Department of Cardiothoracic and ORL Anaesthesia, Auckland City Hospital, Auckland, New Zealand.
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.
Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post-cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation. OBJECTIVES: Assess the benefits and harms of PCCs in people undergoing cardiac surgery who have coagulopathic non-surgical bleeding.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase and Conference Proceedings Citation Index-Science (CPCI-S) on the Web of Science on 20 April 2021. We searched Clinicaltrials.gov (www.
gov), and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/), for ongoing or unpublished trials. We checked the reference lists for additional references. We did not limit the searches by language or publication status.
We included randomised controlled trials (RCTs) and non-randomised trials (NRSs). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Eighteen studies were included (4993 participants). Two were RCTs (151 participants) and 16 were NRSs. Both RCTs had low risk of bias (RoB) in almost all domains. Of the 16 NRSs, 14 were retrospective cohort analyses with one prospective study and one case report. The nine studies used in quantitative analysis were judged to have critical RoB, three serious and three moderate. 1. PCC versus standard treatment Evidence from RCTs showed PCCs are likely to reduce the number of units transfused compared to standard care (MD -0.89, 95% CI -1.78 to 0.00; participants = 151; studies = 2; moderate-quality evidence). Evidence from NRSs agreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (MD -1.87 units, 95% CI -2.53 to -1.20; participants = 551; studies = 2; very low-quality evidence). There was no evidence from RCTs showing a difference in the incidence of red blood cell (RBC) transfusion compared to standard care (OR 0.53, 95% CI 0.20 to 1.40; participants = 101; studies = 1; low-quality evidence). Evidence from NRSs disagreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (OR 0.54, 95% CI 0.30 to 0.98; participants = 1046; studies = 4; low-quality evidence). There was no evidence from RCTs showing a difference in the number of thrombotic events with PCC compared to standard care (OR 0.68 95% CI 0.20 to 2.31; participants = 152; studies = 2; moderate-quality evidence). This is supported by NRSs, showing that PCCs may have no effect on the number of thrombotic events compared to standard care but the evidence is very uncertain (OR 1.32, 95% CI 0.87 to 1.99; participants = 1359; studies = 7; very low-quality evidence). There was no evidence from RCTs showing a difference in mortality with PCC compared to standard care (OR 0.53, 95% CI 0.12 to 2.35; participants = 149; studies = 2; moderate-quality evidence). This is supported by evidence from NRSs, showing that PCCs may have little to no effect on mortality compared to standard care but the evidence is very uncertain (OR 1.02, 95% CI 0.69 to 1.51; participants = 1334; studies = 6; very low-quality evidence). Evidence from RCTs indicated that there was little to no difference in postoperative bleeding (MD -107.05 mLs, 95% CI -278.92 to 64.83; participants = 151, studies = 2; low-quality evidence). PCCs may have little to no effect on intensive care length of stay (RCT evidence: MD -0.35 hours, 95% CI -19.26 to 18.57; participants = 151; studies = 2; moderate-quality evidence) (NRS evidence: MD -18.00, 95% CI -43.14 to 7.14; participants = 225; studies = 1; very low-quality evidence) or incidence of renal replacement therapy (RCT evidence: OR 0.72, 95% CI 0.14 to 3.59; participants = 50; studies = 1; low-quality evidence) (NRS evidence: OR 1.46, 95% CI 0.71 to 2.98; participants = 684; studies = 2; very low-quality evidence). No studies reported on additional adverse outcomes. 2. PCC versus rFVIIa For this comparison, all evidence was provided from NRSs. PCC likely results in a large reduction of RBCs transfused intra-operatively in comparison to rFVIIa (MD-4.98 units, 95% CI -6.37 to -3.59; participants = 256; studies = 2; moderate-quality evidence). PCC may have little to no effect on the incidence of RBC units transfused comparative to rFVIIa; evidence is very uncertain (OR 0.16, 95% CI 0.02 to 1.56; participants = 150; studies = 1; very low-quality evidence). PCC may have little to no effect on the number of thrombotic events comparative to rFVIIa; evidence is very uncertain (OR 0.51, 95% CI 0.23 to 1.16; participants = 407; studies = 4; very low-quality evidence). PCC may have little to no effect on the incidence of mortality (OR 1.07, 95% CI 0.38 to 3.03; participants = 278; studies = 3; very low-quality evidence) or intensive care length of stay comparative to rFVIIa (MD -40 hours, 95% CI -110.41 to 30.41; participants = 106; studies = 1; very low-quality evidence); evidence is very uncertain . PCC may reduce bleeding (MD -674.34 mLs, 95% CI -906.04 to -442.64; participants = 150; studies = 1; very low-quality evidence) and incidence of renal replacement therapy (OR 0.29, 95% CI 0.12 to 0.71; participants = 106; studies = 1; very low-quality evidence) comparative to rFVIIa; evidence is very uncertain. No studies reported on other adverse events. AUTHORS' CONCLUSIONS: PCCs could potentially be used as an alternative to standard therapy for coagulopathic bleeding post-cardiac surgery compared to FFP as shown by moderate-quality evidence and it may be an alternative to rFVIIa in refractory non-surgical bleeding but this is based on moderate to very low quality of evidence.
心脏手术后的凝血功能障碍与大量输血和高发病率及死亡率密切相关。心脏手术后凝血功能障碍的治疗具有挑战性，基于输血新鲜冰冻血浆（FFP）来替代凝血因子。相比重组因子 VIIa（rFVIIa），凝血酶原复合物浓缩物（PCCs）是一种替代方法来替代凝血因子，值得评估。PCCs 也是治疗心脏手术后难治性持续出血的替代方法，这也需要评估。目的：评估在发生凝血功能障碍性非手术性出血的心脏手术患者中使用 PCCs 的获益和危害。
我们在 Cochrane 图书馆的 Cochrane 对照试验中心注册库（CENTRAL）、MEDLINE、Embase 和 Web of Science 上的科学会议录索引（CPCI-S）上搜索了 2021 年 4 月 20 日的相关研究。我们还在 Clinicaltrials.gov（www.clinicaltrials.gov）和世界卫生组织（WHO）国际临床试验注册平台（ICTRP；apps.who.int/trialsearch/）上搜索了正在进行或未发表的试验。我们检查了参考文献列表以获取其他参考文献。我们没有对语言或发布状态进行任何限制。
我们纳入了随机对照试验（RCTs）和非随机对照试验（NRSs）。
我们使用了 Cochrane 预期的标准方法学程序。
共纳入 18 项研究（4993 名参与者）。其中两项为 RCTs（151 名参与者），16 项为 NRSs。两项 RCTs 在几乎所有领域均具有低偏倚风险（RoB）。16 项 NRS 中，有 14 项为回顾性队列分析，其中 1 项为前瞻性研究，1 项为病例报告。在进行定量分析的 9 项研究中，我们判断其存在严重和中度 RoB。
PCC 与标准治疗：来自 RCTs 的证据表明，与标准护理相比，PCCs 可能会减少输血单位的数量（MD-0.89，95%CI-1.78 至 0.00；参与者=151；研究=2；中等质量证据）。来自 NRSs 的证据也表明，与标准护理相比，PCCs 可能会减少平均输注的单位数量，但证据不确定（MD-1.87 单位，95%CI-2.53 至-1.20；参与者=551；研究=2；极低质量证据）。来自 RCTs 的证据表明，与标准护理相比，PCCs 对红细胞（RBC）输注的发生率没有差异（OR 0.53，95%CI 0.20 至 1.40；参与者=101；研究=1；低质量证据）。来自 NRSs 的证据不同意这一观点，表明与标准护理相比，PCCs 可能会减少平均输注的单位数量，但证据不确定（OR 0.54，95%CI 0.30 至 0.98；参与者=1046；研究=4；低质量证据）。来自 RCTs 的证据表明，与标准护理相比，PCCs 在血栓事件的发生率方面没有差异（OR 0.68，95%CI 0.20 至 2.31；参与者=152；研究=2；中等质量证据）。这一结果得到了 NRSs 的支持，表明与标准护理相比，PCCs 对血栓事件的发生率可能没有影响，但证据非常不确定（OR 1.32，95%CI 0.87 至 1.99；参与者=1359；研究=7；极低质量证据）。来自 RCTs 的证据表明，与标准护理相比，PCCs 在死亡率方面没有差异（OR 0.53，95%CI 0.12 至 2.35；参与者=149；研究=2；中等质量证据）。这一结果也得到了 NRSs 的支持，表明与标准护理相比，PCCs 对死亡率的影响可能很小或没有，但证据非常不确定（OR 1.02，95%CI 0.69 至 1.51；参与者=1334；研究=6；极低质量证据）。RCT 证据表明，PCCs 在术后出血方面可能没有差异（MD-107.05 mLs，95%CI-278.92 至 64.83；参与者=151，研究=2；低质量证据）。PCCs 对重症监护时间的长短可能没有影响（RCT 证据：MD-0.35 小时，95%CI-19.26 至 18.57；参与者=151；研究=2；中等质量证据）（NRS 证据：MD-18.00，95%CI-43.14 至 7.14；参与者=225；研究=1；极低质量证据）或肾脏替代治疗的发生率（RCT 证据：OR 0.72，95%CI 0.14 至 3.59；参与者=50；研究=1；低质量证据）（NRS 证据：OR 1.46，95%CI 0.71 至 2.98；参与者=684；研究=2；极低质量证据）。没有研究报告其他不良结局。
PCC 与 rFVIIa：对于这一比较，所有证据均来自 NRSs。与 rFVIIa 相比，PCCs 可能会大量减少术中输注的 RBCs（MD-4.98 单位，95%CI-6.37 至-3.59；参与者=256；研究=2；中等质量证据）。与 rFVIIa 相比，PCCs 对 RBC 单位输注的发生率可能没有影响，证据不确定（OR 0.16，95%CI 0.02 至 1.56；参与者=150；研究=1；极低质量证据）。与 rFVIIa 相比，PCCs 对血栓事件的发生率可能没有影响，证据不确定（OR 0.51，95%CI 0.23 至 1.16；参与者=407；研究=4；极低质量证据）。与 rFVIIa 相比，PCCs 对死亡率（OR 1.07，95%CI 0.38 至 3.03；参与者=278；研究=3；极低质量证据）或重症监护时间的长短（MD-40 小时，95%CI-110.41 至 30.41；参与者=106；研究=1；极低质量证据）可能没有影响，证据不确定。PCCs 可能会减少出血（MD-674.34 mLs，95%CI-906.04 至-442.64；参与者=150；研究=1；极低质量证据）和肾脏替代治疗的发生率（OR 0.29，95%CI 0.12 至 0.71；参与者=106；研究=1；极低质量证据），与 rFVIIa 相比，证据不确定。没有研究报告其他不良事件。
与 FFP 相比，PCCs 可能是心脏手术后凝血功能障碍性出血的替代治疗方法，证据质量为中等，与 rFVIIa 相比，PCCs 可能是难治性非手术性出血的替代治疗方法，但这基于中等至极低质量的证据。
