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纤维蛋白原浓缩物 Haemocomplettan(瑞斯托)或因子 XIII 浓缩物 Fibrogammin 联合小剂量氨甲环酸可逆转由凝血酶或 FXa 抑制剂诱导的纤维蛋白不稳定性向纤维蛋白溶解的转变。

A fibrinogen concentrate Haemocomplettan (Riastap) or a Factor XIII concentrate Fibrogammin combined with a mini dose of tranexamic acid can reverse the fibrin instability to fibrinolysis induced by thrombin- or FXa-inhibitor.

机构信息

Department of Molecular Medicine and Surgery/Clinical Chemistry/Coagulation Research, Karolinska Institutet, Stockholm, Sweden.

出版信息

Br J Haematol. 2013 Mar;160(6):806-16. doi: 10.1111/bjh.12189. Epub 2013 Jan 30.

DOI:10.1111/bjh.12189
PMID:23360261
Abstract

To assess whether Haemocomplettan(®) (fibrinogen concentrate) or Fibrogammin(®) (Factor XIII concentrate) can be used to manage bleeding complications of antithrombotic treatment, we examined a normal plasma pool spiked with AR-H067637 (thrombin inhibitor) or rivaroxaban (activated factor X-inhibitor), to which one of the concentrates was added. Fibrin network permeability (Ks), images of Scanning Electron Microscopy (SEM) and Clot Lysis Time (CLT) were examined. Both inhibitors increased the Ks levels, which could be fully or partly reversed by Haemocomplettan(®) or Fibrogammin(®) respectively. However, these modified clots with tightened network remained non-resistant to fibrinolysis, shown as unaffected CLT. Tranexamic acid at a very low concentration (0·4 mg/ml) aided the two concentrates to stabilize the clots, where the prolongation of CLT was more pronounced for a lower dose than a higher dose of Haemocomplettan(®) while Fibrogammin(®) brought the greatest delay to CLT out of all additions. These observations were partly supported by SEM images, displaying alterations of fibrin fibre arrangement known to influence fibirinolysis. The in vitro data suggest that Haemocomplettan(®) or Fibrogammin(®) given in combination with a mini dose of tranexamic acid may slow down the natural clearance of fibrin clot by plasmin and thus prevent patients from haemorrhagic complications during antithrombotic therapy.

摘要

为了评估 Haemocomplettan(®)(纤维蛋白原浓缩物)或 Fibrogammin(®)(因子 XIII 浓缩物)是否可用于治疗抗血栓治疗的出血并发症,我们用 AR-H067637(凝血酶抑制剂)或利伐沙班(活化的因子 X 抑制剂)对正常血浆池进行了加标,然后向其中添加一种浓缩物。我们检查了纤维蛋白网络通透性(Ks)、扫描电子显微镜(SEM)图像和血栓溶解时间(CLT)。两种抑制剂均增加了 Ks 水平,Haemocomplettan(®)或 Fibrogammin(®) 可分别完全或部分逆转。然而,这些纤维蛋白网络收紧的改性血栓仍然对纤维蛋白溶解没有抵抗力,表现为 CLT 不受影响。非常低浓度(0.4mg/ml)的氨甲环酸有助于两种浓缩物稳定血栓,与较高剂量的 Haemocomplettan(®)相比,较低剂量的 Haemocomplettan(®)使 CLT 延长更为明显,而 Fibrogammin(®)使 CLT 延长的时间最长。这些观察结果部分得到 SEM 图像的支持,显示了纤维蛋白纤维排列的改变,已知这些改变会影响纤维蛋白溶解。体外数据表明,在联合使用小剂量氨甲环酸的情况下,给予 Haemocomplettan(®)或 Fibrogammin(®)可能会减缓纤溶酶对纤维蛋白凝块的自然清除速度,从而防止患者在抗血栓治疗期间发生出血并发症。

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