A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding With Cardiac Surgery

Abstract

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

Alternative Factor Prescribing after Low-Dose Recombinant Factor VIIa Protocol in Cardiac Surgery

“…More recently, we have learned low-doses of 4-factor PCC may be sufficient; a 2021 study found low-dose rFVIIa (2 mg or 20 mcg/kg) and low-dose 4-factor PCC (1000 units or 15 units/kg) were equally safe and effective for refractory bleeding in cardiac surgery. 32 In the absence of a 4-factor PCC dosing protocol, there is potential for administration of larger than necessary doses (e.g., 2,172 units/patient pre-protocol and 4,284 units/patient post-protocol in our 15 study). Therefore, if restricting rFVIIa off-label use, it seems critical to also standardize use and dosing of both PCC and rFVIIa to avoid shifts in prescribing or overutilization of PCC.…”

Dosing, Monitoring, Blood Product Utilization, and Thromboembolic Complications of Four-Factor Prothrombin Complex Concentrate as Part of an Institutional Protocol in Pediatric Cardiac Surgery: A Retrospective Cohort Study

“…While the design of this study did not compare patients who received 4F-PCC to those who did not, the reported chest tube output and blood product transfusion in the postoperative setting are less than those reported in other pediatric cardiac surgery studies. 21 22 23 24 25 27 28 29 30 31…”

“…While the design of this study did not compare patients who received 4F-PCC to those who did not, the reported chest tube output and blood product transfusion in the postoperative setting are less than those reported in other pediatric cardiac surgery studies. [21][22][23][24][25][27][28][29][30][31] Bleeding is a common issue in pediatric patients undergoing cardiac surgery requiring CPB, and the lack of standard guidelines often results in utilization of a wide variety of blood products. Mechanisms contributing to excessive bleeding following CPB include heparinization, hemodilution through circuit prime, hypothermia, as well as interactions between the coagulation and inflammatory systems.…”

Resolution of cardiac surgical bleeding with the combination of 4-factor prothrombin complex concentrate and fresh frozen plasma following lack of response to fresh frozen plasma alone in a patient with severe factor XI deficiency

“…Thrombosis rates were higher in the recombinant factor VIIa versus the 4-factor PCC groups, but the differences were not statistically significant (10 vs. 3.6%, P ¼ 0.159; 26 vs. 13%, P ¼ 0.08.) [14,15] 4-factor PCC is less expensive. The cost of 4-factor PCC is $ 3.41 per unit, whereas the cost of recombinant factor VIIa is $2.98/mg [16].…”