Comparative study of the prevalence of clotting factor deficiency in carriers of haemophilia A and haemophilia B

Boban, Ana; Lambert, Catherine; Lannoy, Nathalie; Hermans, Cédric

doi:10.1111/hae.13298

Cited by 10 publications

(12 citation statements)

References 9 publications

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“…Apart isolated cases of girls, only one publication includes a substantial number of Amish girls, carriers of haemophilia B with a median age of 18 years (range 1‐70 years) 4 . Indeed, the available literature on carriers includes a majority of adults 1,3,9,10 …”

Section: Women and Girls With Haemophilia: Importance Of Early Diagnosismentioning

confidence: 99%

Women and girls with haemophilia: Lessons learned

2020

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Severe and moderate factor VIII (FVIII) or IX (FIX) deficiencies in female carriers of haemophilia are rarely observed, but mild deficiency is quite frequent, although insufficiently recognized and registered. The confusion between the genetic diagnosis of the carriership, mainly assessed at adult age and the diagnosis of the bleeding disorder for those who have low factor levels often prevents early diagnosis of a potential bleeding risk. The factor levels in obligate or potential carriers of haemophilia can be assessed during childhood, possibly apart from genetic assays. The absence of early recognition of the bleeding disorder precludes the anticipation of menarche and the prevention of potential heavy menstrual bleeding to heavy menstrual bleeding. Standardized bleeding assessment tools (BAT) have demonstrated that women and girls with haemophilia (WGWH) have increased bleeding scores as compared to the general female population, however weakly correlating with factor levels. More recent evidence has highlighted that hemarthroses affect 4% to 19% of carriers and that some of them could experience sub‐clinical joint bleeding. Desmopressin for women with FVIII deficiency and abnormal ISTH‐BAT scores had a significantly lower FVIII response to DDAVP compared to those with normal bleeding scores, which could at least partially explain more postsurgical bleeding. Management of delivery of haemophilia carriers requires attention to the risks of maternal bleeding, the risks of foetal bleeding, preconception and prenatal care, strategies to reduce maternal bleeding, choice of mode of delivery to reduce foetal/neonatal bleeding, and postpartum care. Either prior to pregnancy, or during early pregnancy, a plan should be developed that addresses the needs of both the mother and her unborn baby. If the unborn baby is a male proven to be or potentially affected by moderate or severe form of haemophilia, there is a risk of severe foetal bleeding, so a planned caesarean delivery may be preferred. If the unborn baby is a carrier, or potentially affected carrier, there is still the risk of non‐severe bleeding so invasive foetal procedures and operative vaginal delivery (forceps or vacuum) should be avoided. Further studies based on large cohorts will help the community to favour earlier diagnosis, increase knowledge on WGWH and promote better care.

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Section: Women and Girls With Haemophilia: Importance Of Early Diagnosismentioning

confidence: 99%

Women and girls with haemophilia: Lessons learned

2020

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“…The impact of living with these signs and symptoms is associated with impaired quality of life scores for pain and general health compared with unaffected controls [23] . If they were men, many would be diagnosed as having mild, moderate and even severe haemophilia [24,25] .…”

Section: Why Is 'Carrier' a Negative Term For Women With Haemophilia?mentioning

confidence: 99%

“You’re only a carrier” – women and the language of haemophilia

Chaplin¹,

Khair²

2021

The Journal of Haemophilia Practice

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Women who have the gene variant for haemophilia are labelled solely as ‘carriers’ unless they have a factor VIII activity of ≤40%. This term, which describes an individual who can pass on a disorder but are themselves unaffected, reflects a legacy that extends from the 18th century to the present day. There is strong evidence that women labelled as carriers experience heavy periods, joint damage, pain and impaired quality of life. The label ‘carrier’ does not recognise this burden and is associated with guilt, stigma and difficulty accessing care. People living with a long-term disorder should now be described using person-first terminology and it is common to see the term ‘people with haemophilia’. The term ‘carrier’ should be limited to its application in genetics and not used as a catch-all label for women with haemophilia.

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“…Of the 244 haemophilia carriers identified at our centre from 2001 to 2019, 215 are carriers of haemophilia A and 29 of haemophilia B, with a coagulant factor level between 1 and 110 IU/dL. Among these women, we selected female carriers with a level of FVIII and FIX between 1 and 50 IU/dL, who made up 30% (73/246) of the female carriers referred to our centre [13,14]. World Federation of Hemophilia (WFH) guidelines classify female carriers with clotting factor levels of ≤50 IU/dL as having haemophilia [15].…”

Section: Subjectsmentioning

confidence: 99%

X Chromosome inactivation: a modifier of factor VIII and IX plasma levels and bleeding phenotype in Haemophilia carriers

et al. 2020

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Haemophilia A and B are X-linked hemorrhagic disorders caused by gene variants in the F8 and F9 genes. Due to recessive inheritance, males are affected, while female carriers are usually asymptomatic with a wide range of factor VIII (FVIII) or IX (FIX) levels. Bleeding tendency in female carriers is extremely variable and may be associated with low clotting factor levels. This could be explained by F8 or F9 genetic variations, numerical or structural X chromosomal anomalies, or epigenetic variations such as irregular X chromosome inactivation (XCI). The aim of the study was to determine whether low FVIII or FIX coagulant activity in haemophilia carriers could be related to XCI and bleeding symptoms. HUMARA assay was performed on 73 symptomatic carriers with low clotting activity ≤50 IU/dL. Bleeding Assessment Tool (BAT) from the International Society on Thrombosis and Haemostasis (ISTH) was used to describe symptoms in the cohort of carriers. In 97% of haemophilia carriers, a specific gene variant in heterozygous state was found, which alone could not justify their low FVIII or FIX levels (≤50 IU/dL). A statistical association between XCI pattern and FVIII and FIX levels was observed. Moreover, female carriers with low coagulant activity (≤20 IU/dL) and high degree of XCI ( ≥ 80:20) had a higher ISTH-BAT score than the carriers with the opposite conditions (>20 IU/dL and <80:20). In our cohort of haemophilia carriers, XCI was significantly skewed, which may contribute to the low expression of clotting factor levels and bleeding symptoms.

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Comparative study of the prevalence of clotting factor deficiency in carriers of haemophilia A and haemophilia B

Cited by 10 publications

References 9 publications

Women and girls with haemophilia: Lessons learned

Women and girls with haemophilia: Lessons learned

“You’re only a carrier” – women and the language of haemophilia

X Chromosome inactivation: a modifier of factor VIII and IX plasma levels and bleeding phenotype in Haemophilia carriers

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