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监测肝素与抑肽酶联合应用时的活化凝血时间:使用Sonoclot对一种新型抑肽酶不敏感检测方法的体内评估

Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot.

作者信息

Ganter Michael T, Monn Antoinette, Tavakoli Reza, Genoni Michele, Klaghofer Richard, Furrer Lukas, Honegger Hanspeter, Hofer Christoph K

机构信息

Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital Zurich, Switzerland.

出版信息

Eur J Cardiothorac Surg. 2006 Aug;30(2):278-84. doi: 10.1016/j.ejcts.2006.05.016. Epub 2006 Jul 7.

DOI:10.1016/j.ejcts.2006.05.016
PMID:16828293
Abstract

OBJECTIVE

Kaolin-based activated clotting time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combined with aprotinin during cardiopulmonary bypass (CPB). However, aprotinin is known to prolong not only celite-based but also kaolin-based activated clotting time. Overestimation of activated clotting times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel 'aprotinin-insensitive' activated clotting time test has been developed for the SONOCLOT analyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin.

METHODS

Blood samples were taken from 44 elective cardiac surgery patients at the following measurement time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60 min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement time point, activated clotting time was assessed with HkACT and SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson's correlation, and ANOVA with post hoc Bonferroni-Dunn correction.

RESULTS

Monitoring anticoagulation with SaiACT showed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean+/-SD) were 44+/-118 s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4-T6; 89+/-152 s, P=0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r2=0.473 and 0.487, respectively; P=0.794), but was lower for HkACT after aprotinin administration (r2=0.481 and 0.361, respectively; P=0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACT and HkACT.

CONCLUSIONS

The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotinin.

摘要

目的

通过HEMOCHRON检测的基于高岭土的活化凝血时间(HkACT)是体外循环(CPB)期间单独监测肝素以及肝素与抑肽酶联合使用时的临床标准。然而,已知抑肽酶不仅会延长基于硅藻土的活化凝血时间,还会延长基于高岭土的活化凝血时间。活化凝血时间的高估意味着肝素抗凝治疗不足存在潜在危险风险。最近,已为SONOCLOT分析仪开发了一种新型的“抑肽酶不敏感”活化凝血时间检测方法(SaiACT)。我们研究的目的是评估在有肝素和抑肽酶存在的情况下接受CPB的患者中的SaiACT。

方法

从44例择期心脏手术患者在以下测量时间点采集血样:基线(T0);肝素化后CPB前(T1和T2);CPB期间,给予抑肽酶前(T3);给予抑肽酶后CPB 15、30和60分钟(T4、T5和T6);鱼精蛋白输注后(T7)。在每个测量时间点,用HkACT和SaiACT评估活化凝血时间,均重复测量两次。此外,测量Xa因子抑制率和抗凝血酶浓度。使用Bland和Altman分析、Pearson相关性分析以及带有事后Bonferroni-Dunn校正的方差分析进行统计分析。

结果

用SaiACT监测抗凝显示读数可靠。与既定的HkACT相比,在所有测量时间点SaiACT值均较低。在CPB期间但给予抑肽酶前(T3),SaiACT值(均值±标准差)比HkACT低44±118秒。然而,给予抑肽酶后CPB期间两种测量技术之间的差异显著增加(T4 - T6;89±152秒,P = 0.032)。给予抑肽酶前后,SaiACT的ACT测量值与抗Xa活性的相关性不变(r2分别为0.473和0.487;P = 0.794),但给予抑肽酶后HkACT的相关性较低(r2分别为0.481和0.361;P = 0.041)。给予抑肽酶后CPB期间,所有ACT值中有96%被HkACT分类为治疗性,但如果通过SaiACT测定ACT,则所有值中只有86%被分类为治疗性。SaiACT和HkACT的检测变异性相当。

结论

使用SaiACT可能会使肝素管理更一致,受抑肽酶影响较小,并且接受抑肽酶治疗的患者肝素给药相应增加。

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