Ishihara Takashi, Nogami Keiji, Onishi Tomoko, Ogiwara Kenichi, Ochi Satoshi, Yamazaki Masaharu, Shima Midori
Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Central Clinical Laboratory, Nara Medical University, Kashihara, Nara, Japan.
Pediatr Int. 2019 Sep;61(9):872-881. doi: 10.1111/ped.13919.
Global hemostatic mechanism(s) in patients with disseminated intravascular coagulation (DIC) are poorly understood. There are few diagnostic criteria of DIC based on overall or global hemostatic mechanisms.
We have assessed in detailed the dynamic global hemostatic changes using thrombin and plasmin generation assay (T/P-GA), clot fibrinolytic waveform analysis (CFWA) and not-activated rotational thromboelastometry (NATEM), in a young girl with DIC associated with acute myeloid leukemia (AML). The ratios of endogenous thrombin potential (T-EP) and plasmin lag time (P-LT) relative to normal plasma was sourced from pooled normal plasma from healthy volunteers on T/P-GA.
The inverse P-LT ratio prior to tranexamic acid (TXA) treatment was greater than the T-EP ratio (1.1-2.8 and 0.83-1.2, respectively). Significant reduction in inverse P-LT ratio (0.084-1.3) was observed after TXA treatment. The interval from clotting to the initiation of fibrinolysis (fibrinolysis lag time: FLT) in CFWA was significantly shorter than the control at onset (74.2-91.6 s vs 109 s), indicating enhanced fibrinolysis. Data from an adult with acute promyelocytic leukemia-associated DIC also supportively showed a high inverse P-LT ratio (2.1) and shortened FLT (83.7 s). The clotting time in patient whole blood using NATEM-mode during an episode of severe epistaxis markedly shortened beyond control, but returned to normal after the addition of an anti-tissue factor (TF) monoclonal antibody.
The release of intravascular TF contributed to sustained activation of coagulation and subsequent fibrinolytic activity in this patient with AML-associated DIC, and T/P-GA could provide better quantitative data than conventional assays in these circumstances.
弥散性血管内凝血(DIC)患者的整体止血机制尚不清楚。基于整体或全局止血机制的DIC诊断标准很少。
我们使用凝血酶和纤溶酶生成试验(T/P-GA)、凝块纤维蛋白溶解波形分析(CFWA)和未激活旋转血栓弹力图(NATEM),详细评估了一名患有与急性髓系白血病(AML)相关的DIC的年轻女孩的动态全局止血变化。内源性凝血酶潜力(T-EP)和纤溶酶延迟时间(P-LT)相对于正常血浆的比率来自T/P-GA中健康志愿者的混合正常血浆。
氨甲环酸(TXA)治疗前P-LT反比大于T-EP比率(分别为1.1 - 2.8和0.83 - 1.2)。TXA治疗后观察到P-LT反比显著降低(0.084 - 1.3)。CFWA中从凝血到纤溶开始的间隔时间(纤溶延迟时间:FLT)在发病时明显短于对照组(74.2 - 91.6秒对109秒),表明纤溶增强。一名患有急性早幼粒细胞白血病相关DIC的成年人的数据也支持性地显示出高P-LT反比(2.1)和缩短的FLT(83.7秒)。在严重鼻出血发作期间,使用NATEM模式测量患者全血的凝血时间明显短于对照组,但在添加抗组织因子(TF)单克隆抗体后恢复正常。
血管内TF的释放导致该AML相关DIC患者的凝血持续激活和随后的纤溶活性,在这些情况下,T/P-GA比传统检测方法能提供更好的定量数据。