Warfarin necrosis

cascade. Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development. activated protein C resistance (Factor V Leiden) and antithrombin III deficiency. Although the above hypothesis is the most commonly accepted, others believe that it is a hypersensitivity reaction or a direct toxic effect. ==Diagnosis==

Differential diagnosis Many conditions mimic or may be mistaken for warfarin necrosis, including pyoderma gangrenosum or necrotizing fasciitis. Warfarin necrosis is also different from another drug eruption associated with warfarin, purple toe syndrome, which usually occurs three to eight weeks after the start of anticoagulation therapy. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency. ==Prevention==

Vitamin K1 can be used to reverse the effects of warfarin, and heparin or its low molecular weight heparin (LMWH) can be used in an attempt to prevent further clotting. None of these suggested therapies have been studied in clinical trials. Heparin and LMWH act by a different mechanism than warfarin, so these drugs can also be used to prevent clotting during the first few days of warfarin therapy and thus prevent warfarin necrosis (this is called 'bridging'). ==Treatment==

The first element of treatment is usually to discontinue the offending drug, although there have been reports describing how the eruption evolved little after it had established in spite of continuing the medication. Since the clot-promoting effects of starting administration of 4-hydroxycoumarins are transitory, patients with protein C deficiency or previous warfarin necrosis can still be restarted on these drugs if appropriate measures are taken. These include gradual increase starting from low doses and supplemental administration of protein C (pure or from fresh frozen plasma). The necrotic skin areas are treated as in other conditions, sometimes healing spontaneously with or without scarring, sometimes going on to require surgical debridement or skin grafting. ==History==

While skin necrosis in patients had been previously described, Verhagen was the first to publish a paper on this relationship in the medical literature, in 1954. == See also ==