Klingele Matthias, Enkel Julia, Speer Timo, Bomberg Hagen, Baerens Lea, Schäfers Hans-Joachim
Department of Internal Medicine, Nephrology and Hypertension, Saarland University Medical Centre, Homburg, Saar, Germany.
Department of Nephrology, Hochtaunuskliniken, Zeppelinstrasse 32, 61352, Bad Homburg, Germany.
J Cardiothorac Surg. 2020 Jan 28;15(1):27. doi: 10.1186/s13019-020-1059-8.
After elective cardiac surgery a postoperative anticoagulation is obligatory. With critically ill patients the conventional anticoagulation standard heparin is sometimes impossible, e.g. based on HIT II. Then, argatroban is currently a possible alternative, however, due to its impaired metabolism in critically ill patients, anticoagulation effect is harder to anticipate, thus resulting in higher bleeding risk. Furthermore, to date no antidote is available. Hence, severe postoperative bleeding incidents under anticoagulation are commonly mono-causal attributed to the anticoagulation itself. This study concentrates on the number of well-defined postoperative bleeding incidents before any anticoagulation started, then actually under argatroban as well as compared to those under heparin (or switched from heparin to argatroban).
Retrospective study including 215 patients undergoing elective cardiac surgery with a postoperative stay in ICU ≥48 h. Postoperative bleeding complications before and after start of anticoagulation were evaluated. Definition of bleeding complications were: decrease of hemoglobin by more than 2 g/dl without dilution (mean value of volume balance plus one standard deviation) and/or increased need of red blood cell transfusion/day (average transfusion rate + 2 standard deviations).
Within the study group of 215 patients, 143 were treated with heparin, 43 with argatroban, 29 switched from heparin to argatroban. Overall, 26.5% (57/215) postoperative bleeding complications occurred. In 54.4% (31/57) bleeding complications occurred before start of anticoagulation; in 43.6% (26/57) after. Of these, 14 bleeding incidents occurred under heparin 9.8% (14/143), 6 under argatroban 14% (6/43) and 6 switched 20.7% (6/29). Higher bleeding complications before start of anticoagulation was related to concomitant factors influencing the overall bleeding risk; e.g. score of severity of illness. These observations further correlate with postoperative, but not anticoagulation induced mortality rate of 2.8% of then given heparin, 20.9% then argatroban, 20.7% then switched.
Postoperative bleeding complications cannot simply be attributed to anticoagulation since occurring often before anticoagulation was started. The risk for bleeding complications after start of anticoagulation was quite comparable for argatroban and heparin. Accordingly, the influence of argatroban on bleeding complications in the postoperative period may be less significant than previously thought.
择期心脏手术后必须进行术后抗凝。对于重症患者，传统的抗凝标准药物肝素有时无法使用，例如基于肝素诱导的血小板减少症II型（HIT II）的情况。此时，阿加曲班目前是一种可能的替代药物，然而，由于其在重症患者中代谢受损，抗凝效果更难预测，从而导致出血风险更高。此外，迄今为止尚无解毒剂。因此，抗凝治疗下的严重术后出血事件通常被单一归因于抗凝本身。本研究集中于在开始任何抗凝治疗之前、实际使用阿加曲班期间以及与使用肝素（或从肝素转换为阿加曲班）期间明确界定的术后出血事件的数量。
回顾性研究纳入215例接受择期心脏手术且术后在重症监护病房（ICU）停留≥48小时的患者。评估抗凝治疗开始前后的术后出血并发症。出血并发症的定义为：血红蛋白下降超过2 g/dl且无血液稀释（容量平衡平均值加一个标准差）和/或每日红细胞输注需求增加（平均输注率+2个标准差）。
在215例患者的研究组中，143例接受肝素治疗，43例接受阿加曲班治疗，29例从肝素转换为阿加曲班治疗。总体而言，发生了26.5%（57/215）的术后出血并发症。在54.4%（31/57）的出血并发症发生在抗凝治疗开始之前；43.6%（26/57）发生在之后。其中，14例出血事件发生在肝素治疗期间，占9.8%（14/143），6例发生在阿加曲班治疗期间，占14%（6/43），6例转换治疗的患者中发生6例，占20.7%（6/29）。抗凝治疗开始前较高的出血并发症与影响总体出血风险的伴随因素有关；例如疾病严重程度评分。这些观察结果进一步与术后死亡率相关，但与抗凝诱导的死亡率无关，当时使用肝素的患者死亡率为2.8%，使用阿加曲班的为20.9%，转换治疗的为20.7%。
术后出血并发症不能简单地归因于抗凝治疗，因为其常常在抗凝治疗开始之前就已发生。阿加曲班和肝素在抗凝治疗开始后出血并发症的风险相当。因此，阿加曲班对术后出血并发症的影响可能比之前认为的要小。
