Prothrombin Complex Concentrate-induced Disseminated Intravascular Coagulation Can Be Prevented by Coadministering Antithrombin in a Porcine Trauma Model

WHAT WE ALREADY KNOW ABOUT THIS TOPICProthrombin complex concentrates are increasingly used as part of bleeding management algorithms in surgery and traumaThere are potential risks of thromboembolic complications and disseminated intravascular coagulopathy with prothrombin complex concentrate in this setting, despite the low risks in warfarin reversal WHAT THIS ARTICLE TELLS US THAT IS NEWIn this animal polytrauma model, 50 IU/kg prothrombin complex concentrate is associated with a risk of disseminated intravascular coagulopathy and thromboembolismThe addition of antithrombin appears to balance the procoagulant effects of prothrombin complex concentrate, consequently reducing the risk of complications without impairing efficacy BACKGROUND:The risk of thromboembolic complications with prothrombin complex concentrates (PCCs) appears low when used for reversal of vitamin K antagonists but might be different in other indications (e.g., trauma). A difference in risk could arise from the plasma ratio of pro- versus anticoagulant proteins. This study used a porcine trauma model to investigate combined treatment with PCC and antithrombin. The hypothesis was that antithrombin can modulate prothrombotic effects and prevent adverse events of PCC. METHODS:Nine treatment groups (n = 7 per group) were includedcontrol (placebo), PCC (50 IU/kg), PCC plus antithrombin (three groups, with antithrombin doses of 12.5, 25, or 50 IU/kg), fibrinogen concentrate (100 mg/kg) plus PCC, fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg, tranexamic acid (15 mg/kg) plus fibrinogen concentrate plus PCC, and tranexamic acid plus fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. In each group, bilateral femur fractures and thorax contusion were followed 60 min later by blunt liver injury. Study treatment was then administered, and animals were subsequently observed for 210 min. RESULTS:Total blood loss (mean ± SD) was statistically significantly lower in all three PCC plus antithrombin groups (PCC plus antithrombin dose of 50 IU/kg, 672 ± 63 ml; PCC plus antithrombin dose of 25 IU/kg, 535 ± 72 ml; and PCC plus antithrombin dose of 12.5 IU/kg, 538 ± 50 ml) than in the PCC group (907 ± 132 ml), which in turn had statistically significantly reduced bleeding versus the control group (1,671 ± 409 ml). Signs of disseminated intravascular coagulation were apparent with PCC monotherapy, and early deaths occurred with fibrinogen concentrate plus PCC, attributabl