Cerebral vasculature exhibits dose-dependent sensitivity to thrombocytopenia that is limited to fetal/neonatal life
- Author(s)
- Farley, A; Dayton, M; Biben, C; Stonehouse, O; Terreaux, AF; Taoudi, S;
- Journal Title
- Blood
- Publication Type
- epub ahead of print
- Abstract
- Whether increasing platelet counts in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is effective at preventing intra-cerebral hemorrhage (ICH) has been a subject of debate. The crux has been whether thrombocytopenia is the major driver of ICH in diseases such as FNAIT. We recently demonstrated in mice that severe thrombocytopenia was sufficient to drive intra-cerebral hemorrhage in utero and in early neonatal life. It remains unclear what degree of thrombocytopenia is required to drive ICH and for how long after birth thrombocytopenia can cause ICH. By inducing a thrombocytopenic range, we demonstrate that there is a large buffer-zone of mild thrombocytopenia that does not result in ICH, that ICH becomes probabilistic at 40% of normal platelet numbers, and that ICH becomes fully penetrant below 10% of normal platelet number. We also demonstrate that although the neonatal mouse is susceptible to thrombocytopenia-induced ICH, this sensitivity is rapidly lost between post-natal days 7 - 14. These findings provide important insights into the risk of in utero ICH with varying degrees of thrombocytopenia and into defining the developmental high-risk period for thrombocytopenia-driven ICH in a mouse model of FNAIT.
- Publisher
- ASH
- Research Division(s)
- Epigenetics And Development
- PubMed ID
- 35148538/
- Publisher's Version
- https://doi.org/10.1182/blood.2021014094
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-02-18 11:34:19
Last Modified: 2022-02-18 03:10:31