warfarin-induced epidermal necrosis

Etiology

(risk factors)

• higher initial dosing
• hereditary deficiency of protein C
• protein S deficiency
• antithrombin 3 deficiency

Epidemiology

• 1 in 10,000 warfarin-treated patients
  • occurs even less frequently in ambulatory patients
• middle-age to elderly
• females > males, especially if obese

Pathology

• epidermal necrosis
• thrombosis & occlusion of blood vessels
• weak inflammatory response
• in individuals with protein C deficiency, warfarin reduces protein C levels further before diminishing other vitamin K-dependent clotting factors, inducing a transient hypercoagulable state & thrombosis
• lesions may subside or heal by granulation

Clinical manifestations

• generally occurs between 3rd & 5th days of anticoagulation with warfarin
• lesions vary with severity of reaction
  • petechiae, ecchymoses, hemorrhagic infarcts, extensive necrosis
• early lesions: large, red, indurated plaques
• later lesions: well demarcated, violaceous to black geographic areas of necrosis
• hemorrhagic bullae & large erosions may complicate infarcts
• late: tissue sloughing & ulceration if lesions are not debrided & grafted
• lesions are tender & painful
• lesions occur on areas of abundant adipose tissue
  • breasts, buttocks, abdomen, thighs, calves
  • acral areas are spared

Laboratory

• coagulation studies usually within normal limits
• protein C assay is a functional assay, thus NOT useful in anticoagulated patient

Differential diagnosis

• purpura fulminans (disseminated intravascular coagulation)
• hematoma/ecchymosis in overly anticoagulated patient
• necrotizing soft tissue infection
• vasculitis
• brown recluse spider bite
• heparin necrosis (injection site)

Management

• discontinue warfarin
• administer vitamin K
• substitute heparin or LMW heparin as anticoagulant
• administer protein C concentrate to protein C deficient patient
• treat necrotic tissue as 3rd degree burn
• debride necrotic tissue
• graft debrided site
• prevention
  • medical alert bracelet
  • suggestion made that protein C deficiency may occur with initiation of warfarin administration in patients heterozygous for a defect in the gene for protein C, but that the risk of skin necrosis is attenuated by anticoagulation with heparin
• prognosis: may be life threatening in debilitated patient