The effect of carriers’ reproductive choices and pregnancy history on sporadic severe haemophilia: A 20‐year retrospective study through a regional registry

Abstract

Introduction Haemophilias are X‐linked inherited bleeding disorders, due to de novo F8/F9 gene variants in 30–50% of cases. The identification of causative variant in index cases (IC) is crucial for genetic counselling in related women. Over the last 20 years the Emilia‐Romagna Regional Haemophilia Registry documented high proportions of sporadic severe haemophilia. Aim To clarify if carriers’ reproductive choices influence the sporadic/familial ratio of severe haemophilia. Methods Genetic counselling and genotyping in 221 relatives of severe IC were retrospectively reviewed, retrieving reproductive choices and pregnancy history of childbearing‐age carriers from familial and sporadic pedigrees and according to the IC degree of relationship (mothers, daughters, II/other). Results Carriers’ identification rates were lower in sporadic women and in other‐degree relatives. Among childbearing age women (n = 140), carriers were 37/48 (77%) and 57/92 (62%) of familial and sporadic relatives, respectively. Forty‐five/57 sporadic carriers experienced 67 pregnancies, while 21/37 familial carriers had 39 pregnancies (four voluntary terminations), with a significantly higher number of affected sons in the former (40/67 vs. 12/35, P = .025). Prenatal diagnosis was chosen by 40% and 47% of sporadic and familial aware carriers, respectively. Sporadic mothers often avoided further pregnancies (17/38, 45%) after a firstborn affected child, while familial mothers tended to face pregnancies without prenatal approaches (6/10, 60%). Conclusion In this cohort sporadic offspring account for more than 70% of severe haemophilia cases. This increasing proportion is likely to reflect the influence in reproductive choices of awareness of carriers’ status, particularly in sporadic mothers, and of prenatal diagnosis options.

The psychosocial impact of haemophilia from patients’ and caregivers’ point of view: The results of an Italian survey

“…Such an intervention is important for the emotional wellbeing of patients and their caregivers, not only at the moment of diagnosis disclosure but through the entire life cycle. 36,37 In particular, mental health support aims to avoid the rejection of haemophilia, like fear of reporting bleedings and non-compliance, 3,38,39 improving health state and quality of life. A high number of programs to provide emotional support was proposed by different health professionals, however the lack of awarenees on psychosocial care and high heterogeneity of the available literature does not allow to determine the best approaches to the comprehensive patient care.…”

“…In the challenging phase of the diagnosis communications most respondents report that they did not receive psychological support. Such an intervention is important for the emotional wellbeing of patients and their caregivers, not only at the moment of diagnosis disclosure but through the entire life cycle 36,37 . In particular, mental health support aims to avoid the rejection of haemophilia, like fear of reporting bleedings and non‐compliance, 3,38,39 improving health state and quality of life.…”

Prevalence of sporadic haemophilia A

“…The authors concluded that these different reproductive choices of sporadic and carrier mothers influence the increasing proportion of sporadic descendants found. 9 The increased frequency of sporadic hemophilia A may have an impact on future public health care policies for this population. Sporadic cases are more difficult to diagnose because there is no family history of the disease.…”

“…The reproductive choices of women known to be carriers influence the proportion of severe sporadic and familial haemophilia A. 9 Riccardi et al showed that the prenatal diagnosis of haemophilia was chosen by 40% of sporadic mothers and by 47% of carrier mothers.…”