在猪创伤24小时模型中，纤维蛋白原浓缩物不会抑制内源性纤维蛋白原的合成。

Fibrinogen concentrate does not suppress endogenous fibrinogen synthesis in a 24-hour porcine trauma model.

作者信息

Zentai Christian, Braunschweig Till, Schnabel Jonas, Rose Michael, Rossaint Rolf, Grottke Oliver

机构信息

From the Department of Anesthesiology (C.Z., J.S., R.R., O.G.), Institute for Laboratory Animal Science (C.Z.), and Department of Pathology (T.B., M.R.), RWTH Aachen University Hospital, Aachen, Germany.

出版信息

Anesthesiology. 2014 Oct;121(4):753-64. doi: 10.1097/ALN.0000000000000315.

DOI:10.1097/ALN.0000000000000315

PMID:24866407

Abstract

BACKGROUND

Fibrinogen concentrate may reduce blood loss after trauma. However, its effect on endogenous fibrinogen synthesis is unknown. The authors investigated the effect of exogenous human fibrinogen on endogenous fibrinogen metabolism in a 24-h porcine trauma model.

METHODS

Coagulopathy was induced in 20 German Landrace pigs by hemodilution and blunt liver injury. Animals were randomized to receive fibrinogen concentrate (100 mg/kg; infusion beginning 20 min postinjury and lasting approximately 10 min) or saline. Fibrinogen concentration, thromboelastometry, and quantitative reverse transcriptase polymerase chain reaction of fibrinogen genes in liver tissue samples were recorded. Internal organs were examined histologically for emboli.

RESULTS

Coagulation parameters were impaired and plasma fibrinogen concentrations were reduced before starting infusion of fibrinogen concentrate/saline. Twenty minutes after starting infusion, exogenous fibrinogen supplementation had increased plasma fibrinogen concentration versus controls (171 ± 19 vs. 63 ± 10 mg/dl [mean ± SD for Multifibren U]; 185 ± 30 vs. 41 ± 4 mg/dl [Thrombin reagent]; P < 0.05 for both comparisons). The between-group difference in plasma fibrinogen concentration diminished thereafter, with maximum concentrations in both groups observed at approximately 24 h, that is, during the acute-phase reaction after trauma. Fibrinogen supplementation did not down-regulate endogenous fibrinogen synthesis (no between-group differences in fibrinogen messenger RNA). Total postinjury blood loss was significantly lower in the fibrinogen group (1,062 ± 216 vs. 1,643 ± 244 ml; P < 0.001). No signs of thromboembolism were observed.

CONCLUSIONS

Administration of human fibrinogen concentrate did not down-regulate endogenous porcine fibrinogen synthesis. The effect on plasma fibrinogen concentration was most pronounced at 20 min but nonsignificant at approximately 24 h.

摘要

背景

纤维蛋白原浓缩物可能减少创伤后的失血。然而，其对内源性纤维蛋白原合成的影响尚不清楚。作者在一个24小时的猪创伤模型中研究了外源性人纤维蛋白原对内源性纤维蛋白原代谢的影响。

方法

通过血液稀释和钝性肝损伤诱导20头德国长白猪发生凝血障碍。将动物随机分为接受纤维蛋白原浓缩物（100mg/kg；伤后20分钟开始输注，持续约10分钟）或生理盐水组。记录肝组织样本中的纤维蛋白原浓度、血栓弹力图和纤维蛋白原基因的定量逆转录聚合酶链反应。对内部器官进行组织学检查以寻找栓子。

结果

在开始输注纤维蛋白原浓缩物/生理盐水之前，凝血参数受损，血浆纤维蛋白原浓度降低。开始输注20分钟后，与对照组相比，补充外源性纤维蛋白原使血浆纤维蛋白原浓度升高（171±19对63±10mg/dl[Multifibren U的均值±标准差]；185±30对41±4mg/dl[凝血酶试剂]；两组比较P均<0.05）。此后，两组间血浆纤维蛋白原浓度差异减小，两组在约24小时时观察到最大浓度，即在创伤后的急性期反应期间。补充纤维蛋白原并未下调内源性纤维蛋白原合成（纤维蛋白原信使核糖核酸无组间差异）。纤维蛋白原组伤后总失血量显著更低（1062±216对1643±244ml；P<0.001）。未观察到血栓栓塞迹象。