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Coagulation

Therapy related coagulopathies

Warfarin (Coumadin™)


Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 12 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Therapeutic anticoagulant to prevent thromboembolism by impairing regeneration of active vitamin K (warfarin is a synthetic derivation based on coumarin)
● The name incorporates the acronym for the organization which funded the key research (WARF, for Wisconsin Alumni Research Foundation) and the ending -arin, indicating its link with coumarin

Pathophysiology
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● Vitamin K is a cofactor in reactions that carboxylate glutamic acid residues in factors II, VII, IX, X, protein C, protein S
● These “GLA” domains enable the coagulation factors to bind to phospholipid membranes in the presence of calcium
● Therapeutic warfarin or Vitamin K deficiency cause decreased activity of these proteins, making the enzymes less able to participate in the clotting cascade, which prolongs the PT

Clinical features
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● Takes 4-5 days for complete therapeutic effect due to long half-life of factors II and X
● Must be supplemented with another anticoagulant such as heparin (“bridged”) until INR is in therapeutic range for 2 consecutive days to prevent Warfarin Skin Necrosis in those with low Protein C
● Therapeutic effect is measured by INR - goal is often INR between 2 and 3
● INR may be elevated by lupus anticoagulants or use of hirudin with warfarin
● Warfarin should not be used alone for acute heparin-induced thrombocytopenia because it causes paradoxical thrombosis - must add a rapid acting anticoagulant (hirudin, danaparoid, argatroban) until INR is therapeutic
● Note: PTT may be normal if low warfarin levels

Treatment of bleeding/overdose:
● Vitamin K, fresh frozen plasma; also prothrombin complex concentrates (J Clin Pathol 2004;57:1132, J Thromb Haemost 2006;4:1853)

Diagrams
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Biochemistry of coumarins

End of Coagulation > Therapy related coagulopathies > Warfarin (Coumadin™)


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