法国格勒诺布尔阿尔卑斯大学Pierre Bouzat团队研究了4因子凝血酶原复合物对有大量输血风险的创伤患者的疗效和安全性。2023年3月21日出版的《美国医学会杂志》发表了这项成果。

外伤性出血的最佳输血策略尚不清楚。报告显示，4因子凝血酶原复合物浓缩物（4F-PCC）对血液制品消耗临床有益。

为了探讨4F-PCC给药治疗有大量输血风险患者的有效性和安全性，2017年12月29日至2021年8月31日，研究组在法国12个指定的一级创伤中心进行了双盲、随机、安慰剂对照的优势试验，涉及连续的创伤患者，这些患者有大量输血的风险。随访于2021年8月31日完成。

干预措施为静脉给药1 mL/kg 4F-PCC（25 IU因子IX/kg）或1 mL/kg生理盐水（安慰剂）。患者、研究人员和数据分析人员对治疗分配双盲。所有患者都接受了基于比例的早期输血（填充红细胞：新鲜冷冻血浆比例为1:1至2:1），并根据欧洲创伤出血指南进行治疗。主要结局是24小时内所有血液制品的消耗（疗效）；动脉或静脉血栓栓塞事件是次要结局（安全性）。

在4313名创伤激活程度最高的患者中，350人有资格紧急纳入，327人被随机分组，324人被分析（4F-PCC组164人，安慰剂组160人）。参与者的中位（IQR）年龄为39岁（27-56岁），损伤严重程度评分为36分（26-50分[重大创伤]），入院血液乳酸水平为4.6（2.8-7.4）mmol/L；324名患者中有179名（59%）院前动脉收缩压低于90毫米汞柱，233名（73%）患者为男性，226名（69%）患者需及时控制出血。

24小时血液制品总消耗中位数组间无统计学或临床显著差异（4F-PCC组12U，安慰剂组11U；绝对差异为0.2U）。在4F-PCC组中，56名患者（35%）出现至少1次血栓栓塞事件，而安慰剂组有37名患者（24%）（绝对差异为11%；相对风险为1.48，组间差异显著）。

研究结果表明，对于有大量输血风险的创伤患者，4F-PCC给药后24小时血液制品消耗没有显著减少，但血栓栓塞事件更常见。这些发现不支持在有大量输血风险的患者中系统使用4F-PCC。

附：英文原文

Title: Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial

Author: Pierre Bouzat, Jonathan Charbit, Paer-Selim Abback, Delphine Huet-Garrigue, Nathalie Delhaye, Marc Leone, Guillaume Marcotte, Jean-Stéphane David, Albrice Levrat, Karim Asehnoune, Julien Pottecher, Jacques Duranteau, Elie Courvalin, Anais Adolle, Dimitri Sourd, Jean-Luc Bosson, Bruno Riou, Tobias Gauss, Jean-Franois Payen, PROCOAG Study Group, Jules Greze, Pierluigi Banco, Karine Berger, Stéphanie Druge, Martin Dupuis, Laure Janin, Caroline Machuron, Marine Thomas, Clotilde Schilte, Emmanuelle Hamad, Laurent Zieleskiewicz, Gary Duclos, Charlotte Arbelot, Karine Bezulier, Caroline Jeantrelle, Mathieu Raux, Pauline Glasman, Anatole Harrois, Virginie Tarazona, Aline Lambert, Olivia Vassal, Anne Li, Nicolas Grillot, Los Henry, Elise Blonde, Benjamin Bijok, Aurélien Rohn, Julie Bellet, Florence Lallemant, Nathalie Bruneau, Christine Ducam, Geoffrey Dagod, Pauline Deras, Xavier Capdevila, Magdalena Szczot, Alain Meyer, Stéphane Hecketsweiler, Etienne Escudier, Michel Muller, Samuel Gray, Magalie Farines, Marie Lebouc, Sophie DEBORD-PEDET

Issue&Volume: 2023-03-21

Abstract:

Importance  Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.

Objective  To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion.

Design, Setting, and Participants  Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021.

Interventions  Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.

Main Outcomes and Measures  The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety).

Results  Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, 2.99 to 3.33]; P=.72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P=.03).

Conclusions and Relevance  Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion.

DOI: 10.1001/jama.2023.4080

Source: https://jamanetwork.com/journals/jama/fullarticle/2802855