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warfarin-induced epidermal necrosis
Etiology: (risk factors)
1) higher initial dosing
2) hereditary deficiency of protein C
3) protein S deficiency
4) antithrombin 3 deficiency
Epidemiology:
1) 1 in 10,000 warfarin-treated patients
- occurs even less frequently in ambulatory patients
2) middle-age to elderly
3) females > males, especially if obese
Pathology:
1) epidermal necrosis
2) thrombosis & occlusion of blood vessels
3) weak inflammatory response
4) 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
5) lesions may subside or heal by granulation
Clinical manifestations:
1) generally occurs between 3rd & 5th days of anticoagulation with warfarin
2) lesions vary with severity of reaction
- petechiae, ecchymoses, hemorrhagic infarcts, extensive necrosis
3) early lesions: large, red, indurated plaques
4) later lesions: well demarcated, violaceous to black geographic areas of necrosis
5) hemorrhagic bullae & large erosions may complicate infarcts
6) late: tissue sloughing & ulceration if lesions are not debrided & grafted
7) lesions are tender & painful
8) lesions occur on areas of abundant adipose tissue
a) breasts, buttocks, abdomen, thighs, calves
b) acral areas are spared
Laboratory:
1) coagulation studies usually within normal limits
2) protein C assay is a functional assay, thus NOT useful in anticoagulated patient
Differential diagnosis:
1) purpura fulminans (disseminated intravascular coagulation)
2) hematoma/ecchymosis in overly anticoagulated patient
3) necrotizing soft tissue infection
4) vasculitis
5) brown recluse spider bite
6) heparin necrosis (injection site)
Management:
1) discontinue warfarin
2) administer vitamin K
3) substitute heparin or LMW heparin as anticoagulant
4) administer protein C concentrate to protein C deficient patient
5) treat necrotic tissue as 3rd degree burn
6) debride necrotic tissue
7) graft debrided site
8) prevention
a) medical alert bracelet
b) 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 [2]
9) prognosis: may be life threatening in debilitated patient
References
- Color Atlas & Synopsis of Clinical Dermatology, Common
& Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY,
1997, pg 600-602
- Hoffman, Hematology: Basic Principles and Practice, 3rd ed.,
Churchill Livingstone Inc., 2000, page 2045
http://home.mdconsult.com/das/book/37126987-2/view/1053?sid=265514817