Original contributionRecombinant factor VIIa for warfarin-associated intracranial bleeding
Introduction
Patients receiving warfarin are at increased risk for intracranial hemorrhage (ICH). Stopping these acute bleeds from turning into chronic disability requires prompt treatment [1], [2], [3], [4], [5], [6], [7]. In a typical scenario, an elderly patient taking warfarin for atrial fibrillation falls and sustains a head injury [8]. In the emergency department, the risk and symptoms are recognized, imaging studies confirm ICH, and therapy with vitamin K and thawed plasma is begun. However, vitamin K does not work quickly, and the large doses of plasma necessary to reverse the coagulopathy are frequently not tolerated by these older patients [9], [10]. If given quickly, plasma can precipitate congestive heart failure and the need for ventilatory support; if it is given slowly, there is a greater risk of hemorrhage progression. Prothrombin complex concentrates are recommended in this situation because of their lower volume, but the only such concentrates available in the United States (eg, FEIBA, AutoPlex, or ProPlex; Baxter Healthcare Corp, Westlake Village, CA) are preactivated by the manufacturing process and carry risks of thrombotic and allergic complications [11], [12], [13], [14], [15].
Recombinant coagulation factor VIIa (rVIIa) has been considered for use in this situation because it promptly corrects the International Normalized Ratio (INR) and appears to stop the bleeding [15], [16], [17], [18], [19]. However, its use has been challenged because it provides only a partial correction of the bleeding diathesis as it corrects the Factor deficiency but not the reduced concentrations of other vitamin K–dependent factors II, IX, and X.
We reviewed 7 years of experience at a major trauma center with patients taking warfarin who were injured and who sustained intracranial bleeds. In the last three years, most such patients were treated with rVIIa. The speed with which the INR was corrected, the duration of correction of the INR, the relation of the duration of correction to drug dose, and the effect of correction on patient outcome were determined.
Section snippets
Materials and methods
With permission of the University of Maryland School of Medicine Institutional Review Board, we accessed the ongoing quality management database of patients who valued customer received rVIIa while at the R. Adams Cowley Shock Trauma Center (STC). This database was reviewed for all patients who had been taking warfarin and who presented with a new or evolving intracranial bleed. With separate permission, we queried the STC's Trauma Registry for calendar years 2000 to 2004 for patients who
Results
Twenty-four patients were identified who presented to STC with a history of receiving warfarin, an INR greater than 1.4, a new intracranial bleeding event, and who were treated with rVIIa. The doses of rVIIa used ranged from 10 to 100 μg/kg, with lower doses used in the more recent patients. Thirty control patients were identified in the STC Trauma Database from 2000 to 2004 who also presented with a new intracranial bleeding event, a history of receiving warfarin, and an INR greater than 1.4.
Discussion
As the population ages, an increasing number of individuals are taking warfarin for the prevention of thromboembolic complications of atrial fibrillation, cardiac valve replacement, deep venous thrombosis, and thrombophilic states [3]. These individuals are at increased risk for ICH, which can arise spontaneously or be secondary to trauma [1], [2], [4].
In a review of blood usage at STC, 20 such patients accounted for 4% of all patients who received blood products among 5,645 direct admissions
References (22)
- et al.
Framingham Heart Study. Warfarin and aspirin use and the predictors of major bleeding complications in arterial fibrillation (the Framingham Heart Study)
Am J Cardiol
(2004) - et al.
Time trends in warfarin-associated hemorrhage
Am J Cardiol
(2004) - et al.
Oral-anticoagulant–related intracerebral hemorrhage
Thromb Res
(2002) - et al.
Correction of INR by prothrombin complex concentrates and vitamin K in patients with warfarin related hemorrhagic complications
Thromb Res
(2002) - et al.
Recombinant factor VIIa for rapid reversal of warfarin anticoagulation in acute intracranial hemorrhage
Mayo Clin Proc
(2004) - et al.
The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest
(2004) - et al.
The increasing incidence of anticoagulant-associated intracerebral hemorrhage
Neurology
(2007) - et al.
The impact of antithrombotic therapy on neurosurgical emergency referral load
Ir Med J
(2006) - et al.
Intracranial bleeding: epidemiology and relationships with antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia
Haematologica
(2002) - et al.
Complications of preinjury warfarin use in the trauma patient
J Trauma
(2003)
Rapid warfarin reversal in anticoagulated patients with traumatic brain injury reduces hemorrhage progression and mortality
J Trauma
Cited by (60)
Anticoagulant Reversal and Anesthetic Considerations
2017, Anesthesiology ClinicsTherapy for acute cerebral haemorrhages under anticoagulation
2021, ArzneimitteltherapieHemostatic agents and blood components used to stop bleeding
2021, Management of Bleeding PatientsIntracerebral hemorrhage: An overview of etiology, pathophysiology, clinical presentation, and advanced treatment strategies
2021, Management of Bleeding Patients