Out of Control: Why Randomized Trials of Factor Concentrates Are So Elusive

Abstract

Bleeding in the perioperative and postoperative periods continues to be a major concern in cardiac surgery. 1 Although, in most cases, the combination of blood product transfusion, antifibrinolytic therapy, improved surgical hemostasis, and time are sufficient to achieve hemostasis, this is not always adequate. The reasons for variability in perioperative hemostasis are not known, although certain patient and surgical characteristics, including prior history of cardiac surgery, underlying bleeding diathesis, emergent surgery, and cardiopulmonary bypass (CPB) duration, have been associated with increased peri-and postoperative bleeding. 1,2 Despite often uncertain causes of persistent perioperative bleeding, even with usual resuscitative efforts, practitioners frequently turn to purified coagulation factor concentrates to enhance hemostasis. These include three-or four-factor prothrombin complex concentrates (3F-PCC or 4F-PCC), 3,4 recombinant activated factor VII (rVIIa) (NovoSeven), 4,5 and, as described by O'Donnell et al. in this issue of the Journal of Cardiothoracic and Vascular Anesthesia, activated prothrombin complex concentrates, 6 also known as factor 8 inhibitor bypassing agent (FEIBA). Although 4F-PCC sometimes is used in cardiac surgery for its approved indication of warfarin reversal, the use of purified factor concentrates is, in general, off-label, in large part due to the lack of data supporting their efficacy and safety in this patient population.

Coagulation and Transfusion Updates From 2021

“…Continued research with larger randomized studies, although challenging, still is needed in this patient population to further determine efficacy and safety. 32 Despite the above data suggesting no significant thrombotic complications with PCC, there remains hesitancy in utilizing PCC for coagulopathy during use of mechanical circulatory support. This past year has provided some additional insight into the use of PCC for left ventricular assist device (LVAD) implantation or exchange.…”