Chandler Wayne L, Velan Tomas
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195-7110, USA.
Blood. 2003 Jun 1;101(11):4355-62. doi: 10.1182/blood-2002-08-2400. Epub 2002 Dec 12.
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 =.000 05). 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 =.000 08). 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.
我们的目标是评估体内凝血酶和纤维蛋白的生成速率，以便更好地理解凝血过程是如何被调节的。研究对象为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的生成速率是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，结合患者血管系统的计算机模型，该模型考虑了标志物清除、血液稀释、失血和输血情况。手术前，凝血酶生成的平均速率为0.24±0.11 pmol/s。每个凝血酶分子依次生成约100个纤维蛋白分子，其中1%为可溶性纤维蛋白。胸骨切开术或给予肝素后，凝血酶生成速率没有变化，然后在CPB开始5分钟后迅速增加20倍，达到5.60±6.65 pmol/s（P = 0.000 05）。在CPB早期，每个新生成的凝血酶仅生成4个纤维蛋白分子，其中35%为可溶性纤维蛋白。在CPB剩余时间内，凝血酶生成速率为2.14±1.88 pmol/s，在缺血性心脏再灌注后再次增加至5.47±4.08 pmol/s（P = 0.000 08）。用鱼精蛋白中和肝素后，凝血酶生成仍处于高水平（5.34±4.01 pmol/s，P = 0.0002），总纤维蛋白生成增加，而可溶性纤维蛋白生成减少。术后2小时，凝血酶和纤维蛋白生成速率恢复到基线水平。我们得出结论，体外循环和缺血性心脏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，并非如先前研究所表明的那样只是凝血酶生成的稳定增加。
