The association of prothrombin complex concentrates with postoperative outcomes in cardiac surgery: an observational substudy of the FIBRES randomized controlled trial

Abstract

Purpose The mainstay of therapy for coagulation factor deficiency in cardiac surgical patients is frozen plasma (FP); however, prothrombin complex concentrates (PCCs) may offer logistical and safety advantages. As there is limited comparative evidence, we conducted this study to explore the association of comparable PCC or FP doses with transfusion and outcomes. Methods This was a post hoc analysis of a multicentre randomized trial comparing fibrinogen concentrate with cryoprecipitate (FIBRES trial) in bleeding cardiac surgical patients. This analysis included 415 patients who received only PCC (n = 72; 17%) or only FP (n = 343; 83%) for factor replacement. The main outcomes of interest were red blood cell (RBC) and platelet transfusion within 24 hr of cardiopulmonary bypass. Secondary outcomes included postoperative adverse events. Associations were examined by hierarchical generalized estimating equation models adjusted for demographic and surgical characteristics. ResultsThe median [interquartile range (IQR)] PCC dose was 1,000 [1,000-2,000] units, while the median [IQR] FP dose was 4 [2-6] units. Each unit of FP was independently associated with increased adjusted odds of RBC (1.60; 95% confidence interval [CI], 1.36 to 1.87; P\0.01) and platelet transfusion (1.40; 95% CI, 1.15 to 1.69; P\0.01) while each 500 units of PCC was independently associated with reduced adjusted odds of RBC (0.67; 95% CI, 0.50 to 0.90; P\0.01) and platelet transfusion (0.80; 95% CI, 0.70 to 0.92; P \ 0.01). Adverse event rates were comparable.

Targeting Chemoprophylaxis in Venous Thromboembolism Using Biomarker Guidance

“…2 Past work has demonstrated pronounced increases in systemic thrombin generation after major trauma, which continues to increase during the initial hours and days after injury, making many patients profoundly hypercoagulable. 3,4 This, combined with ongoing antithrombin inhibition through thrombin-mediated consumption or neutrophil elastase release, as observed in this study, could explain why higher antithrombin levels are linked with VTE in this population (and even higher levels may be required to prevent these events).…”

“…Use of a fixed-dose approach to VTE chemoprophylaxis was criticized over a decade ago when the landmark PROTECT II trial, powered for superiority, surprisingly demonstrated similar rates of VTE development in critically ill patients receiving dalteparin vs unfractionated heparin. 3,4 Underdosing is seen in Vincent et al 1 because neither cohort consistently demonstrated therapeutic anti-Factor Xa (FXa) levels and that it took a significantly longer duration to achieve therapeutic levels in the VTE group. Although antithrombin supplementation can improve the response to heparin in the setting of lower anti-FXa levels, 5 lower anti-FXa levels could be avoided by providing adequate weight-based dosing.…”

“…Our group has advocated for directly measuring a relevant biological end point of VTE chemoprophylaxis vis-à-vis thrombin generation. 3 While thrombin generation assays remain unavailable in the clinical setting, it could be helpful for diagnosis and treatment to measure the time to peak thrombin and endogenous…”

Coagulation and Transfusion Updates From 2021

“…9 An additional observational investigation in postcardiac surgery bleeding compared 415 patients who received either PCC only (n = 72) or FFP only (n = 343). 31 The primary outcome assessment included RBC and platelet transfusion needs in the first 24 hours after bypass. The analysis demonstrated that each unit of FFP was associated with an increase in odds of RBC and platelet transfusion; whereas every 500 units of PCC were associated with a decrease in the odds of RBC and platelet transfusion.…”

Editorial: cardiovascular anaesthesiology

“…Next, Santana et al [22] review the use of PCC in cardiac surgery. They present mechanistic background information, followed by a review of retrospective studies and the handful of prospective clinical trials that demonstrate decreased red blood cell transfusion and more rapid haemostatic correction compared to fresh frozen plasma [23,24]. However, there are currently no data to adequately determine if their use impacts other clinically meaningful outcomes.…”