Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy
Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy
复制标题
DOI：
10.1111/j.1538-7836.2009.03460.x
复制
发表时间：
2009-07-01
影响因子：
10.4
通讯作者：
Sorensen, B.
中科院分区：
文献类型：
--
作者：
Fenger-Eriksen, C.;Tonnesen, E.;Sorensen, B.
背景资料：羟乙基淀粉130/0.4（HES）输注后引起稀释性凝血病的生化机制尚不清楚。目的：对羟乙基淀粉体内稀释30%后凝血功能障碍的机制进行详细的生化描述，对各种止血剂进行系统的体外试验，并研究获得性纤维蛋白原缺乏是凝血功能障碍最重要决定因素的假设。研究方法：在一项前瞻性临床研究中，对20例出血患者进行了动态全血凝块形成（通过血栓弹性测定法评估）、血小板计数、凝血酶生成以及血管性血友病因子、凝血因子II、FVII、FVIII、FIX、FX和FXIII活性的测量，该研究旨在研究HES体内替代失血量达到30%的目标水平。在用纤维蛋白原、凝血酶原复合物浓缩物（PCC）、FXIII、活化重组FVIIa（rFVIIa）、新鲜冷冻血浆和血小板进行离体加标实验后，进一步评价血栓弹性测定参数。结果：血液稀释降低了最大凝块硬度（MCF），而全血凝固时间（CT）和最大流速不受影响。所有凝血因子活性均降低。纤维蛋白原、FIB、FXIII和FX活性显著降低，低于稀释后的预期水平。内源性凝血酶潜力不变。体外添加纤维蛋白原使降低的MCF正常化并增加最大流速，而PCC、rFVIIa和血小板缩短了CT，但对降低的MCF没有影响。结论：获得性纤维蛋白原缺乏似乎是稀释性凝血病的主要决定因素，体外添加完全纠正了凝血病。
Background: The biochemical mechanisms causing dilutional coagulopathy following infusion of hydroxyethyl starch 130/0.4 (HES) are not known in detail. Objectives: To give a detailed biochemical description of the mechanism of coagulopathy following 30%in vivo dilution with HES, to present a systematic ex vivo test of various hemostatic agents, and to investigate the hypothesis that acquired fibrinogen deficiency constitutes the most important determinant of the coagulopathy. Methods: Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, thrombin generation, and the activities of von Willebrand factor, coagulation factor II, FVII, FVIII, FIX, FX and FXIII were measured in 20 bleeding patients enrolled in a prospective clinical study investigating in vivo substitution of blood loss with HES up to a target level of 30%. Thromboelastometry parameters were further evaluated after ex vivo spiking experiments with fibrinogen, prothrombin complex concentrate (PCC), FXIII, activated recombinant FVIIa (rFVIIa), fresh frozen plasma, and platelets. Results: Hemodilution reduced maximum clot firmness (MCF), whereas whole blood clotting time (CT) and maximum velocity remained unaffected. All coagulation factor activities were reduced. Fibrinogen, FII, FXIII and FX activities decreased significantly below the levels expected from dilution. The endogenous thrombin potential was unchanged. Ex vivo addition of fibrinogen normalized the reduced MCF and increased the maximum velocity, whereas PCC, rFVIIa and platelets shortened the CT but showed no effect on the reduced MCF. Conclusions: Acquired fibrinogen deficiency seems to be the leading determinant in dilutional coagulopathy, and ex vivo addition corrected the coagulopathy completely.