Postmortem diagnosis of severe factor X deficiency in a fetus with intracranial hemorrhage resulting in intrauterine death

• Published in: Journal of thrombosis and haemostasis : JTH 2023, Vol.21 (12), p.3501-3507
• Main Authors: Krumb, Evelien, Mehta, Nishita, Hutchinson, Ciaran, Jradeh, Bilal, Jaslowska, Ewa, Gomez, Keith, Abdul-Kadir, Rezan
• Format: Report
• Language: English
• ISSN: 1538-7836
• DOI: 10.1016/j.jtha.2023.08.027

In patients with severe congenital factor X deficiency, spontaneous intracranial hemorrhage (ICH) is particularly frequent in early childhood. We describe a case of fetal death at 26 weeks due to massive ICH. Gene panel analysis of postmortem samples revealed homozygosity for a pathologic F10 gene variant (c.1210T>C, p.Cys404Arg), which impedes correct folding of the catalytic serine protease domain and, therefore, causes a significant reduction in FX levels. The parents, not consanguineous but of the same ethnic community, were found to be heterozygous for this variant and did not have any personal or family history of abnormal bleeding. To the best of our knowledge, this is the first reported case of severe FX deficiency resulting in ICH diagnosed through postmortem genetic analysis. It illustrates the importance of exploring the etiology of fetal or neonatal ICH, which may impact future pregnancies, and the treatment of a potential coagulopathy in the child.