Analysis on the etiology and patho-physiology of neonatal thrombosis and the development of their therapy

从该基金会支持的日本全国新生儿血栓形成调查来看，日本新生儿血栓形成的频率比西方国家低十分之一。但是，这项调查是回顾性的，诊断标准不完全确定。因此，尚不清楚这种差异是由于种族还是诊断技能造成的。然而，本调查新生儿血栓形成的病因和病理生理学与西方国家的报道相似。日本新生儿血栓的治疗多为保守治疗，但与成人病例一样，部分病例也采用纤溶治疗，如u-PA或t-PA。但是，纤维蛋白溶解治疗的剂量和时间还不确定，需要在不久的将来确定。在本调查中，遗传因素的发生率很低。但根据我们的经验，血浆中蛋白C或另一种抗血栓因子的水平与同龄的对照组相比非常低。随着生长，这些因素逐渐达到控制值。因此，遗传因素不可否认，但抗血栓因子低似乎是新生儿血栓形成的危险因素之一。目前，对新生儿血浆凝血因子和纤溶因子水平的研究较多，但近年来的研究和我们的研究表明，从生理角度评价新生儿凝血因子和纤溶因子在包括血小板在内的全血环境中的水平很重要。当时认为，少量凝血酶、ADP等血小板活化因子对凝血有夸大作用，因此，调控这些血小板活化因子对了解新生儿体内稳态及血栓形成具有重要意义。从研究开发的用于治疗血友病抑制剂患者出血的活化VII （VIIa）途径来看，VIIa途径在生理性止血机制中起重要作用，Vila在少量血小板中诱导有效的内稳态。揭示生理止血调节系统也是必要的。采用免疫学方法建立凝血酶活化抑制因子（TAFI），并继续测定新生儿在不同病理生理条件下的血浆水平。我们揭示了新生儿体内平衡的一些生理学意义，并继续研究。最后，我们将揭示新生儿血栓形成的危险因素，建立诊断标准，并在不久的将来进行前瞻性研究。少

From the nation-wide survey of neonatal thrombosis in Japan supported by this foundation, the frequency of neonatal thrombosis in Japan was one-tenth lower than that of western countries. But, this survey was retrospective, and the diagnostic criteria were not fully assured. Therefore, it is unclear whether the difference is due to the race or the diagnostic skill. However, the etiology and patho-physiology of neonatal thrombosis from this survey were similar to those of the reports from western countries. The therapy of neonatal thrombosis in Japan was mostly conservative, but the fibrinolytic therapy, such as u-PA or t-PA, was used in some cases as in adult cases. But, the doses and the timing of the fibrinolytic therapy were not assured and then it needs to establish it near future. In this survey, the incidence of the genetic factors was very low. But in our experience, the plasma levels of protein C or another anti-thrombotic factor were very low comparing with the matched-aged-co … More ntrol values. And these factors gradually reached to the control values with the growth. Therefore, the genetic factor is not to be denied but it seems that the low anti-thrombotic factor is one of the risk factors in neonatal thrombosis.Until now, the plasma levels of the coagulation and fibrinolytic factors in newborn are intensively investigated, but the recent researches and our studies demonstrate that it is important to evaluate it in the whole blood milieu included the platelets from the physiological perspective. At that time, it was suggested that the platelet-activation factors, such as small amount of thrombin and ADP exaggerated the coagulation, then, it is important to regulate these platelet-activation factors for the understanding the homeostasis and thrombosis in the newborn. From the study on the activated VII (VIIa) developed for the treatment of the bleedings in patients with hemophilia inhibiter, The VIIa pathway is important to physiologic haemostatic mechanism and Vila induced the effective homeostasis even in a few amount of platelets.It is also necessary to reveal the physiological haemostatic regulatory system. Thrombin activatable inhibitory factor (TAFI) was established by the immunological method, we continued the measurement of plasma levels in newborn at several patho-physiological conditions. We revealed the some physiological significance in the newborn homeostasis and continued the study.Finally, we will reveal the risk factors of neonatal thrombosis and establish the diagnostic criteria, and perform the prospective study near future. Less