Prenatal diagnosis in rare bleeding disorders-An unresolved issue?

Area of Science:

• Medical Genetics
• Hematology
• Obstetrics

Background:

• Intracranial hemorrhage (ICH) is a major cause of mortality in rare bleeding disorders (RBD).
• Prenatal diagnosis (PND) offers a lifesaving preventative strategy for affected pregnancies.
• PND is frequently requested for factor XIII and factor VII deficiencies.

Purpose of the Study:

• To review the literature on PND for rare bleeding disorders.
• To highlight the role of PND in managing and preventing ICH in fetuses with RBD.
• To analyze the outcomes of pregnancies undergoing PND for RBD.

Main Methods:

• Literature search of PubMed, EMBASE, SCOPUS, and Web of Science databases for PND in RBD.
• Analysis of reported PND cases, focusing on identified factor deficiencies and ICH occurrence.
• Review of molecular methods (direct sequencing, linkage analysis, PCR-RFLP) and factor assays used for PND.

Main Results:

• 39 PND cases for RBD were identified, predominantly for factor XIII and VII deficiencies.
• Seven severely affected fetuses were detected: 3 with FXIII, 3 with FVII, and 1 with FX deficiency.
• Intrauterine ICH occurred in one FXIII deficiency case; one FVII deficiency case received intrauterine transfusion; one post-delivery ICH was reported.

Conclusions:

• PND is essential for identifying fetuses at risk of ICH due to rare bleeding disorders.
• Early detection through PND allows for timely interventions, such as intrauterine transfusions.
• PND plays a vital role in reducing ICH-related morbidity and mortality in rare bleeding disorders.