title: Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT.
  
  
  METHODS
  We describe 6 patients with HIT seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation.
  
  
  RESULTS
  At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died.
  
  
  CONCLUSIONS
  Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.
authors.affiliation: Section of Hematology-Oncology, Department of Medicine, Baylor College of Medicine, Houston, Tex. 77030, USA.
authors.forename: Abhay F
authors.initials: AF
authors.lastname: Srinivasan
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rice
authors.forename: John R
authors.initials: JR
authors.lastname: Bartholomew
authors.forename: Chandhiran
authors.initials: C
authors.lastname: Rangaswamy
authors.forename: Lucy
authors.initials: L
authors.lastname: La Perna
authors.forename: James E
authors.initials: JE
authors.lastname: Thompson
authors.forename: Scott
authors.initials: S
authors.lastname: Murphy
authors.forename: Kelty R
authors.initials: KR
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D005260:Female; D005734:Gangrene / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D007866:Leg / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006493:Heparin