Bleeding Disorders Across the Female Reproductive Lifespan: From Adolescence to Adulthood

Women with inherited bleeding disorders experience a different bleeding phenotype than men due to vaginal bleeding. In most women, heavy menstrual bleeding is the first symptom of a bleeding disorder. Improper diagnostic and therapeutic management can lead to unnecessary interventions and an increased risk for severe bleeding during hemostatic challenges. In this thesis we focus on the diagnostic and therapeutic management of menstruating adolescents without a diagnosed bleeding disorder and in adult women with an inherited bleeding disorder that experience vaginal bleeding.
Heavy menstrual bleeding in adolescents
Heavy menstrual bleeding is reported by over 30% of adolescents and is often caused by immaturity of the hypophyseal-pituitary-gonadal axis. However, it can also be caused by an inherited bleeding disorder. Several screening and quantification tools for heavy menstrual bleeding, and bleeding phenotype have been developed. These tools are however validated in people that visited a clinic with a bleeding phenotype. To determine the role of these tools in the diagnostic workup for adolescents with heavy menstrual bleeding, it is first necessary to assess their outcomes in the general menstruating population. The results of this study are shown in Chapter 2.
In Chapter 3 we investigated how often adolescents visit their general practitioner with complaints of heavy menstrual bleeding. Additionally, we gather data on the diagnostic and therapeutic workup of the general practitioner. We revealed that less than 8 adolescents per 1000 person years consulted their general practitioner and if they did, most of them received a hormonal oral contraceptive pill without extensive laboratory testing. In Chapter 4 we observed that there was no difference in von Willebrand factor and factor VIII levels between menstrual phases in women with heavy menstrual bleeding, indicating that blood sampling for a bleeding disorder diagnosis can be done irrespective of the menstrual cycle.

Peripartum management in women with von Willebrand Disease and haemophilia carriers
Once pregnant, women with von Willebrand disease (VWD) and haemophilia carriers have an increased risk for postpartum haemorrhage. Clotting factor prophylaxis is given to those with low third trimester activity levels with the aim to minimize this risk. In Chapter 5 and 6 we learned that increasing the third trimester cut-off for prophylaxis from 50 IU/dL to 80 IU/dL, and increasing peak target levels at delivery from 100 IU/dL to 150 IU/dL did not decrease the risk for severe postpartum haemorrhage in women with VWD and haemophilia carriers.
To understand these findings, we wanted to know more about the obstetric time trends in the general Dutch obstetric population within the same time frame of the PRIDES study (Chapter 5 and 6) and a predecessor study. In Chapter 7 we observed a high severe postpartum haemorrhage incidence in women with an inherited bleeding disorder the first two years after implementation of the revised guideline, together with an increase of caesarean sections, partially explaining the absence of effect of the revised guideline.
The impact of the guideline and postpartum haemorrhage on quality of life and childbirth satisfaction was investigated in Chapter 8. Here we found an overall high quality of life, with a slower recovery at six weeks postpartum compared to an historic cohort of women without a bleeding disorder. Childbirth satisfaction was significantly higher in women with a bleeding disorder. Childbirth experience was comparable, with the exception that haemophilia carriers had more worries about their child during childbirth.