Urgent reversal of warfarin with prothrombin complex concentrate

Abstract

Summary. Background: When life-threatening bleeding occurs in patients on warfarin, timely reversal becomes imperative. In the USA, warfarin effect is commonly reversed with fresh frozen plasma (FFP). The use of FFP is complicated by delays in correction, volume overload and often, inadequate correction. Objective: Evaluate the feasibility and efficacy of a protocol for rapid administration of prothrombin complex concentrate (PCC) in the setting of the urgent need for reversal of warfarin. Methods/patients: We instituted a policy for rapid delivery and administration of PCC. Appropriate patients received 25-50 U kg )1 of PCC. The prothrombin time (PT)/International Normalized Ratios (INR) was recorded before and immediately after dosing, and 24 h postdosing. Patients requiring surgical interventions were cleared for the operating room (OR) immediately. Fifty-eight patients were treated, with a median age of 75.5 years (range 26-92). Results: The median INR on presentation was 3.8 (1.4-52.8). Immediately following PCC administration the median INR was 1.3 (0.9-5.7), only two patients with INRs exceeding 2.0. The benefit was maintained at 24 h with a median INR of 1.5 (1.1-3.4). Four patients experienced thrombotic events during their hospitalization, (two deep vein thrombosis, two non-q-wave myocardial infarction) although none was attributed to PPC therapy. Conclusions: PCC administration is an effective treatment modality for the correction of warfarin anticoagulation in the urgent setting. Advantages over FFP include more timely correction, absence of volume overload and potentially more complete correction. Broader use of PCC in this setting appears to be appropriate.

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

“…There were, however, seven thrombotic complications (that is, 1.5% of patients experienced a thrombotic event). Four of these, two deep vein thromboses and two non-ST elevation myocardial infarctions which were identified in a retrospective review of 58 patients, were not attributed to PCC therapy [15]. Two thrombotic strokes occurred in patients with extensive co-morbidities [16].…”

Approach to and management of the acute stroke patient with atrial fibrillation: A literature review

“…42 In general, 10 to 15 cc/kg FFP is used. 43 Timing rather than dosage seems to be more important for a better clinical outcome.…”

“…44,46 Therefore, a PCC dose of 25 to 59 U/kg has been used in life-threatening bleeding, resulting in a decrease in the median INR from 3.8 to 1.3 immediately after administration. 42 PCCs should always be given with vitamin K. Thrombotic events have been described with the infusion of PCCs, but no clear guidelines have been published. 42 A recent study from the Mayo Clinic showed that many experts suggest its use in the urgent condition of warfarin-associated ICH.…”

“…42 PCCs should always be given with vitamin K. Thrombotic events have been described with the infusion of PCCs, but no clear guidelines have been published. 42 A recent study from the Mayo Clinic showed that many experts suggest its use in the urgent condition of warfarin-associated ICH. 41 PCCs are widely used in the European community and have previously been cited as the agent of choice for urgent warfarin reversal.…”

“…41 PCCs are widely used in the European community and have previously been cited as the agent of choice for urgent warfarin reversal. 42,47,48 A recent study comparing PCCs with FFP and vitamin K has demonstrated that PCCs may be superior to FFP and vitamin K by reducing the risk of hematoma growth. 49 Recombinant Factor VIIa Recombinant factor VIIa is a preparation of activated coagulation factor VII (factor VIIa) that is produced by recombinant DNA technology.…”