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Evaluation of combined idarucizumab and prothrombin complex concentrate treatment for bleeding related to dabigatran in a lethal porcine model of double trauma
Author(s) -
Honickel Markus,
Braunschweig Till,
Rossaint Rolf,
Schöchl Herbert,
Grottke Oliver
Publication year - 2019
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.15117
Subject(s) - dabigatran , medicine , idarucizumab , prothrombin complex concentrate , antidote , anesthesia , direct thrombin inhibitor , placebo , prothrombin time , surgery , anticoagulant , warfarin , alternative medicine , toxicity , pathology , atrial fibrillation
BACKGROUND Idarucizumab (IDA) is approved for emergency reversal of dabigatran; prothrombin complex concentrates (PCCs) are recommended in the absence of specific antidote. The combined effects of IDA and PCC in trauma‐related bleeding are unknown. The efficacy and safety of combined IDA + PCC were assessed in a lethal porcine model of double trauma under dabigatran anticoagulation. STUDY DESIGN AND METHODS Male pigs (n = 28) received oral dabigatran etexilate (30 mg/kg bid) for 3 days; a non‐dabigatran control group (n = 7) received placebo. On Day 4, dabigatran‐treated animals were randomized 1:1:1:1 to receive placebo + placebo (dabigatran‐treated control), IDA + PCC (60 mg/kg + 50 IU/kg), PCC + IDA, or IDA + IDA. Trauma was induced at t = 0 (bilateral femur fractures and blunt liver injury) and t = 60 minutes (second blunt liver injury). Study treatment was administered 15 minutes after each trauma. Animals were monitored for 5 hours or until death. RESULTS Total blood loss in IDA + PCC, PCC + IDA, and IDA + IDA was 1673 ± 370, 1981 ± 361, and 1417 ± 135 mL, respectively, with 100% survival at 5 hours. Blood loss in dabigatran‐treated controls was 4427 ± 162 mL with 100% mortality. With IDA + IDA, plasma coagulation parameters and thrombin generation were similar to non‐dabigatran control group levels after the second dose and remained stable over time. In the IDA + PCC and PCC + IDA groups, thrombin generation and d ‐dimer levels after the second dose were higher than with IDA + IDA. No thromboembolic complications were found. CONCLUSION IDA and PCC are effective in treating trauma‐related bleeding with dabigatran anticoagulation. IDA is preferable for emergency reversal of dabigatran, but PCC may be valuable when the anticoagulant is unknown.