Patho-physiological analysis for the mechanism of neonatal haemostatic and neonatal thrombosis, and exploration of the new therapeutic approach

我们研究了以下主题，以了解新生儿止血和血栓形成的病理生理学，如Grand-in-Aid用于科学研究的应用中所述。首先，我们对新生儿DIC进行了回顾性研究，并检查了市售抗蛋白酶肽的有效性。第二部分，我们用新生儿血液中加入少量凝血酶或ADP、重组活化因子VII（FYIIa），通过血栓弹力图研究新生儿血液的止血机制。并应用血栓弹力图检测抗凝血酶、活化蛋白C、血栓调节蛋白、抗栓肽等抗血栓药物的作用。此外，我们分析了重组活化因子VII的止血机制，使用几种凝血因子缺陷血浆和人工，减少血小板血。进一步了解了FVIIa的止血机制，发现血小板是FVIIa止血的关键因素之一。第三，我们研究了脐带血中的外膜ATP酶活性，发现它对新生儿止血的抗血栓作用是重要的。第四，验证了从早产儿到足月儿脐带血中血管性血友病因子裂解蛋白酶的活性。并在剪应力条件下，应用脐带血进行抗血栓新生儿中心静脉导管的研究。

We studied the following subjects for the pathophysiological understanding of the neonatal haemostasis and thrombosis as described in the application of Grand-in-Aid for scientific research. The first, we performed a retrospective study on neonatal DIC and also examined into the effectiveness of commercial available anti-protease peptides. The second, we studied the haemostatic mechanism in neonate by thrombelastogragh, using adult bloods mixed with a very small amount of thrombin or ADP, recombinant activated factor VII (FYIIa). And we examined the effect of several kinds of anti-thrombotic drugs, such as antithrombin, activated protein C, thrombomodulin, anti-thrombotic peptides using thrombelastograph. Furthermore, we analysed the haemostatic mechanism of recombinant activated factor VII using several kinds of coagulation factor-deficient plasmas and artificial, reduced platelet blood. And we understood the haemostatic mechanism of FVIIa and also found that platelets were one of key factors for haemostasis induced by FVIIa. The third, we studied a ecto-ATPase activity in umbilical cord bloods and found that it was important for anti-thrombotic effects on neonatal haemostasis. The fourth, we verified the activity of von Willebrand factor cleaving protease in cord bloods from premature to mature babies. And we studied on anti thrombotic neonatal central catheter using cord bloods under shear stress condition.