Groene Philipp, Wiederkehr Tobias, Kammerer Tobias, Möhnle Patrick, Maerte Melanie, Bayer Andreas, Görlinger Klaus, Rehm Markus, Schäfer Simon T
Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
Institute for Anaesthesiology and Pain Therapy, HDZ NRW, Bad Oeynhausen, Germany.
Transfus Med Hemother. 2020 Apr;47(2):167-174. doi: 10.1159/000502016. Epub 2019 Aug 16.
Fibrinogen concentrates are widely used to restore clot stability in situations of bleeding. Fibrinogen preparations are produced using different production methods, resulting in different compounds. Thus, different preparations might have a distinct impact on blood coagulation. We tested the effect of fibrinogen concentrates Haemocomplettan® (CSL Behring, Marburg, Germany) and fibryga® (Octapharma GmbH, Langenfeld, Germany) on the impairments induced by 60% dilutional coagulopathy in vitro.
The influence of the fibrinogen concentrates fibryga® and Haemocomplettan® on colloid (gelatine, hydroxyethyl starch [HES], albumin)-induced or crystalloid (Ringer's acetate)-induced dilutional coagulopathy was analysed using rotational thromboelastometry (ROTEM®) and standard laboratory tests. The following experimental conditions were analysed in vitro: whole blood, 60% dilution (40% blood and 60% diluent) ± 50 or 100 mg/kg fibryga® or Haemocomplettan®, respectively.
Dilution with either diluent resulted in prolonged clotting time (CT) in an extrinsic activated test (CT) and decreased maximum clot firmness (MCF) as expressed, e.g., by gelatine: (59.5 s [62/54.8] vs. 95 s [102.8/86.8]; < 0.001 and 14 mm [16/10.5] vs. 3 mm [4-3]; < 0.001). Substitution after 60% dilution with HES resulted in no difference between the preparations, except for shorter thrombin time with fibryga® (14 s [15/14] vs. 18 s [18.8/17]; = 0.0093; low dose). CT was higher with Haemocomplettan® in a gelatine-induced dilution (51 s [54.5/47.5] vs. 63 s [71/60.3]; = 0.0202; low dose) whereas thrombin time was lower with fibryga® (19.5 s [20.8/19] vs. 27 s [29/25.3]; = 0.0017). In dilution with albumin, differences in CT (69 s [76.5/66] vs. 56 s [57/53.3]; = 0.0114; low dose) and thrombin time (18 s [18/17] vs. 24.5 s [25.8/24]; = 0.0202; low dose) were seen. In dilution with crystalloid solution, again differences in CT (53.5 s [57.8/53] vs. 45 s [47/43]; = 0.035; low dose) and thrombin time (17 s [17/16] vs. 23.5 s [24/23]; = 0.0014; low dose) were seen. Fibrinogen levels were more increased by high-dose substitution of both preparations.
Based on this data it can be stated that both fibryga® and Haemocomplettan® had the same performance in our in vitro model except for CT and thrombin time.
纤维蛋白原浓缩剂在出血情况下被广泛用于恢复凝血稳定性。纤维蛋白原制剂采用不同的生产方法生产,导致成分不同。因此,不同的制剂可能对血液凝固有不同的影响。我们在体外测试了纤维蛋白原浓缩剂Haemocomplettan®(德国马尔堡CSL Behring公司)和fibryga®(德国朗根费尔德Octapharma GmbH公司)对60%稀释性凝血病所致损伤的影响。
使用旋转血栓弹力图(ROTEM®)和标准实验室检测方法,分析纤维蛋白原浓缩剂fibryga®和Haemocomplettan®对胶体(明胶、羟乙基淀粉[HES]、白蛋白)诱导或晶体(醋酸林格液)诱导的稀释性凝血病的影响。在体外分析了以下实验条件:全血、60%稀释(40%血液和60%稀释剂)分别±50或100mg/kg fibryga®或Haemocomplettan®。
用任何一种稀释剂进行稀释均导致外源性激活试验中的凝血时间(CT)延长,以及最大凝块硬度(MCF)降低,如明胶诱导的情况:(59.5秒[62/54.8]对95秒[102.8/86.8];<0.001,以及14毫米[16/10.5]对3毫米[4 - 3];<0.001)。60%稀释后用HES替代,除了fibryga®的凝血酶时间较短外,两种制剂之间无差异(14秒[15/14]对18秒[18.8/17];=0.0093;低剂量)。在明胶诱导的稀释中,Haemocomplettan®的CT较高(51秒[54.5/47.5]对63秒[71/60.3];=0.0202;低剂量),而fibryga®的凝血酶时间较低(19.5秒[20.8/19]对27秒[29/25.3];=0.0017)。在白蛋白稀释中,CT(69秒[76.5/66]对56秒[57/53.3];=0.0114;低剂量)和凝血酶时间(18秒[18/17]对24.5秒[25.8/24];=0.0202;低剂量)存在差异。在晶体溶液稀释中,CT(53.5秒[57.8/53]对45秒[47/43];=0.035;低剂量)和凝血酶时间(17秒[17/16]对23.5秒[24/23];=0.0014;低剂量)也存在差异。两种制剂的高剂量替代使纤维蛋白原水平升高更多。
基于这些数据可以表明,除了CT和凝血酶时间外,fibryga®和Haemocomplettan®在我们的体外模型中表现相同。