A cross‐sectional study of bleeding phenotype in haemophilia A carriers

Abstract

Summary Haemophilia A carriers have historically been thought to demonstrate normal haemostasis. However, recent data demonstrates that despite normal factor VIII, haemophilia A carriers demonstrate an increased bleeding tendency. We tested the hypothesis that obligate haemophilia carriers demonstrate an increase in bleeding symptoms. A cross sectional study was performed comparing haemophilia A carriers to normal women. Questionnaire assessment included a general bleeding questionnaire, condensed MCMDM-1VWD bleeding assessment tool and Pictorial Bleeding Assessment Chart (PBAC). Laboratory assessment included complete blood count, prothrombin time, activated partial thromboplastin time, fibrinogen activity, FVIII activity (FVIII:C), von Willebrand factor antigen level, ristocetin cofactor, platelet function analyser-100™ and ABO blood type. 44 haemophilia A carriers and 43 controls were included. Demographic features were similar. Laboratory results demonstrated a statistically significant difference only in FVIII:C (82.5 versus 134%, p value < 0.001). Carriers reported a higher number of bleeding events, and both condensed MCMDM-1 VWD bleeding scores (5 versus 1, p value < 0.001) and PBAC scores (423 versus 182.5, p value = 0.018) were significantly higher in carriers. Haemophilia A carriers exhibit increased bleeding symptoms when compared to normal women. Further studies are necessary to fully understand the bleeding phenotype in this population and optimize clinical management.

Can we compare haemophilia carriers with clotting factor deficiency to male patients with mild haemophilia?

“…10 This delay could be due to several reasons: first, an undervaluation of the personal and family haemorrhagic history by patients and/or physicians 5 ; second, the lack of awareness of haemophilia in the differential diagnosis of females presenting with haemorrhagic diathesis. However, a major difference in the frequency of haemarthrosis was observed, which contrasts with previously published data 7,16 Differences in cohort size and study methodology might partially explain this discrepancy. This difference, however, cannot be explained by a different haemorrhagic tendency, because postmedical intervention haemorrhages were reported in a similar proportion in the two groups.…”

“…11,12 WGH represent the second largest group of women with inherited blood clotting defects after patients with von Willebrand disease (VWD). 6,7,14 Despite the fact that the haemorrhagic phenotype of WGH with reduced clotting factor activity has been reported in literature to resemble that of mild haemophilia patients and that the recommended treatment is the same, 2 to our knowledge, this was the first study that directly compared WGMH and males with mild haemophilia. 6,7,14 Despite the fact that the haemorrhagic phenotype of WGH with reduced clotting factor activity has been reported in literature to resemble that of mild haemophilia patients and that the recommended treatment is the same, 2 to our knowledge, this was the first study that directly compared WGMH and males with mild haemophilia.…”

Bleeding assessment in haemophilia carriers—High rates of bleeding after surgical abortion and intrauterine device placement: A multicentre study in China

“…15 Second, genotype analysis was not performed in this population of obligate carriers. First, we did not perform tests for von Willebrand factor (VWF) levels and ABO blood type that might modulate the factor levels or bleeding phenotype.…”

The national blueprint for pregnancy/birth longitudinal cohorts to study factor VIII immunogenicity: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors

“…Prenatal genotype can inform risk for inhibitors . Carriers overall have lower coagulation factor levels and bleed more than other women, and therefore should be patients. At HTCs, 7%‐12% of haemophilia patients are female .…”