The Efficacy and Safety of PPSSB (Human Prothrombin Complex) for Reversal of Oral Anticoagulation.

Abstract

Oral anticoagulant use is increasing and along with it, the risk of bleeding complications. Protocols for reversal of vitamin K antagonists are not standardised with current treatment options including fresh frozen plasma (FFP), vitamin K and Human Prothrombin complex (PPSB). The advantages of PPSB over FFP include rapid reconstitution and administration, additional viral inactivation steps and high concentration of factors within a small volume. However PPSB is expensive, has putative thrombogenicity at high doses and the optimum dose has yet to be clarified. We performed a single centre, retrospective study using medical and laboratory records to look at the indications, doses used, efficacy and safety of PPSB, a plasma derived, virally inactivated concentrate, in patients who had required reversal of the oral vitamin K antagonists (VKA) warfarin and phenindione. 36 patients (16 female, 20 male) had been treated over a 2 year period with a median age of 60years (19–83). Indications for administration were reversal of VKA for a procedure or surgery (10 patients), for bleeding (7 patients) and a high international normalised ratio (INR) without bleeding (19 patients). The median dose of PPSB was 500 units (250–1000 units) of factor IX activity with 75% patients receiving this dose. Mean pre-and post-treatment INRs were: 250 units 7.38 and 2.04; 500 units 7.08 and 2.03; 1000 units 11.87 and 1.70Reduction in INR according to initial INRInitial INR>8Initial INR<8Mean pre treatment INR11.26 (10–16.4)3.95* (1.6–7.85)Mean post treatment INR2.15 (1.18–3.29)1.74 (1.2–3.3)Mean reduction in INR (%)80.6 (71–88)48.65 (15–77)*INR outside therapeutic range for all patientsThe mean INR was reduced from 10.7 to 2.3 for isolated high INR, from 6.8 to 1.8 for those patients who were bleeding and from 2.7 to 1.4 for those undergoing a procedure or surgery. Concomitant vitamin K use had not clearly been documented. There were no thrombotic complications and adequate haemostasis was achieved in all the patients who were bleeding however one patient undergoing surgery developed a small haematoma. Previous evidence has shown PPSB to be effective in reversing the effects of VKA in life threatening bleeding however this study demonstrates that it may also be an efficacious treatment in the outpatient setting (in conjunction with vitamin K) for those with an uncomplicated high INR. Traditional dosing methods of PPSB have been on weight [dose = weight x (desired IX-actual IX)] but in this study adequate INR reduction had been achieved with smaller doses, particularly in those patients who were not bleeding and required continuation of VKA therapy. This is important in the context of avoiding thrombotic complications. Laboratory data suggests that in warfarin overdose, the reduction in factor IX activity( IX:C) plateaus out beyond an INR of 8–10 which may explain the greater reduction in INR for the same dose with a higher initial INR (table 1).