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肝素-血管性血友病因子相互作用与常规止血检验——体外循环中出血预测的挑战。

The heparin-von Willebrand factor interaction and conventional tests of haemostasis - the challenges in predicting bleeding in cardiopulmonary bypass.

机构信息

Department of Immunology and Inflammation, Imperial College London, London, UK.

Department of Haematology, Royal Brompton & Harefield NHS Foundation Trust, London, UK.

出版信息

Br J Haematol. 2021 Mar;192(6):1073-1081. doi: 10.1111/bjh.17263. Epub 2020 Dec 5.

Abstract

Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single-centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen-binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non-significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase-thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti-Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.

摘要

出血是体外循环(CPB)的一种严重并发症,尽管常规进行抗凝监测。这可能是多因素的。在这项对 30 名接受 CPB 手术的患者进行的前瞻性单中心队列研究中,我们的目的是描述 CPB 手术期间和之后 von Willebrand 因子(VWF)功能、血小板相互作用和整体凝血变化的特征,并确定是否可以预测出血。在 CPB 手术前、中、后六个时间点采集样本。我们观察到 VWF 抗原(VWF:Ag)在整个手术过程中显著升高,并在手术后持续升高。绝对 VWF 胶原结合测定(VWF:CB)和 VWF 瑞斯托菌素辅因子(VWF:RCo)显著升高,但 VWF:CB/VWF:Ag 和 VWF:Ag/VWF:RCo 显著降低(P=0.0015 和 P=0.0143),表明大聚体的丢失。我们在肝素化后检测到 VWF:RCo 有丢失的非显著趋势,在鱼精蛋白逆转后有显著恢复,这可能反映了肝素的直接作用。肝素酶血栓弹性图(TEG)显示,肝素给药后 R 和 K 时间显著增加,α角和最大振幅下降。在用鱼精蛋白后,这些参数均显著改善(P=0.007 和 P=0.0054)。活化凝血时间(ACT)和肝素抗 Xa 水平相关性差;两者均不能预测临床显著出血。这些参数均与术中失血量或血液制品替代需求无关。

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