Department of Paediatrics, Nara Medical University, Kashihara, Nara, Japan.
Course of Haemophilia Treatment & Pathology, Nara Medical University, Kashihara, Nara, Japan.
Br J Haematol. 2019 Nov;187(4):518-529. doi: 10.1111/bjh.16111. Epub 2019 Jul 23.
Simultaneous evaluation of coagulation and fibrinolysis facilitates an overall understanding of normal and pathological haemostasis. We established an assay for assessing clot formation and fibrinolysis simultaneously using clot waveform analysis by the trigger of a mixture of activated partial thromboplastin time reagent and an optimized concentration of tissue-type plasminogen activator (0·63 μg/ml) to examine the temporal reactions in a short monitoring time (<500 s). The interplay between clot formation and fibrinolysis was confirmed by analysing the effects of argatroban, tranexamic acid and thrombomodulin. Fibrinogen levels positively correlated with coagulation and fibrinolytic potential and initial fibrin clot formation was independent of plasminogen concentration. Plasminogen activator inhibitor-1-deficient (-def) and α2-antiplasmin-def plasmas demonstrated different characteristic hyper-fibrinolytic patterns. For the specificity of individual clotting factor-def plasmas, factor (F)VIII-def and FIX-def plasmas in particular demonstrated shortened fibrinolysis lag-times (FLT) and enhanced endogenous fibrinolysis potential in addition to decreased maximum coagulation velocity, possibly reflecting the fragile formation of fibrin clots. Tranexamic acid depressed fibrinolysis to a similar extent in FVIII-def and FIX-def plasmas. We concluded that the clot-fibrinolysis waveform analysis technique could sensitively monitor both sides of fibrin clot formation and fibrinolysis, and could provide an easy-to-use assay to help clarify the underlying pathogenesis of bleeding disorders in routine clinical practice.
同时评估凝血和纤溶有助于全面了解正常和病理止血。我们建立了一种使用血栓波形分析同时评估血栓形成和纤溶的方法，通过混合激活部分凝血活酶时间试剂和优化浓度的组织型纤溶酶原激活剂（0.63μg/ml）触发来检测短监测时间（<500s）内的时间反应。通过分析 Argatroban、氨甲环酸和血栓调节蛋白的作用证实了血栓形成和纤溶之间的相互作用。纤维蛋白原水平与凝血和纤溶潜能呈正相关，初始纤维蛋白血栓形成与纤溶酶原浓度无关。纤溶酶原激活物抑制剂-1 缺乏（-def）和α2-抗纤溶酶缺乏（α2-AP-def）血浆表现出不同的特征性高纤溶模式。对于个体凝血因子缺乏（F）血浆的特异性，特别是 FVIII-def 和 FIX-def 血浆表现出缩短的纤溶潜伏期（FLT）和增强的内源性纤溶潜能，除了最大凝血速度降低外，这可能反映了纤维蛋白血栓形成的脆弱性。氨甲环酸在 FVIII-def 和 FIX-def 血浆中对纤溶的抑制作用相似。我们得出结论，血栓-纤溶波形分析技术可以敏感地监测纤维蛋白血栓形成和纤溶的两侧，并提供一种易于使用的检测方法，有助于在常规临床实践中阐明出血性疾病的潜在发病机制。
