Comparison of the efficacy of two human fibrinogen concentrates to treat dilutional coagulopathy in vitro

Both congenital and acquired fibrinogen deficiency can be safely treated with administration of fibrinogen concentrate.

The aim of this study was to test the efficacy of a new fibrinogen product (Fibryga) compared to a licensed product (Haemocomplettan) in an in vitro model of dilutional coagulopathy.

Ten blood specimens from healthy volunteers were diluted 1:1 with balanced crystalloid solution and subsequently supplemented with each fibrinogen concentrate at a dose replicating in vivo supplementation (50?mg kg^?1). Changes in clot firmness (FIBTEM and EXTEM assay), as well as changes in the fibrinogen antigen level, fibrinogen activity, factor XIII level and fibronectin levels were assessed at baseline, after dilution and after adding fibrinogen concentrate.

There was no significant difference between the drugs in their in vitro ability to improve clot firmness in the FIBTEM assay (Fibryga: mean MCF 14.4?mm (SD 3.4?mm) vs. Haemocomplettan: MCF 14.1?mm (2.4); p?=?.584). Fibryga led to significantly higher clot firmness in EXTEM MCF: 56.7?mm (3.8) vs. 53.7?mm (3.7); p?p??1 (SD 0.002?g L^?1) vs. 0.002?g L^?1 (SD 0.002?g L^?1; p?This is the first study to demonstrate that Fibryga and Haemocomplettan have similar efficacy in improving clot firmness in a dilutional hypofibrinogenemia model in vitro.     

Tailoring haemostatic treatment to patient requirements – an update on monitoring haemostatic response using thrombelastography

Summary.  Currently, there is no single haemostasis laboratory test that has the capacity to accurately illustrate the clinical effects of procoagulant or anticoagulant interventions. Although the time course of thrombin generation in plasma and the endogenous thrombin potential (ETP) may be useful coagulation parameters, clotting involves components other than thrombin (e.g. platelets, fibrinogen). The continuous coagulation profiles of thrombelastography may provide a more accurate reflection of in vivo biology, covering initiation, development and final clot strength during whole blood clot formation. This method has helped to clarify the mechanism of action of whole blood clot formation, demonstrating the differences from clotting in plasma, and the importance of platelets and tissue factor titrations. It has also been used to investigate hypocoagulation (in haemophilia A, rare coagulation disorders, anticoagulant therapy and dilutional coagulopathy), hypercoagulation and the ex vivo testing of haemostatic interventions. Thrombelastography has been shown to reflect the clinical efficacy of activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) in patients with haemophilia A with inhibitors and in patients with acquired haemophilia. Overall, tailoring laboratory assays to illustrate and correlate with clinical phenotypes is essential for effective coagulation monitoring. Applying an algorithm of preoperative, perioperative and postoperative tests, including thrombelastography, may enable physicians to achieve this.     

CYP2C19基因多态性与介入治疗后氯吡格雷药物疗效的相关性研究

目的探讨PCI术后CYP2C19基因多态性与不同剂量氯吡格雷药物效果的相关性。方法通过基因芯片检测技术,筛选PCI术后CYP2C19基因突变为CYP2C19*2/*2、CYP2C19*2/*3或CYP2C19*3/*3的患者67例,随机分为常规组22例、2倍组22例和3倍组23例。常规组75 mg氯吡格雷、2倍组150 mg氯吡格雷、3倍组225 mg氯吡格雷,1次/d。分别于PCI术后1、3、6个月通过血栓弹力图检测各组氯吡格雷药物抑制率及再发心血管缺血事件发生率。结果 PCI术后6个月内,2倍组和3倍组患者心血管缺血事件发生率较常规组明显降低(81.8%vs 31.8%vs 21.7%,P<0.01),2倍组与3倍组比较差异无统计学意义(P>0.05)。术后1、3、6个月2倍组和3倍组氯吡格雷药物抑制率较常规组显著升高(P<0.01),2倍组与3倍组比较差异无统计学意义(P>0.05)。3组出血风险比较差异无统计学意义(P>0.05)。结论 CYP2C19基因变异患者增加氯吡格雷药物服用剂量,可在一定程度上提高血小板的抑制,降低心血管缺血事件发生率,且不增加出血事件的发生率。     

血小板二磷酸腺苷受体H2单体型与阿司匹林抗血小板功能学监测关联的研究

目的探讨血小板二磷酸腺苷受体(P2Y12)H2单体型对中国老年汉族患者阿司匹林抑制血小板聚集功能及血小板计数的影响。方法入选北京万寿路地区服用阿司匹林老年汉族患者431例,使用美国Sequenom系统单核苷酸多态性分型技术对P2Y12H1/H2单体型进行鉴定。采用花生四烯酸诱导的光比浊和血栓弹力图法、二磷酸腺苷诱导的光比浊和血栓弹力图法、血小板活化标记物血小板激活复合物1、CD62P等血小板功能检测,对P2Y12H2单体型与血小板计数及阿司匹林抗血小板聚集功能进一步行相关分析。结果 431例患者中,P2Y12H1/H1基因型285例,H1/H2基因型136例,H2/H2基因型10例。H1/H1、H1/H2、H2/H2基因型血小板计数分别为(216.09±58.76)×109/L,(195.06±55.16)×109/L,(164.90±46.12)×109/L,差异有统计学意义(P<0.01)。H1/H2+H2/H2与H1/H1比较,经年龄、性别校正后,多因素回归分析仍提示血小板计数与H2相关联(P=0.005)。结论 P2Y12H2单体型对阿司匹林的抗血小板作用无明显影响。携带P2Y12H2单体型患者的血小板计数明显低于H1型患者,提示P2Y12H2单体型可能是正常人群血小板计数低下的一个基因学标志。     

冠心病介入治疗患者氯吡格雷抵抗的研究进展

多年来临床试验证实氯吡格雷作为重要的抗血小板聚集药,在心血管疾病的预防治疗中起着重要作用。但氯吡格雷抵抗的出现限制了其临床效果。现就氯吡格雷抵抗的定义、机制,以及氯吡格雷抵抗的检测方法包括血栓弹力图进行综述。     

酸血症时凝血功能变化的研究

目的 观察酸血症时凝血功能变化,对比不同检测方法对酸血症时凝血功能的诊断价值.方法 将12只家猪分为对照组和酸血症组,在控制性放出实验动物总血容量的35%后,阻断其自主呼吸并配合呼吸机制造酸血症模型.测定基础时间点和酸血症模型制作成功180 min后血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)以及血栓弹力图仪(TEG)各项参数,并行对照分析.结果 与基础值相比,180 min后实验组血乳酸浓度上升了220%,血小板数量降低了30%,血浆纤维蛋白浓度降低了27%(P ＜0.05),实验组PT、APTT和TT均无显著变化.TEG各项参数中,R时间无显著变化,K时间出现显著延长,α角和MA值均显著减小(P＜0.05).结论 在酸血症时,实验动物出现血低凝状态,其原因与血凝块合成速率下降和血凝块强度的降低有关.TEG在创伤合并酸血症时对凝血功能检测的敏感性优于PT、APTT等方法.     

Whole blood coagulation in children with thrombocytopenia and the response to platelet replacement, recombinant factor VIIa, and a potent factor VIIa analogue

The present study evaluated dynamic coagulation profiles, platelet aggregation, and thrombin generation in whole blood (WB) from eight children with thrombocytopenia during chemotherapy, and the haemostatic potential of platelets (+60 × 10⁹/l), recombinant factor VIIa (rFVIIa – NovoSeven^®), and a potent rFVIIa analogue (NN1731) both at 1 and 4 μg/ml. Dynamic WB coagulation profiles were recorded by thrombelastometry employing activation with tissue factor (TF – Innovin^®) at low concentrations. The baseline WB coagulation patterns were characterised by a prolonged clotting time (CT) and a pronounced reduction in clot propagation (MaxVel). WB platelet aggregation signal was five times lower in the study group compared with measurements in modelled thrombocytopenic WB from healthy volunteers. In vitro addition of fresh platelets reversed the coagulopathy. Addition of rFVIIa induced no significant changes in the thrombelastographic profile, whereas spiking with NN1731 shortened the CT significantly. The changes in WB thrombin generation reflected the changes in the MaxVel. In modeled thrombocytopenic WB from healthy individuals, both rFVIIa and NN1731 exhibited a pronounced haemostatic effect with NN1731 showing greater potency than rFVIIa. Compromised platelet function in the study group was assumingly responsible for the weakened haemostatic potential of rFVIIa as well as that of NN1731.