Montonye, Beth L.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

Introduction: Post-Cardiopulmonary Bypass (CPB) coagulopathy results in bleeding, transfusion and re-exploration, and increases morbidity, mortality and cost. Some studies have reported a relationship between individual factor levels and chest tube drainage as a marker of bleeding, but few have reported that relationship for multiple factors. Methods: With IRB approval and informed consent, 98 patients, ages 18 - 85, undergoing cardiac surgery with cardiopulmonary bypass (CPB) were studied. Factor levels measured five minutes post-protamine included fibrinogen (FIB), and factors II, V, VII, VIII, Von Willebrand Factor Antigen (VWF Ag), Ristocetin Cofactor (VWF Activity), IX, X, XI and XIII. Linear regression models examined the relationship between factor levels and post-op chest tube drainage over 24 hours as a surrogate marker for bleeding. An effect size (ES) was calculated so that each factor deficiency multiplied by the ES and the patient's weight in kg would estimate the contribution of that factor to bleeding. Factors were ranked from most to least impact on bleeding. Conversely, said ES would estimate the decrease in bleeding achieved by a percentage increase in a deficient factor level if such factor was known to be deficient. Results: F:II was 1st (most associated with bleeding), ES = -0.137, 95% CI -0.214 - -0.059, p < 0.001; F:X was 2nd, ES = -0.130, 95% CI -0.202 - -0.058, p < 0.001; F:VII ES = -0.121, 95% CI -0.198 - -0.045, p = 0.002; F:XI ES = -0.109, 95% CI -0.16 - -0.058, p < 0.001; F:IX ES = -0.100; 95% CI -0.135 - -0.065, p < 0.001; F:V ES = - 0.065; 95% CI -0.114 - -0.016, p = 0.011; F:XIII ES = - 0.055; 95% CI -0.099 - -0.011, p = 0.016; FIB ES = - 0.042; 95% CI -0.063 - -0.022, p < 0.001; F:VIII ES = - 0.007; 95% CI -0.020 - 0.006, p = 0.318; VWF Ag ES = 0.002; 95% CI -0.016 - 0.019, p = 0.855; VWF Activity ES = 0.004; 95% CI -0.015 - 0.023, p = 0.671. Conclusions: Factors VIII, VWF Ag and Ristocetin Cofactor demonstrated no relationship with bleeding, perhaps because they are elevated as acute-phase reactants. In theory, raising F:II level post-CPB by 30% in an 80 kg patient might decrease bleeding by 328 ml, and raising F:X level post-CPB by 30% in an 80 kg patient might decrease bleeding by 312 ml, etc. A weakness of this study is that the sample size was too small to perform a multi-variate analysis considering all factor levels. Still, the data suggest four-factor prothrombin complex concentrate (PCC) might be a more effective treatment for post-CPB coagulopathy than FFP. The data do not confirm cause and effect; that would require a large study with control and treatment arms. If multiple factor levels could be measured in a rapid and cost-effective manner it might aid in targeted treatment of post-CPB coagulopathy. The data suggest that work should be performed to better elucidate the contribution of coagulation factor deficiencies to post-CPB bleeding, as improved treatment of such factor deficiencies might decrease bleeding and transfusion requirements.