加拿大多伦多总医院Keyvan Karkouti研究团队，近日研究比较了纤维蛋白原浓缩物与冷沉淀对心脏手术后输血的影响。这一研究成果10月21日在线发表于《美国医学会杂志》。

大出血是心脏手术的常见并发症。获得性低纤维蛋白原血症（纤维蛋白原水平<1.5-2.0 g/L）是出血的重要原因，为此，指南建议采用冷沉淀或纤维蛋白原浓缩物来替代纤维蛋白原。这两种产品差异较大，但缺乏临床对比数据。

2017年2月10日至2018年11月1日，研究组在加拿大的11家医院进行了一项随机临床试验，招募心脏手术后出现临床大出血和低纤维蛋白原血症的成年患者，并随访至2018年11月28日。最终有735例患者接受治疗并完成试验，中位年龄为64岁，72%接受复杂手术，95%伴有中重度出血。将其随机分组，在体外循环术后24小时内，372例接受纤维蛋白原浓缩物治疗，363例接受冷沉淀治疗。

该试验进行到中期便达到了非劣效性停止标准。纤维蛋白原浓缩物组平均24小时同种异体输血量为16.3单位，冷沉淀组为17.0单位，差异不显著。纤维蛋白原浓缩物组发生血栓栓塞事件26例（7.0%），冷沉淀组发生35例（9.6%）。

总之，对于接受心脏手术在体外循环术后出现临床意义上的出血和低纤维蛋白原血症的患者，纤维蛋白原浓缩物与冷沉淀治疗相比，术后24小时内输注的血液成分数量方面疗效相当。

附：英文原文

Title: Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery The FIBRES Randomized Clinical Trial

Author: Jeannie Callum, Michael E. Farkouh, Damon C. Scales, Nancy M. Heddle, Mark Crowther, Vivek Rao, Hans-Peter Hucke, Jo Carroll, Deep Grewal, Sukhpal Brar, Jean Bussières, Hilary Grocott, Christopher Harle, Katerina Pavenski, Antoine Rochon, Tarit Saha, Lois Shepherd, Summer Syed, Diem Tran, Daniel Wong, Michelle Zeller, Keyvan Karkouti

Issue&Volume: 2019/10/21

Abstract: 

Importance  Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate or fibrinogen concentrate. The 2 products have important differences, but comparative clinical data are lacking.

Objective  To determine if fibrinogen concentrate is noninferior to cryoprecipitate for treatment of bleeding related to hypofibrinogenemia after cardiac surgery.

Design, Setting, and Participants  Randomized clinical trial at 11 Canadian hospitals enrolling adult patients experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery (from February 10, 2017, to November 1, 2018). Final 28-day follow-up visit was completed on November 28, 2018.

Interventions  Fibrinogen concentrate (4 g; n = 415) or cryoprecipitate (10 units; n = 412) for each ordered dose within 24 hours after cardiopulmonary bypass.

Main Outcomes and Measures  Primary outcome was blood components (red blood cells, platelets, plasma) administered during 24 hours post bypass. A 2-sample, 1-sided test for the ratio of the mean number of units was conducted to evaluate noninferiority (threshold for noninferiority ratio, <1.2).

Results  Of 827 randomized patients, 735 (372 fibrinogen concentrate, 363 cryoprecipitate) were treated and included in the primary analysis (median age, 64 [interquartile range, 53-72] years; 30% women; 72% underwent complex operations; 95% moderate to severe bleeding; and pretreatment fibrinogen level, 1.6 [interquartile range, 1.3-1.9] g/L). The trial met the a priori stopping criterion for noninferiority at the interim analysis after 827 of planned 1200 patients were randomized. Mean 24-hour postbypass allogeneic transfusions were 16.3 (95% CI, 14.9 to 17.8) units in the fibrinogen concentrate group and 17.0 (95% CI, 15.6 to 18.6) units in the cryoprecipitate group (ratio, 0.96 [1-sided 97.5% CI, −∞ to 1.09; P < .001 for noninferiority] [2-sided 95% CI, 0.84 to 1.09; P = .50 for superiority]). Thromboembolic events occurred in 26 patients (7.0%) in the fibrinogen concentrate group and 35 patients (9.6%) in the cryoprecipitate group.

Conclusions and Relevance  In patients undergoing cardiac surgery who develop clinically significant bleeding and hypofibrinogenemia after cardiopulmonary bypass, fibrinogen concentrate is noninferior to cryoprecipitate with regard to number of blood components transfused in a 24-hour period post bypass. Use of fibrinogen concentrate may be considered for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery.

DOI: 10.1001/jama.2019.17312

Source: https://jamanetwork.com/journals/jama/fullarticle/2753529