Intraoperative Use of Low-Dose Recombinant Activated Factor VII During Thoracic Aortic Operations

Abstract

Background Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Methods Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Results Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16–43 μg/kg) rFVIIa given 51 minutes (42–67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p = 0.05; international normalized ratio, 0.8 versus 1.2; p < 0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p = 0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Conclusions Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach.

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

“…The use of rFVIIa in high-risk cardiac surgical cases with refractory hemorrhage has been described in retrospective studies. 21,64,65 Identified predictors of treatment failure included baseline INR > 2.0, platelet count < 80 × 10 9 /L, fibrinogen levels < 100 mg/dL, and more than 15 units of packed red blood cell transfused prior to administration of rFVIIa. 21 High thromboembolism rate (> 20%), 22 a complication rate of 44%, 21 and a mortality of 32% 21 were also described.…”

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

“…Reduced bleeding is observed in propensity-matched studies when patients undergoing cardiac surgery receive low-dose rFVIIa compared with placebo. 64,67 Intuitively, fewer adverse thromboembolic effects would be expected with lower doses of rFVIIa, and the higher doses (70-90 μg/kg) used for bypassing activity in hemophiliacs are unnecessary in the nonhemophiliac surgical patient because the intrinsic Xase enzyme complex is intact. Failure to address platelet; fibrinogen; and factors II, VIII, IX, or X deficiencies in patients with severe hemorrhage will limit the effectiveness of rFVIIa to restore thrombin generation and fibrin clot formation (Fig.…”

“…The use of rFVIIa in high-risk cardiac surgical cases with refractory hemorrhage has been described in retrospective studies. 21,64,65 Identified predictors of treatment failure included baseline INR >2.0, platelet count <80 × 10 9 /L, fibrinogen levels <100 mg/dL, and >15 units of packed red blood cells transfused before administration of rFVIIa. 21 High thromboembolism rate (>20%), 22 a complication rate of 44%, 21 and a mortality of 32% 21 were also described.…”

The utility of the aortic dissection team: outcomes and insights after a decade of experience

“…Adjunctive antegrade cerebral perfusion via the right axillary artery is the preferred cerebral protection strategy in circulatory arrest cases, with retrograde cerebral perfusion being utilized in cases where the right axillary artery is not suitable for cannulation as previously described (26). Transfusion practices are performed as previously described, with intraoperative low-dose recombinant activated factor VII (rFVIIa) and/or prothrombin complex concentrate administered to patients with severe coagulopathy refractory to routine transfusions (26,31,32). Distal arch procedures or attempts to obliterate the descending thoracic aortic false lumen (i.e., frozen elephant trunk procedures) are not routinely performed, but rather, used selectively, such as in the case of a distal arch primary tear (retrograde type A dissection) or markedly …”