title: Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.
abstract: Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA.
authors.affiliation: University of Tennessee Health Science Center, Department of Clinical Pharmacy, and Methodist University Hospital, Memphis, TN. Electronic address: tself@uthsc.edu.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Self
authors.affiliation: Methodist University Hospital, Department of Pharmacy, and University of Tennessee Health Science Center.
authors.forename: Carrie S
authors.initials: CS
authors.lastname: Oliphant
authors.affiliation: Methodist University Hospital, Department of Pharmacy, and University of Tennessee Health Science Center.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Reaves
authors.affiliation: University of Tennessee Health Science Center, Department of Clinical Pharmacy, and Methodist University Hospital, Memphis, TN.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Richardson
authors.affiliation: Methodist University Hospital, Methodist Inpatient Physicians, and University of Tennessee Health Science Center.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Sands
mesh_terms: D000074:Acenocoumarol / Q000627:therapeutic use; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003374:Coumarins / Q000627:therapeutic use; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology*; D006470:Hemorrhage; D006801:Humans; D019934:International Normalized Ratio; D010644:Phenprocoumon / Q000627:therapeutic use; D051381:Rats; D012307:Risk Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D014812:Vitamin K; D014859:Warfarin; C030123:coumarin; D000074:Acenocoumarol; D010644:Phenprocoumon
keywords: Coumarin anticoagulants; Fever; Mechanisms; Vitamin K antagonists; Warfarin