Emergency Oral Anticoagulant Reversal: The Relative Efficacy of Infusions of Fresh Frozen Plasma and Clotting Factor Concentrate on Correction of the Coagulopathy

Abstract

SummaryHaemorrhage, including intracranial bleeding, is a common, potentially lethal complication of warfarin therapy and rapid and complete reversal of anticoagulation may be life-saving. Fresh frozen plasma (FFP) and vitamin K are most frequently administered. Because of the variable content of vitamin K-dependent clotting factors in FFP, and the effects of dilution, the efficacy of this approach is open to doubt. We have therefore compared the effects of FFP and clotting factor concentrates on the INRs and clotting factor levels of orally anticoagulated subjects requiring rapid correction of their haemostatic defect. In many, the pre-treatment INR was considered to be dangerously above the target therapeutic range. In the 12 patients given FFP, the INR did not completely correct (range 1.6-3.8, mean 2.3) indicating an ongoing anticoagulated state in all. In contrast, the INR in 29 subjects given clotting factor concentrates was completely corrected in 28 (range 0.9-3.8, mean 1.3). Following treatment, marked differences were observed in clotting factor IX levels between the two groups. The median factor IX level was 19 u/dl (range 10-63) following FFP infusion and 68.5 u/dl (range 31-111) following concentrate. In FFP treated patients, poorer responses were also observed for each of the other vitamin K-depen- dent clotting factors but these were less marked than for factor IX, which was present in low concentrations in some batches of FFP. Thus, haemostatically effective levels of factor IX cannot be achieved, in most instances, by the conventional use of FFP in patients requiring reversal of their anticoagulant therapy. Clotting factor concentrates are the only effective option where complete and immediate correction of the coagulation defect is indicated in orally anticoagulated patients with life or limb-threatening haemorrhage.

Pharmacologic Reversal of Warfarin-Associated Coagulopathy in Geriatric Patients With Hip Fractures

“…29 Fresh frozen plasma is an alternative to vitamin K for correcting coagulopathy, which may be administered to reverse the effects of warfarin. [30][31][32][33][34][35] Fresh frozen plasma is a human donor plasma that contains many plasma proteins, including all the coagulation factors, and has been the most widely utilized form of coagulation factor replacement. 36 However, because of the variable content of the vitamin K-dependent coagulation factors in FFP, especially factor IX, large volumes of fluid required, and the increased infection risks, the use of FFP for the emergency reversal of warfarin coagulopathy has been questioned.…”

“…36 However, because of the variable content of the vitamin K-dependent coagulation factors in FFP, especially factor IX, large volumes of fluid required, and the increased infection risks, the use of FFP for the emergency reversal of warfarin coagulopathy has been questioned. [30][31][32] Recently published evidence-based practice guidelines for FFP transfusion fail to recommend for or against transfusion to reverse warfarin coagulopathy in patients without intracranial hemorrhage, as the quality of evidence on both sides is very low. 33 Some evidence exists to suggest that overly aggressive pharmacologic reversal of supratherapeutic INRs may promote thromboembolic events and other complications.…”

Reversal of vitamin K antagonists prior to urgent surgery

“…However, there have been several small trials in patients with intra-cerebral hemorrhages that demonstrate a more complete reversal of the INR with PCC. 48,49 In addition, PCC may be a more reliable source of FIX that is not assessed with the PT/INR test and yet may be particularly important in hemostasis. 50 Until now, evidence of improved outcomes or better control of bleeding risk is unavailable, but data may be available on the completion of the FDA required studies comparing FP with BeriplexÒ for patients with major bleeding due to warfarin toxicity.…”

Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate

“…Coumarins inhibit the maturation of functional vitamin K-dependent coagulation factors II (FII), VII (FVII), IX (FIX), and X (FX), and hence cause a functional deficiency of these proteins. Both FFP and PCC can restore the levels of these four coagulation factors, but PCC can reverse warfarin-related coagulopathy more rapidly than FFP, and usually more completely [10][11][12]. FFP is more cumbersome and slower to administer than PCC.…”