Cerebral vasculature exhibits dose-dependent sensitivity to thrombocytopenia that is limited to fetal/neonatal life

• Published in: Blood Vol. 139; no. 15; pp. 2355 - 2360
• Main Authors: Farley, Alison M., Dayton, Merle, Biben, Christine, Stonehouse, Olivia, Terreaux, Antoine, Taoudi, Samir
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.04.2022
• Subjects: Animals; Antigens, Human Platelet; Cerebral Hemorrhage; Female; Fetus; Humans; Mice; Pregnancy; Prenatal Care; Thrombocytopenia, Neonatal Alloimmune
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2021014094

Whether increasing platelet counts in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is effective at preventing intracerebral hemorrhage (ICH) has been a subject of debate. The crux of the matter 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 ICH 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 the normal platelet number, and that ICH becomes fully penetrant below 10% of the normal platelet number. We also demonstrate that although the neonatal mouse is susceptible to thrombocytopenia-induced ICH, this sensitivity is rapidly lost between postnatal days 7 and 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. •Severity of ICH is linked to the severity of in utero thrombocytopenia.•Resilience of the cerebral vasculature to thrombocytopenia occurs within the first 2 weeks of birth. [Display omitted]