Welsby Ian J, Schroeder Darrell R, Ghadimi Kamrouz, Nuttall Gregory A, Smith Mark M
Department of Anesthesiology & Critical Care, Duke University Medical Center, Erwin Road, Durham, NC, 27710, USA.
Department of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
J Thromb Thrombolysis. 2025 Feb;58(2):309-318. doi: 10.1007/s11239-024-03061-3. Epub 2024 Dec 4.
Thrombin generation (TG) is reduced after cardiac surgery using cardiopulmonary bypass (CPB), contributing to coagulopathy and bleeding. Plasma transfusion or four-factor prothrombin complex concentrate (PCC) are commonly used to treat coagulopathic bleeding after CPB without knowledge of how each may restore TG. To determine the effect of PCC infusion on restoration of thrombin generation compared with plasma transfusion, we performed a laboratory-based secondary analysis of a randomized, controlled trial of adult patients undergoing cardiac surgery to assess efficacy and safety of 4 F-PCC versus plasma for treatment of perioperative coagulopathic bleeding after CPB. Participants were randomized to receive either PCC (15 IU/kg) or plasma (10-15 ml/kg) after separation from CPB. Participant blood samples were obtained at pre-specified serial timepoints, with laboratory assays for TG and factor levels subsequently performed. The primary outcome was change in thrombin generation (TG) parameters after each randomized treatment through postoperative day 5. Secondary outcomes included serially derived clotting factor levels. Of 100 randomized participants, 99 were included in this laboratory analysis (PCC group, N = 51; plasma group, N = 48). After treatment, participants in the PCC group compared with those in the plasma group showed higher endogenous thrombin potential (ETP, Median, Interquartile range, IQR: 688 [371-1069] vs. 1088 [550-1691] nM minutes, P = 0.01), a greater increase din ETP (P = 0.002) and peak TG (P = 0.01) in the timepoints between heparin reversal and after treatment administration. Both groups demonstrated similar values in all TG assays by postoperative day 1 (P > 0.05). The PCC group also demonstrated higher levels of proteins C, S, and Factors II, VII, IX and X, early after treatment (P < 0.001 for all comparisons). Antithrombin levels were initially higher in the plasma group after treatment (Median, IQR: 66% [61-71%] vs. 56% [51-65%], P = 0.002) but differences did not persist beyond postoperative day 3. In this laboratory analysis from a recent randomized trial in adult cardiac surgery, PCC administration restored thrombin generation more rapidly than plasma in the early postoperative period without laboratory evidence of hypercoagulability. ClinicalTrials.gov identifier: NCT02557672 [1].
使用体外循环（CPB）进行心脏手术后，凝血酶生成（TG）减少，这会导致凝血病和出血。血浆输注或四因子凝血酶原复合物浓缩剂（PCC）常用于治疗CPB后的凝血病性出血，但人们并不清楚它们各自如何恢复TG。为了确定与血浆输注相比，PCC输注对凝血酶生成恢复的影响，我们对一项针对接受心脏手术的成年患者的随机对照试验进行了基于实验室的二次分析，以评估4F - PCC与血浆治疗CPB后围手术期凝血病性出血的疗效和安全性。参与者在脱离CPB后被随机分配接受PCC（15 IU/kg）或血浆（10 - 15 ml/kg）。在预先指定的连续时间点采集参与者的血样，随后进行TG和因子水平的实验室检测。主要结局是每种随机治疗后至术后第5天凝血酶生成（TG）参数的变化。次要结局包括连续检测的凝血因子水平。在100名随机参与者中，99名被纳入该实验室分析（PCC组，N = 51；血浆组，N = 48）。治疗后，与血浆组相比，PCC组参与者的内源性凝血酶潜力（ETP，中位数，四分位间距，IQR：688 [371 - 1069] vs. 1088 [550 - 1691] nM分钟，P = 0.01）更高，在肝素逆转至治疗给药后的时间点，ETP（P = 0.002）和TG峰值（P = 0.01）的增加幅度更大。到术后第1天，两组在所有TG检测中的值均相似（P > 0.05）。PCC组在治疗后早期还显示出蛋白C、S以及因子II、VII、IX和X的水平更高（所有比较P < 0.001）。治疗后血浆组的抗凝血酶水平最初较高（中位数，IQR：66% [61 - 71%] vs. 56% [51 - 65%]，P = 0.002），但差异在术后第3天之后不再持续。在这项对近期成年心脏手术随机试验的实验室分析中，PCC给药在术后早期比血浆更迅速地恢复了凝血酶生成，且没有实验室证据表明存在高凝状态。ClinicalTrials.gov标识符：NCT02557672 [1]
