冻干血浆减轻了血红蛋白基氧载体（HBOC-201）在复苏出血和血液稀释模型中的稀释效应。

Freeze-dried plasma mitigates the dilution effects of a hemoglobin-based oxygen carrier (HBOC-201) in a model of resuscitation for hemorrhage and hemodilution.

机构信息

From the United States Army Institute of Surgical Research, JBSA-Fort Sam Houston (G.C.P., C.S.M., A.S.T., J.A.B., A.E.P., A.P.C.)., Houston, Texas.

出版信息

J Trauma Acute Care Surg. 2019 Jul;87(1S Suppl 1):S83-S90. doi: 10.1097/TA.0000000000002317.

DOI:10.1097/TA.0000000000002317

PMID:31246911

Abstract

BACKGROUND

Hemoglobin-based oxygen carriers (HBOCs) have proven useful for supplementing oxygen delivery when red cells are unavailable; however, HBOCs do not promote hemostasis. The need for prehospital bridges to blood transfusion informed this study which sought to determine the impact of HBOCs on coagulation, with or without cotransfusion of freeze-dried plasma (FDP).

METHODS

Treatment was simulated in vitro by replacing whole blood volume (or whole blood prediluted with 25% plasmalyte A as a hemodilution model) with HBOC-201, FDP, or both at ratios of 10% to 50% of original volume. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, complete blood count, viscosity, thromboelastography (TEG), and platelet adhesion to collagen under flow were evaluated. Subsequently, tissue plasminogen activator was added to model hemorrhagic shock effects on fibrinolysis.

RESULTS

Substituting blood with HBOC resulted in dose-dependent decreases in fibrinogen and cells, which lengthened PT (+61% at highest dose) and aPTT (+40% at highest dose) and produced TEG parameters consistent with dilutional coagulopathy. While substituting blood with FDP decreased cell counts accordingly, fibrinogen, PT, aPTT, and TEG parameters were not statistically changed. When HBOC and FDP were combined 1:1 for volume replacement, observed HBOC-only detriments were mitigated: PT and aPTT were increased by 17% and 11%, respectively, at the highest doses. In prediluted samples, similar trends were seen with exacerbated differences. Platelet adhesion to collagen was directly affected by hematocrit. Samples containing both HBOC and tissue plasminogen activator were highly susceptible to fibrinolysis.

CONCLUSION

A dose equivalent to 1 unit to 2 units each of HBOC-201 and FDP had a modest impact on functional coagulation measures and is reasonable to consider for clinical study as a part of early transfusion intervention. Higher doses may impart hemodilution risks similar to resuscitation with crystalloid or other colloids in coagulation-compromised patients. Further study of HBOC effects on fibrinolysis is also indicated.

STUDY TYPE

In vitro laboratory study.

摘要

背景

血红蛋白基氧载体 (HBOCs) 已被证明在红细胞不可用时可有效补充氧气输送；然而，HBOCs 不会促进止血。本研究旨在确定 HBOCs 对凝血的影响，需要在院前将血液输送作为桥梁，因此研究了 HBOC 与冻干血浆 (FDP) 同时输注或不同时输注对凝血的影响。

方法

通过用 HBOC-201、FDP 或两者以 10% 至 50% 的原始体积比例替代全血体积（或用 25% plasmalyte A 预稀释的全血作为血液稀释模型）来模拟体外治疗。评估凝血酶原时间 (PT)、激活部分凝血活酶时间 (aPTT)、纤维蛋白原、全血细胞计数、粘度、血栓弹性图 (TEG) 和血小板在流动下对胶原蛋白的黏附。随后，加入组织型纤溶酶原激活剂模拟出血性休克对纤维蛋白溶解的影响。

结果

用 HBOC 替代血液会导致纤维蛋白原和细胞的剂量依赖性下降，从而使 PT（最高剂量时增加 61%）和 aPTT（最高剂量时增加 40%）延长，并产生与稀释性凝血功能障碍一致的 TEG 参数。用 FDP 替代血液会相应降低细胞计数，但纤维蛋白原、PT、aPTT 和 TEG 参数没有统计学上的变化。当 HBOC 和 FDP 以 1:1 的体积比混合替代时，观察到的 HBOC 单一损害得到缓解：最高剂量时 PT 和 aPTT 分别增加 17% 和 11%。在预稀释样本中，也出现了类似的趋势，差异更加明显。血小板对胶原蛋白的黏附直接受到血细胞比容的影响。含有 HBOC 和组织型纤溶酶原激活剂的样本极易发生纤维蛋白溶解。