Low Dose Prothrombin Complex Concentrates Reverse Oral Anticoagulation with Minimal Complications.

Prothrombin complex concentrate (PCC) is widely used for the reversal of warfarin in the context of life threatening haemorrhage or emergency surgery. For these indications, it is considered superior to fresh frozen plasma (FFP), in terms of viral safety, efficacy and speed of administration. Dosage of PCCs for coumarin reversal (30–50IU/kg) is based on that required for patients with haemophilia B. This dose is frequently associated with thrombosis, particularly in the presence of liver disease. Factors underlying the prothrombotic potential of PCCs include the activation of clotting factors during the manufacturing process, coexisting co morbidities in the patient and repeated administration leading to clotting factor accumulation in vivo. The risk of thrombosis has led to a reluctance to administer PCCs, despite proven efficacy, in patients with arterial or venous thromboembolism, sepsis and liver disease. Recent work suggests that PCCs can effectively reverse anticoagulation when administered in much lower doses. We collected data on 38 patients (mean age 70 years) who received Beriplex (Aventis Behring) to reverse anticoagulation either for life threatening haemorrhage or emergency surgery. Patients were receiving warfarin for atrial fibrillation (50%), recurrent thromboembolic disease (18.5%) and mechanical heart valves (13%). 52.5% received Beriplex following haemorrhage, 26.5% to correct the INR prior to emergency surgery and 2.5% for an excessively elevated INR. 87.6% received 500IU Beriplex with the remainder receiving 1000IU. Of 38 patients, 18 out of 29 received Vitamin K. Mean INR fell significantly (p<0.01) following Beriplex administration (mean INR pre-Beriplex 4.8, post-Beriplex 1.8). 81% had an INR <2 following Beriplex. Of patients with an INR <8 receiving one vial, 64% corrected their INR to <1.4 (96% patients had an INR <2). 59% of patients had additional risk factors including ischaemic heart disease, recurrent thromboembolism, sepsis or abnormal liver function. No patients had thrombotic complications. Three had evidence of DIC following administration of Beriplex, all in association with sepsis and no patient experienced bleeding complications at the time of surgery. Bleeding was well controlled in those experiencing life threatening haemorrhage except in two patients, who presented with massive intracranial bleeds. This data indicates that PCCs should be considered in all patients on warfarin who require urgent anticoagulation reversal, at a dose of 500IU only. PCCs at a fixed low dose appear to correct anticoagulation effectively based on both clinical and laboratory parameters, without the need for repeated administration. Importantly, PCCs at this lower dose were not associated with thromboembolic events. Low dose PCCs therefore provide patients with a safe and effective antidote to warfarin.