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Background: Heavy menstrual bleeding (HMB) is associated with a reduced quality of life and limitations in social and physical functioning. Data on HMB in women with rare bleeding disorders (RBDs), including coagulation factor deficiencies and fibrinolytic disorders, are scarce., Objectives: To analyze the prevalence, severity, and treatment of HMB in Dutch women with an RBD., Methods: The Rare Bleeding Disorders in the Netherlands (RBiN) study included 263 patients with an RBD from all 6 hemophilia treatment centers (October 2017-November 2019). In this analysis, data of 111 women aged ≥16 years were studied. According to the International Society on Thrombosis and Haemostasis bleeding assessment tool, HMB symptoms were scored from 0 (no/trivial) to 4 (severe symptoms requiring medical intervention). HMB was defined as a score ≥1. Age at RBD diagnosis was extracted from patient files., Results: HMB was reported by 80% of women (89/111) and was more prevalent in women with a fibrinolytic disorder (33/35; 94%) than in women with a coagulation factor deficiency (56/76; 74%) (P = .011). Of the 89 women with HMB, 82% (n = 73) ever required treatment. Multiple treatment modalities were frequently used, both in severe and mild deficiencies. Hormonal treatment was mostly used (n = 64; 88%), while antifibrinolytics were prescribed less frequently (n = 18; 25%). In women with HMB since menarche (n = 61; 69%), median age at RBD diagnosis was 28 years (IQR, 14-41)., Conclusion: HMB is common in women with RBDs. Women with mild deficiencies also frequently reported HMB. Only a minority of women were treated with hemostatic agents. A significant diagnostic delay was observed after the onset of HMB symptoms., Competing Interests: Declaration of competing interests K. Meijer reports speaker fees from Bayer and Alexion, participation in trial steering committee for Bayer, consulting fees from Uniqure, participation in data monitoring and endpoint adjudication committee for Octapharma. M.H. Cnossen's institution has received investigator-initiated research and travel grants as well as speaker fees over the years from the Netherlands Organisation for Scientific Research (NWO) and Netherlands National research Agenda (NWA), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch Innovatiefonds Zorgverzekeraars, Stichting Haemophilia, Baxter/Baxalta/Shire/ Takeda, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, Roche, and Nordic Pharma, and for serving as a steering board member for Roche, Bayer and Novartis. All grants and fees go to the Erasmus MC as an institution. She is coordinator of Erasmus MC as a Health Care Provider within the European Reference Network (ERN) for rare hematological diseases EuroBloodNet and (co)leader of the local Erasmus MC Expert Centers for Rare Bleeding Disorders and Sickle Cell and Thalassemia Comprehensive Care Center. R.E.G. Schutgens reports grants from Bayer, Baxalta, Pfizer, and Novo Nordisk outside the submitted work. M. Peters reports a grant from Pfizer outside the submitted work. W.L. van Heerde reports financial support from Takeda, Bayer, Sobi and CSL Behring, and funding from Takeda and Bayer for Enzyre. The remaining authors declare no competing financial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Women with rare bleeding disorders (RBDs), including coagulation factor deficiencies and fibrinolytic disorders, may have a higher risk of postpartum hemorrhage (PPH). Information on this patient category is lacking in the existing PPH guidelines because data on PPH in patients with RBDs are scarce., Objective: To describe the prevalence of PPH in women with an RBD and evaluate the use of peripartum hemostatic prophylaxis., Methods: In the Rare Bleeding Disorders in the Netherlands (RBiN) study, patients with RBDs (n = 263) were included from all 6 Dutch hemophilia treatment centers. Patient-reported information on delivery, peripartum hemostatic prophylaxis, and occurrence of PPH was collected retrospectively. If available, information about the precise volume of postpartum blood loss was extracted from electronic patient files. PPH was defined as blood loss ≥500 mL (World Health Organization guideline)., Results: A total of 244 pregnancies, including 193 livebirths, were reported by 85 women. A considerable proportion of these women experienced PPH, ranging from 30% in factor V deficiency to 100% in hyperfibrinolysis. Overall, PPH was reported in 44% of deliveries performed with and 53% of deliveries performed without administration of peripartum hemostatic prophylaxis. Blood loss was significantly higher in deliveries without administration of hemostatic prophylaxis (median 1000 mL) compared to deliveries with administration of prophylaxis (median 400 mL) (p = 0.011). Patients with relatively mild deficiencies also frequently experienced PPH when peripartum hemostatic prophylaxis was omitted., Conclusion: PPH is common in rare coagulation factor deficiencies, both severe and mild, and fibrinolytic disorders, especially when peripartum prophylactic hemostatic treatment was not administered. The use of prophylactic hemostatic treatment was associated with less postpartum blood loss., Competing Interests: Declaration of competing interests K.M. reports speaker fees from Bayer and Alexion, participation in trial steering committee for Bayer, consulting fees from Uniqure, and participation in data monitoring and endpoint adjudication committee for Octapharma. M.H.C. received investigator–initiated research and travel grants, as well as speaker fees, over the years from the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch “Innovatiefonds Zorgverzekeraars,” Baxter, Baxalta, Shire, Takeda, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma and has served as a steering board member for Roche, Bayer, and Novartis. All grants, awards, and fees go to the Erasmus MC as institution. R.E.G.S. reports grants from Bayer, Baxalta, Pfizer, and Novo Nordisk outside the submitted work. M.P. reports a grant from Pfizer outside the submitted work. W.L.v.H. reports financial support from Takeda, Bayer, Sobi, and CSL Behring and funding from Takeda and Bayer for Enzyre. The remaining authors declare no competing financial interests., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Patients with rare inherited bleeding disorders (RBDs) exhibit hemorrhagic symptoms, varying in type and severity, often requiring only on-demand treatment. Prolonged bleeding after invasive procedures is common. Adequate peri-procedural therapy may reduce this bleeding risk., Objective: To describe general treatment plans of RBD patients and evaluate the use of peri-procedural hemostatic therapy., Methods: In the Rare Bleeding Disorders in the Netherlands (RBiN) study, RBD patients from all six Dutch Hemophilia Treatment Centers were included. General treatment plans were extracted from patient files. Patients with a dental or surgical procedure in their history were interviewed about use of peri-procedural treatment and bleeding complications., Results: Two-hundred sixty-three patients with a rare coagulation factor deficiency or fibrinolytic disorder were included. Eighty-four percent had a documented general treatment plan. General treatment plans of patients with the same RBD were heterogeneous, particularly in factor XI deficiency. Overall, 308 dental and 408 surgical procedures were reported. Bleeding occurred in 50% of dental and 53% of surgical procedures performed without hemostatic treatment and in 28% of dental and 19% of surgical procedures performed with hemostatic treatment. Not only patients with severe RBDs, but also patients with mild deficiencies, experienced increased bleeding without proper hemostatic treatment., Conclusion: Large heterogeneity in general treatment plans of RBD patients was found. Bleeding after invasive procedures was reported frequently, both before and after RBD diagnosis, irrespective of factor activity levels and particularly when peri-procedural treatment was omitted. Improved guidelines should include uniform recommendations for most appropriate hemostatic products per RBD and emphasize the relevance of individual bleeding history., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: An appropriate clinical diagnosis of von Willebrand disease (VWD) can be challenging because of a variable bleeding pattern and laboratory phenotype. Genotyping is a powerful diagnostic tool and may have an essential role in the diagnostic field of VWD., Objectives: To unravel the clinical and laboratory heterogeneity of genetically confirmed VWD type 2M patients and to investigate their relationship., Methods: Patients with a confirmed VWD type 2M genetic variant in the A1 or A3 domain of von Willebrand factor (VWF) and normal or only slightly aberrant VWF multimers were selected from all subjects genotyped at the Radboud university medical center because of a high suspicion of VWD. Bleeding scores and laboratory results were analyzed., Results: Fifty patients had a clinically relevant genetic variant in the A1 domain. Median bleeding score was 5. Compared with the nationwide Willebrand in the Netherlands study type 2 cohort, bleeding after surgery or delivery was reported more frequently and mucocutaneous bleedings less frequently. Median VWF activity/VWF antigen (VWF:Act/VWF:Ag) ratio was 0.32, whereas VWF collagen binding activity/VWF antigen (VWF:CB/VWF:Ag) ratio was 0.80. Variants in the A3 domain were only found in two patients with low to normal VWF:Act/VWF:Ag ratios (0.45, 1.03) and low VWF:CB/VWF:Ag ratios (0.45, 0.63)., Conclusion: Genetically confirmed VWD type 2M patients have a relatively mild clinical phenotype, except for bleeding after surgery and delivery. Laboratory phenotype is variable and depends on the underlying genetic variant. Addition of genotyping to the current phenotypic characterization may improve diagnosis and classification of VWD., (© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)