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在持续性全身炎症反应综合征情况下体外循环期间的抗凝:肝素的作用

Anticoagulation during extracorporeal circulation under conditions of an ongoing systemic inflammatory response syndrome: effects of heparin.

作者信息

Feindt Peter, Litmathe Jens, Boeken Udo, Gams Emmeran

机构信息

Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany.

出版信息

Perfusion. 2005 Jan;20(1):11-5. doi: 10.1191/0267659105pf776oa.

DOI:10.1191/0267659105pf776oa
PMID:15751665
Abstract

OBJECTIVE

Open-heart surgery with cardiopulmonary bypass (CPB) causes changes in haemostasis. Artificial surfaces are bioincompatible and, thus, may initiate a reaction similar to an acute inflammation. In some patients, this 'postperfusion syndrome' (PPS), which includes changes in haemostasis, is the beginning of a systemic inflammatory response syndrome (SIRS). However, it is not clear whether the changes in coagulation represent a consequence or a main cause of the inflammatory reaction. Thus, the aim of our study was to investigate the cascade of coagulation and the effects of heparin under special circumstances of an ongoing SIRS.

METHODS

In a prospective evaluation using standardized operative procedures with CPB, we compared Group A (control group with normal postoperative course, n =20) with Group B (patients with postoperative SIRS, n =12). At six time points beginning before and ending two days after surgery, we measured platelet counts, leucocyte counts and plasma levels of fibrinogen, factor XII and antithrombin III (ATIII), in addition to standard coagulation tests (PTT, TT and ACT). Furthermore, we determined parameters of inflammation, such as C-reactive protein, PCT, IL-6, IL-8, IL-10 and TNF-alpha.

RESULTS

In Group B (SIRS), we found a reduced anticoagulation during CPB with significantly lower values for PTT (60+/-7 versus 160+/-11 s), ACT (270+/-33 versus 532+/-44 s) TT (40+/-3 versus 150+/-15 s) compared to the control Group A. Simultaneously, we found a significant increase of factor XII in the SIRS group (191+/-16 versus 10+/-2%). There were no significant differences concerning the preoperative ATIII levels and the intraoperative dosage of heparin; the intraoperative decrease of fibrinogen, ATIII and platelets was comparable in both groups. Furthermore, we could see that significant changes of inflammatory parameters in the SIRS group (increasing levels of TNF-alpha, Il-6, IL-8 and IL-10) occurred at least 30 min after the observed reduction of anticoagulatory effect.

CONCLUSIONS

With our results, it could be demonstrated that the development of inflammatory complications after CPB is correlated to a significantly reduced intraoperative effect of heparin. As this reduction of anticoagulation significantly preceded the changes of inflammatory parameters in SIRS patients, we think that a hypercoagulatory state, especially in cases of ongoing inflammation, is an additional trigger of SIRS.

摘要

目的

体外循环(CPB)下心内直视手术会引起止血功能的变化。人工表面具有生物不相容性,因此可能引发类似于急性炎症的反应。在一些患者中,这种“灌注后综合征”(PPS),包括止血功能的变化,是全身炎症反应综合征(SIRS)的开端。然而,尚不清楚凝血功能的变化是炎症反应的结果还是主要原因。因此,我们研究的目的是在持续发生SIRS的特殊情况下,研究凝血级联反应以及肝素的作用。

方法

在一项采用标准化CPB手术操作的前瞻性评估中,我们将A组(术后病程正常的对照组,n = 20)与B组(术后发生SIRS的患者,n = 12)进行了比较。在手术前开始并在术后两天结束的六个时间点,除了标准凝血试验(PTT、TT和ACT)外,我们还测量了血小板计数、白细胞计数以及纤维蛋白原、因子Ⅻ和抗凝血酶Ⅲ(ATⅢ)的血浆水平。此外,我们还测定了炎症参数,如C反应蛋白、降钙素原、白细胞介素-6、白细胞介素-8、白细胞介素-10和肿瘤坏死因子-α。

结果

在B组(SIRS组)中,我们发现CPB期间抗凝作用降低,与对照组A相比,PTT(60±7秒对160±11秒)、ACT(270±33秒对532±44秒)、TT(40±3秒对150±15秒)的值显著降低。同时,我们发现SIRS组中因子Ⅻ显著增加(191±16对10±2%)。术前ATⅢ水平和术中肝素用量没有显著差异;两组术中纤维蛋白原、ATⅢ和血小板的降低情况相当。此外,我们可以看到,SIRS组中炎症参数的显著变化(肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8和白细胞介素-10水平升高)至少在观察到抗凝作用降低30分钟后才出现。

结论

根据我们的研究结果,可以证明CPB后炎症并发症的发生与术中肝素作用显著降低相关。由于这种抗凝作用的降低在SIRS患者炎症参数变化之前就已显著出现,我们认为高凝状态,尤其是在持续炎症的情况下,是SIRS的另一个触发因素。

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