a very rare but serious condition causing vascular calcification and skin necrosis. Drug Safety Update. 18 July 2016. URL: gov.uk/drug-safety-update/warfarin-reports-of-calciphylaxis (accessed 27 June 2017).
  2. Larsen F, Oakley A, 2016. Calciphylaxis. DermNet New Zealand. February 2016. URL: dermnetnz.org/topics/calciphylaxis (accessed 28 July 2017).
  3. Yu WY, Bhutani T, Kornik R, et al. 2017. Warfarin-Associated Nonuremic Calciphylaxis. JAMA Dermatology 153(3): 309–14.
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