Reversal of Elevated International Normalized Ratios and Bleeding with Low-Dose Recombinant Activated Factor VII in Patients Receiving Warfarin

• Published in: Pharmacotherapy Vol. 26; no. 8; pp. 1091 - 1098
• Main Authors: Dager, William E., King, Jeff H., Regalia, Ron C., Williamson, Dean, Gosselin, Robert C., White, Richard H., Tharratt, R. Steven, Albertson, Timothy E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2006; Pharmacotherapy
• Subjects: Adolescent; Aged; Aged, 80 and over; Anticoagulants - adverse effects; anticoagulation reversal; Biological and medical sciences; bleeding; Blood Coagulation - drug effects; Coagulants - administration & dosage; Critical Care; Factor VII - administration & dosage; Factor VIIa; Female; fresh frozen plasma; Hemorrhage - blood; Hemorrhage - chemically induced; Hemorrhage - drug therapy; Humans; INR; International Normalized Ratio; intracranial hemorrhage; Male; Medical sciences; Middle Aged; Neurology; NOVOSEVEN; Prospective Studies; recombinant activated factor VII; Recombinant Proteins - administration & dosage; rFVIIa; trauma; Vascular diseases and vascular malformations of the nervous system; warfarin; Warfarin - adverse effects; Biological fluid; bleeding; Coumarine derivatives; Cardiovascular disease; Intracranial hemorrhage; Anticoagulant; INR; Blood plasma; Vascular disease; Antivitamin K; fresh frozen plasma; Recombinant protein; NOVOSEVEN; Cerebrovascular disease; Coagulation Factor VIIa; Human; Nervous system diseases; Warfarin; Serine endopeptidases; Enzyme; Low dose; Trauma; Cerebral disorder; recombinant activated factor VII; Peptidases; Treatment; rFVIIa; Central nervous system disease; International normalized ratio; anticoagulation reversal; Hydrolases; Reversibility; Coagulation factor
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1592/phco.26.8.1091

Study Objective. To assess the effectiveness of using low‐dose recombinant activated factor VII (rFVIIa) to reverse the effects of warfarin in critically ill patients with major bleeding events.
Design. Prospective observational study.
Setting. Intensive care unit of a 500‐bed university‐affiliated hospital.
Patients. Sixteen nonhemophiliac patients who had been receiving warfarin and had an acute major bleeding event.
Intervention. Patients received rFVIIa 1.2 mg for reversal of anticoagulation.
Measurements and Main Results. Patients were identified from clinical pharmacology consult service electronic tracking records, and their data were cross‐checked with the pharmacy information system. Information collected for each patient included extent of bleeding and magnitude of elevation in international normalized ratio (INR). A mean ± SD dose of rFVIIa 16.3 ± 4.1 μg/kg (range 11–25 μg/kg) reduced the mean INR from 2.8 ± 1.6 (range 1.44–6.34) to 1.07 ± 0.27 (range 0.86–1.92, p<0.001). A rapid onset of response for achieving a desirable hemostatic effect was observed in 14 of the 16 patients.
Conclusion. Low‐dose rFVIIa appears to be an effective, rapid reversal modality for major bleeding events in the presence of warfarin and an elevated INR. The agent's response is quicker than that expected with fresh frozen plasma combined with vitamin K. In emergency situations, rFVIIa 1.2 mg can be used to reverse the anticoagulant effect of warfarin and other vitamin K antagonists without inducing a hypercoagulable state; the product, however, is expensive.