133 General discussion and future perspectives What are intraoperative strategies to reduce intraoperative bleeding and what are patient preferences regarding surgical interventions for HMB in women with bleeding disorders? The ‘European principles of care for women and girls with bleeding disorders’ report published by the European Haemophilia Consortium (EHC) and the European Association for Haemophilia and Allied Disorders (EAHAD), contains 10 recommendations to address the needs of women with bleeding disorders. These recommendations outline the breadth of care that all patients with bleeding disorders should have access to throughout their lives, and cover clinical, quality of life, education, and research domains [13]. Among the recommendations is to provide ‘early recognition and optimal management of HMB’ [13]. To investigate this, we conducted a literature review and a focus group study among women with von Willebrand disease. We performed a systematic review of literature to determine which surgical route is optimal for women with diagnosed von Willebrand disease (VWD) and HMB (Chapter 2). The existing global literature on prophylactic and therapeutic strategies for intraoperative bleeding in women with VWD and HMB primarily comes from small cohort studies. While many gynecological studies describe strategies for managing intraoperative bleeding during hysterectomy or endometrial ablation in women with severe menstruation, they often do not specify whether the cohorts include women with impaired coagulation. However, HMB is mostly the first symptom of a bleeding tendency and various bleeding disorders [4] [1],[5]. Additionally, VWD type 1 is one of the most common inherited bleeding disorders with a prevalence ranging from 5%-24% in women with HMB [3]. So, to increase awareness of bleeding disorders among gynaecologists and in gynaecological clinical research it is advisable to specifically describe and investigate women with bleeding disorders within HMB cohorts. To reduce diagnostic delay in bleeding disorders, adequate and timely specialist testing should be included in the work up for women at risk. In chapter 3 we discuss the high prevalence of reduced thrombin generation and/or decreased platelet response in women with unexplained HMB. In our explorative single-center population-based study, we show a high prevalence of impaired platelet function (24%) and a similar high prevalence of reduced thrombin generation lag time (29%) in women with HMB, as measured with a novel high-precision testing strategy. In contrast to the high prevalence of women with impaired platelet function and coagulation, the number of patients with reduced VWF responsiveness (found in only two women (3,4%)) was less frequent than expected. One can argue whether our small patient population in this explorative study allows us to give any recommendations for gynaecologists or GP. Nevertheless, hundreds of girls and women with HMB and anemia are referred to outpatient OB-GYN clinics each year with variable inpatient hematologic evaluation and management. Future OB-GYN guidelines should emphasize the early identification of at-risk patients in the HMB population and promote effective communication and implementation strategies to reduce the burden of this preventable complication [14]. 8
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