Estimating the rate of thrombin and fibrin generation in vivo during cardiopulmonary bypass
Estimating the rate of thrombin and fibrin generation in vivo during cardiopulmonary bypass
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DOI：
10.1182/blood-2002-08-2400
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发表时间：
2003-06-01
期刊：
影响因子：
20.3
通讯作者：
Velan, T
中科院分区：
文献类型：
--
作者：
Chandler, WL;Velan, T
我们的目标是估计体内凝血酶和纤维蛋白的生成率，以更好地了解凝血是如何调节的。研究对象是 9 名接受体外循环 (CPB) 的男性。体内凝血酶、总纤维蛋白和可溶性纤维蛋白生成率基于凝血酶原激活肽 F1.2、凝血酶-抗凝血酶复合物、纤维蛋白肽 A 和可溶性纤维蛋白的测量水平，并结合考虑标志物清除、血液稀释、失血和输血的患者血管系统计算机模型。手术前，平均凝血酶生成率为 0.24 +/- 0.11 pmol/s。每个凝血酶分子又产生约100个纤维蛋白分子，其中1%是可溶性纤维蛋白。胸骨切开术或给予肝素后，凝血酶生成率没有变化，然后在 CPB 5 分钟后迅速增加 20 倍，达到 5.60 +/- 6.65 pmol/s (P = .00005)。在 CPB 早期，每个新凝血酶仅产生 4 个纤维蛋白分子，其中 35% 是可溶性纤维蛋白。在 CPB 的剩余时间内，凝血酶生成率为 2.14 +/- 1.88 pmol/s，缺血心脏再灌注后再次增加至 5.47 +/- 4.08 pmol/s (P = .00008)。用鱼精蛋白中和肝素后，凝血酶生成量仍然很高（5.34 +/- 4.01 pmol/s，P = .0002），总纤维蛋白生成量增加，而可溶性纤维蛋白生成量减少。手术后 2 小时，凝血酶和纤维蛋白生成率恢复到基线水平。我们得出的结论是，体外循环和缺血心脏的再灌注会导致非止血性凝血酶生成的爆发和纤维蛋白形成失调，而不仅仅是先前研究表明的凝血酶生成的稳定增加。 (C) 2003 年，美国血液学会。
Our objective was to estimate the in vivo rates of thrombin and fibrin generation to better understand how coagulation is regulated. Studied were 9 males undergoing cardiopulmonary bypass (CPB). The rates of thrombin, total fibrin, and soluble fibrin generation in vivo were based on measured levels of prothrombin activation peptide F1.2, thrombin-antithrombin complex, fibrinopeptide A, and soluble fibrin, combined with a computer model of the patient's vascular system that accounted for marker clearance, hemodilution, blood loss, and transfusion. Prior to surgery, the average thrombin generation rate was 0.24 +/- 0.11 pmol/s. Each thrombin molecule in turn generated about 100 fibrin molecules, of which 1% was soluble fibrin. The thrombin generation rate did not change after sternotomy or administration of heparin, then rapidly increased 20-fold to 5.60 +/- 6.65 pmol/s after 5 minutes of CPB (P = .00005). Early in CPB each new thrombin generated only 4 fibrin molecules, of which 35% was soluble fibrin. The thrombin generation rate was 2.14 +/- 1.88 pmol/s during the remainder of CPB, increasing again to 5.47 +/- 4.08 pmol/s after reperfusion of the ischemic heart (P = .00008). After heparin neutralization with protamine, thrombin generation remained high (5.34 +/- 4.01 pmol/s, P = .0002) and total fibrin generation increased, while soluble fibrin generation decreased. By 2 hours after surgery, thrombin and fibrin generation rates were returning to baseline levels. We conclude that cardiopulmonary bypass and reperfusion of the ischemic heart results in bursts of nonhemostatic thrombin generation and dysregulated fibrin formation, not just a steady increase in thrombin generation as suggested by previous studies. (C) 2003 by The American Society of Hematology.