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新生儿血小板减少症:在血小板计数减少的情况下凝血酶的生成和 rFVIIa 在脐血中的作用。

Neonatal thrombocytopenia: Thrombin generation in presence of reduced platelet counts and effects of rFVIIa in cord blood.

机构信息

Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.

出版信息

Sci Rep. 2019 May 29;9(1):8014. doi: 10.1038/s41598-019-44199-y.

Abstract

Healthy neonates exhibit a well-functioning haemostatic system despite peculiarities regarding composition of clotting factors and inhibitors as well as impaired platelet aggregation. Thrombocytopenia and severe bleeding events are feared in sick infants. Recombinant factor VIIa (rFVIIa) is a haemostatic agent used as a last resort in neonates with refractory bleedings. Aim of this study was to investigate in-vitro (i) changes in thrombin generation with different platelet counts, (ii) effects of rFVIIa under conditions of thrombocytopenia and (iii) potentially differing dose-response of rFVIIa in cord blood as a surrogate for neonatal blood compared to adult blood. Thrombin generation parameters were observed in cord blood plasma and adult plasma with various platelet counts, with or without addition of rFVIIa, respectively. Low platelet counts did not influence thrombin generation in cord blood in contrast to adult blood. RFVIIa primarily affected lag time throughout all platelet concentrations. Interestingly, peak height was reduced exclusively in cord blood plasma after addition of rFVIIa. No significant differences regarding dose-response were observed between cord blood and adult blood. In contrast to adult blood, thrombocytopenia in cord blood does not significantly influence thrombin generation. Even at very low platelet counts there is enough negatively charged surface to support rFVIIa action in plasma from cord blood and adult blood in-vitro.

摘要

健康的新生儿尽管存在凝血因子和抑制剂组成的特殊性以及血小板聚集受损等特点,但仍表现出功能良好的止血系统。患有疾病的婴儿会出现血小板减少症和严重出血事件。重组凝血因子 VIIa(rFVIIa)是一种止血剂,在难治性出血的新生儿中被用作最后的手段。本研究的目的是在体外(i)研究不同血小板计数下凝血酶生成的变化,(ii)rFVIIa 在血小板减少症情况下的作用,以及(iii)与成人血液相比,脐带血中 rFVIIa 的潜在不同剂量反应作为新生儿血液的替代物。在分别含有或不含有 rFVIIa 的情况下,观察了脐带血血浆和成人血浆中不同血小板计数下的凝血酶生成参数。与成人血液相比,低血小板计数不会影响脐带血中的凝血酶生成。rFVIIa 主要影响所有血小板浓度下的延迟时间。有趣的是,添加 rFVIIa 后仅降低了脐带血血浆中的峰高。在脐带血和成人血之间没有观察到关于剂量反应的显著差异。与成人血相比,脐带血中的血小板减少症并不会显著影响凝血酶生成。即使血小板计数非常低,也有足够的负电荷表面在体外支持 rFVIIa 在脐带血和成人血血浆中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d35/6541708/8e7bb9a445f9/41598_2019_44199_Fig1_HTML.jpg

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