title: Venous limb gangrene during warfarin treatment of cancer-associated deep venous thrombosis.
abstract: BACKGROUND
  The cause of cancer-associated venous limb gangrene is unknown but could paradoxically be due to warfarin.
  
  
  OBJECTIVE
  To determine the pathogenesis of venous gangrene in a patient with cancer.
  
  
  METHODS
  Case report.
  
  
  METHODS
  University hospital in Ontario, Canada.
  
  
  METHODS
  66-year-old woman with metastatic lung cancer and deep venous thrombosis.
  
  
  METHODS
  Levels of vitamin K-dependent factors, additional coagulation factors, and thrombin-antithrombin complexes (marker of thrombin generation).
  
  
  RESULTS
  During warfarin use, venous limb gangrene developed when the international normalized ratio (INR) reached 6.0 (therapeutic range, 2.0 to 3.0); at this time, the level of protein C (a vitamin K-dependent natural anticoagulant) was severely reduced, but thrombin-antithrombin complexes remained markedly elevated. The supratherapeutic INR was explained by the greatly reduced levels of factor VII, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity.
  
  
  CONCLUSIONS
  Warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein C while at the same time failing to reduce thrombin generation.
authors.affiliation: McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: T E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D000936:Antigen-Antibody Complex / Q000097:blood; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D001779:Blood Coagulation Factors / Q000378:metabolism; D005260:Female; D005734:Gangrene / Q000139:chemically induced*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000150:complications*; D020151:Protein C Deficiency / Q000139:chemically induced*; D013917:Thrombin / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced*; D020246:Venous Thrombosis / Q000209:etiology / Q000473:pathology*; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D000936:Antigen-Antibody Complex; D001779:Blood Coagulation Factors; D014859:Warfarin; D013917:Thrombin