Prothrombin complex concentrate (Beriplex® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial

Abstract

SummaryBackground: Prothrombin complex concentrate (PCC) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy (OAT). Objectives. To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC (Beriplex® P/N) containing coagulation factors II, VII, IX, and X, and anticoagulant proteins C and S. Patients and methods: Patients receiving OAT were eligible for this prospective multinational study if their International Normalized Ratio (INR) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding. Stratified 25, 35, or 50 IU kg−1 PCC doses were infused based on initial INR. Study endpoints included INR normalization (≤1.3) by 30 min after PCC infusion and hemostatic efficacy. Results: Forty‐three patients, 26 requiring interventional procedures and 17 experiencing acute bleeding, received PCC infusions at a median rate of 7.5 mL min−1 (188 IU min−1). At 30 min thereafter, INR declined to ≤1.3 in 93% of patients. At all postinfusion time points through 48 h, median INR remained between 1.2 and 1.3. Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients (98%). Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed. One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCC‐related. Conclusions: PCC treatment serves as an effective rapid hemorrhage control resource in the emergency anticoagulant reversal setting. More widespread availability of PCC is warranted to ensure its benefits in appropriate patients. Background: Prothrombin complex concentrate (PCC) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy (OAT). Objectives. To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC (Beriplex® P/N) containing coagulation factors II, VII, IX, and X, and anticoagulant proteins C and S. Patients and methods: Patients receiving OAT were eligible for this prospective multinational study if their International Normalized Ratio (INR) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding. Stratified 25, 35, or 50 IU kg−1 PCC doses were infused based on initial INR. Study endpoints included INR normalization (≤1.3) by 30 min after PCC infusion and hemostatic efficacy. Results: Forty‐three patients, 26 requiring interventional procedures and 17 experiencing acute bleeding, received PCC infusions at a median rate of 7.5 mL min−1 (188 IU min−1). At 30 min thereafter, INR declined to ≤1.3 in 93% of patients. At all postinfusion time points through 48 h, median INR remained between 1.2 and 1.3. Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients (98%). Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed. One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCC‐related. Conclusions: PCC treatment serves as an effective rapid hemorrhage control resource in the emergency anticoagulant reversal setting. More widespread availability of PCC is warranted to ensure its benefits in appropriate patients.