阿加曲班用于血液回收系统抗凝的体外研究

Argatroban for anticoagulation of a blood salvage system - an ex-vivo study.

作者信息

Beiderlinden Martin, Brau Carsten, di Grazia Santo, Wehmeier Michael, Treschan Tanja A

机构信息

Klinik für Anästhesiologie, Marienhospital Osnabrück, Osnabrück, Germany.

Institut für Laboratoriumsmedizin, Marienhospital Osnabrück, Osnabrück, Germany.

出版信息

BMC Anesthesiol. 2016 Jul 15;16(1):37. doi: 10.1186/s12871-016-0204-3.

DOI:10.1186/s12871-016-0204-3

PMID:27418211

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4946229/

Abstract

BACKGROUND

Blood salvage systems help to minimize intraoperative transfusion of allogenic blood. So far no data is available on the use of argatroban for anticoagulation of such systems. We conducted an ex-vivo trial to evaluate the effectiveness of three different argatroban doses as compared to heparin and to assess potential residual anticoagulant in the red cell concentrates.

METHODS

With ethical approval and individual informed consent, blood of 23 patients with contraindications for use of blood salvage systems during surgery was processed by the Continuous-Auto-Transfusion-System (C.A.T.S. ® Cell Saver System, Fresenius Kabi, Bad Homburg, Germany) using 5,50 or 250 mg of argatroban or 25.000 U of heparin in 1000 ml saline for anticoagulation of the system. Emergency and high-quality washing modes were applied in random order. Patency of the system and residual amount of anticoagulants in the re-transfusion bag were measured. The collected blood was not re-infused, but only used for analysis of hematocrit, heparin and argatroban concentrations.

RESULTS

Patency of the system was provided by all anticoagulants except for 3/8 cases with 5 mg of argatroban. Residual anticoagulant was found in 2/10 (20 %) heparin samples in two different patients (1 emergency and 1 high-quality washing) and in all argatroban samples. High quality washing eliminated 89-95 % and emergency washing 60-90 % of the initial argatroban concentration. Residual argatroban concentrations ranged from 55 ng ml(-1) to 6810 ng ml(-1), with initial argatroban concentrations of 5 and 250 mg, respectively.

CONCLUSION

The C.A.T.S. does not reliably remove heparin and should therefore not be used in HIT patients. Anticoagulation with 50 and 250 mg argatroban, maintains the systems patency and is significantly removed during washing. In this ex-vivo study a concentration of 50 μg ml(-1) argatroban provided the best ratio of system patency and residual argatroban concentration. Additional dose-finding studies with different blood salvage systems are needed to evaluate the optimal argatroban concentration.

摘要

背景

血液回收系统有助于减少术中异体输血。目前尚无关于阿加曲班用于此类系统抗凝的数据。我们进行了一项体外试验，以评估三种不同剂量阿加曲班与肝素相比的有效性，并评估红细胞浓缩物中潜在的残留抗凝剂。

方法

在获得伦理批准和个人知情同意后，使用连续自动输血系统（C.A.T.S.®细胞回收系统，费森尤斯卡比公司，德国巴特洪堡）对23例手术期间有血液回收系统使用禁忌证患者的血液进行处理，在1000ml生理盐水中分别加入5mg、50mg或250mg阿加曲班或25000U肝素用于系统抗凝。紧急清洗模式和高质量清洗模式随机应用。测量系统的通畅性和再输血袋中抗凝剂的残留量。收集的血液不进行回输，仅用于分析血细胞比容、肝素和阿加曲班浓度。

结果

除3/8例使用5mg阿加曲班的情况外，所有抗凝剂均能保持系统通畅。在两名不同患者（1例紧急清洗和1例高质量清洗）的2/10（20%）肝素样本以及所有阿加曲班样本中发现有残留抗凝剂。高质量清洗可消除初始阿加曲班浓度的89 - 95%，紧急清洗可消除60 - 90%。初始阿加曲班浓度分别为5mg和250mg时，残留阿加曲班浓度范围为55ng/ml至6810ng/ml。

结论

C.A.T.S.不能可靠地清除肝素，因此不应在肝素诱导的血小板减少症（HIT）患者中使用。50mg和250mg阿加曲班抗凝可维持系统通畅，且在清洗过程中可被显著清除。在这项体外研究中，50μg/ml的阿加曲班浓度在系统通畅性和残留阿加曲班浓度之间提供了最佳比例。需要对不同的血液回收系统进行额外的剂量探索研究，以评估最佳阿加曲班浓度。