Moore Hunter B, Moore Ernest E, Gonzalez Eduardo, Wiener Gregory, Chapman Michael P, Dzieciatkowska Monika, Sauaia Angela, Banerjee Anirban, Hansen Kirk C, Silliman Christopher
Department of Surgery, University of Colorado, Denver, CO.
Department of Surgery, University of Colorado, Denver, CO; Denver Health Medical Center, Denver, CO.
J Am Coll Surg. 2015 May;220(5):872-9. doi: 10.1016/j.jamcollsurg.2015.01.026. Epub 2015 Mar 31.
Prehospital resuscitation with crystalloid exacerbates fibrinolysis, which is associated with high mortality. We hypothesized that plasma compared with crystalloid resuscitation prevents hyperfibrinolysis in a tissue plasminogen activator (tPA)-rich environment via preservation of proteins essential for regulation of fibrinolysis.
Healthy individuals donated blood, which was assayed using a native (nonactivated) thrombelastography (TEG). Whole-blood was mixed with normal saline (NS) or platelet poor plasma (PPP) at progressive dilutions. Tissue plasminogen activator was added to promote a fibrinolytic environment. In a separate experiment, PPP was run through a 100 kDa filter and liquid remaining on top of the filter (TFP) and below the filter (BFP) was obtained. Whole blood was diluted by 50% with TFP, BFP, and NS and assayed with a tPA TEG challenge. The TFP and BFP were assayed for protein concentration and protein composition.
Normal saline and PPP dilution of whole blood without tPA did not affect clot lysis at 30 minutes (LY30) (NS Spearman's rho 0.300, p = 0.186 and PPP 0.294, p = 0.288). When tPA was added, NS dilution of whole blood increased LY30 in a percentage-dependent manner (0.844, p < 0.001), but did not significantly increase with PPP dilution (0.270, p = 0.202). The difference in LY30 from whole blood to diluted whole blood with PPP (mean change, -1.05, 95% CI, -9.42 to 7.33) was similar with TFP (1.23, 95% CI, -5.20 to 7.66, p = 0.992). However, both BFP (37.65, 95% CI 24.47 to 50.82, p = 0.001) and NS (47.36, 95% CI 34.3 to 60.45, p < 0.001) showed large increases in fibrinolysis compared with PPP.
Crystalloid and plasma dilution of whole blood does not increase fibrinolysis. However, NS dilution of whole blood increases susceptibility to tPA-mediated fibrinolysis. Plasma resuscitation, simulated by plasma dilution of whole blood, attenuates increased susceptibility to tPA-mediated fibrinolysis. The benefits of plasma resuscitation are mediated through preservation of plasma proteins.
使用晶体液进行院前复苏会加剧纤维蛋白溶解，这与高死亡率相关。我们推测，与晶体液复苏相比，血浆复苏可通过保留调节纤维蛋白溶解所必需的蛋白质，在富含组织型纤溶酶原激活剂（tPA）的环境中预防高纤维蛋白溶解。
健康个体献血，使用天然（未激活）血栓弹力图（TEG）进行检测。将全血以逐渐增加的稀释度与生理盐水（NS）或乏血小板血浆（PPP）混合。加入组织型纤溶酶原激活剂以促进纤维蛋白溶解环境。在另一个实验中，将PPP通过100 kDa滤器，获得滤器顶部残留的液体（TFP）和滤器下方的液体（BFP）。全血用TFP、BFP和NS分别稀释50%，并进行tPA TEG激发检测。对TFP和BFP进行蛋白质浓度和蛋白质组成分析。
在无tPA的情况下，全血用生理盐水和PPP稀释在30分钟时不影响凝块溶解（LY30）（生理盐水斯皮尔曼相关系数0.300，p = 0.186；PPP为0.294，p = 0.288）。加入tPA后，全血用生理盐水稀释以百分比依赖的方式增加LY30（0.844，p < 0.001），但用PPP稀释时无显著增加（0.270，p = 0.202）。全血与用PPP稀释的全血之间LY30的差异（平均变化，-1.05，95%可信区间，-9.42至7.33）与TFP相似（1.23，95%可信区间，-5.20至7.66，p = 0.992）。然而，与PPP相比，BFP（37.65，95%可信区间24.47至50.82，p = 0.001）和生理盐水（47.36，95%可信区间34.3至60.45，p < 0.001）均显示纤维蛋白溶解大幅增加。
全血用晶体液和血浆稀释不会增加纤维蛋白溶解。然而，全血用生理盐水稀释会增加对tPA介导的纤维蛋白溶解的易感性。通过全血用血浆稀释模拟的血浆复苏可减弱对tPA介导的纤维蛋白溶解增加的易感性。血浆复苏的益处是通过保留血浆蛋白介导的。
