Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding

Abstract

Introduction: Prothrombin complex concentrates are recommended for rapid reversal of vitamin K anticoagulants. As they normalize levels of vitamin K dependent clotting factors and re-establish hemostasis, they may also be used as adjunctive therapy in patients with major bleeding. The aim of this study was to retrospectively evaluate the efficacy of prothrombin complex concentrates in the surgical setting.

Methods: The case notes of 50 patients requiring urgent oral anticoagulation reversal (n = 12) or with severe perioperative coagulopathic bleeding (n = 38) who received an infusion of prothrombin complex concentrate (Beriplex P/N(R) 500) at the surgical department of the University of Munich Hospital, Germany were retrospectively reviewed. Efficacy of prothrombin complex concentrate application was evaluated using the Quick test, reported as an international normalized ratio, hemodynamic measurements and requirement for blood products. Safety assessments included whole blood hemoglobin levels and specific parameters of organ dysfunction.

Results: Baseline characteristics were comparable, except that mean baseline international normalized ratio and hemoglobin levels were significantly higher (P < 0.01) in anticoagulation reversal than in bleeding patients. In anticoagulation reversal, the international normalized ratio was significantly reduced (from 2.8 +/- 0.2 at baseline to 1.5 +/- 0.1, P < 0.001) after one prothrombin complex concentrate infusion (median dose 1500 IU; lower quartile 1,000, upper quartile 2,000). No major bleeding was observed during surgery after prothrombin complex concentrate administration. Only one patient received platelets and red blood cell transfusion after prothrombin complex concentrate administration. In bleeding patients, infusion of prothrombin complex concentrate (median dose 2,000 IU; lower quartile 2,000, upper quartile 3,000) significantly reduced the INR from 1.7 +/- 0.1 at baseline to 1.4 +/- 0.1 (P < 0.001). This decrease was unrelated to fresh frozen plasma or vitamin K administration. Bleeding stopped after prothrombin complex concentrate administration in 4/11 (36%) patients with surgical bleeding and 26/27 (96%) patients with diffuse bleeding. Hemoglobin levels increased significantly from baseline in bleeding patients (P < 0.05) and mean arterial pressure stabilized (P < 0.05). No thrombotic events or changes in organ function were reported in any patient.

Conclusions: Prothrombin complex concentrate application effectively reduced international normalized ratios in anticoagulation reversal, allowing surgical procedures and interventions without major bleeding. In bleeding patients, the improvement in coagulation after prothrombin complex concentrate administration was judged to be clinically significant.

Figure 1

Dose of prothrombin complex concentrate administered to: (a) surgical patients requiring urgent reversal of vitamin K antagonist therapy, (b) patients with severe bleeding.

Figure 2

International normalized ratios and Quick values (%) before and after infusion of prothrombin complex concentrate in: (a) patients requiring urgent reversal of vitamin K antagonist therapy; and (b) patients with severe bleeding. * P < 0.001 vs before in prothrombin complex concentrate.

Figure 3

Mean ± standard error of the mean international normalized ratios before and after infusion of prothrombin complex concentrate in patients with severe bleeding. (a) Additional FFP treatment did not influence INR, white bars: patients receiving additional fresh frozen plasma (FFP) (n = 11); black bars: patients not receiving additional FFP (n = 27). (b) Administration of more units of FFP did not influence INR, white bars: patients receiving ≥ 6 units additional FFP (n = 4); black bars: patients receiving <6 units additional FFP (n = 7). * P < 0.001 vs pre-PCC.

Figure 4

International normalized ratios before and after infusion of prothrombin complex concentrate in patients with severe bleeding who received additional conservative therapies: the change in INR was unaffected by the addition of (a) FFP, n = 11 and (b) vitamin K, n = 5.

Figure 5

Mean ± standard error of the mean hemoglobin concentrations in patients requiring urgent reversal of vitamin K antagonist therapy (reversal) or with severe bleeding (bleeding). White bars: before (baseline); black bars: after infusion of prothrombin complex concentrate. The mean ± SEM units of red blood cells transfused in each patient group are also shown. Light gray bar: patients requiring urgent reversal of vitamin K antagonist therapy; dark gray bar: patients with severe bleeding. * P < 0.05 vs baseline.

Figure 6

Mean ± standard error of the mean systolic and diastolic arterial blood pressure in patients requiring urgent reversal of vitamin K antagonist therapy (reversal) or with severe bleeding (bleeding). Black bars: systolic blood pressure; gray bars: mean arterial pressure; white bars: diastolic blood pressure. * P < 0.05 vs before prothrombin complex concentrate.

Figure 7

Mean ± standard error of the mean heart rate in patients requiring urgent reversal of vitamin K antagonist therapy (reversal) or with severe bleeding (bleeding). There was a significant increase in systemic blood pressure in bleeding patients after prothrombin complex concentrate application (P < 0.01 vs before PCC). White bars: before (baseline); black bars: after infusion of prothrombin complex concentrate (PCC).