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. 2025 Jul;31(4):752-760.
doi: 10.1111/hae.70065. Epub 2025 May 27.

Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey

Caroline M A Mussert  1 , Amaury L L Monard  2   3 , Tirsa T van Duijl  4 , Yvonne M C Henskens  3   5 , Maartje van den Biggelaar  4 , Roger E G Schutgens  6 , Saskia E M Schols  7 , Karin J Fijnvandraat  8   9 , Karina Meijer  10 , Paul L den Exter  11 , Laurens Nieuwenhuizen  12 , Iris van Moort  13 , Marieke J H A Kruip  13 , Marjon H Cnossen  1 , Floor C J I Heubel-Moenen  2   3 ; BDUC‐iN study group
Affiliations

Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey

Caroline M A Mussert et al. Haemophilia. 2025 Jul.

Abstract

Introduction: About 40%-70% of persons with a clinically relevant bleeding tendency who are referred to haemostasis experts are classified as having a 'bleeding disorder of unknown cause' (BDUC) as no biological entity can be found after extensive laboratory testing. Currently, guidelines are under development regarding diagnostic assessment and management to minimize variation in clinical practice.

Aim: Investigate current practices regarding BDUC in the Netherlands.

Methods: An online survey on the best BDUC definition, associated bleeding phenotype, clinical and diagnostic approaches, treatment, registration, and follow-up was distributed amongst healthcare providers working in Dutch haemophilia treatment centres (HTCs).

Results: The survey was completed by 39/54 (72%) respondents. Twenty percent did not register BDUC patients in their HTC. Healthcare professionals indicated that follow-up should depend on bleeding phenotype severity and bleeding history, and other potential causes for an increased bleeding tendency should be excluded. Moreover, the use of laboratory tests within the routine diagnostic pathway was demonstrated to be heterogeneous. Regarding treatment, tranexamic acid was most frequently prescribed for minor and major surgical interventions (79% and 86%), dental extractions (93%) and childbirth (93%). Desmopressin was prescribed for major surgical procedures by 79%.

Conclusion: Our survey shows that Dutch current practice varies but is generally in line with recent ISTH SSC recommendations. Additionally, it describes other clinically relevant topics not included in the international survey, such as follow-up and exclusion of other causes for bleeding. This survey therefore adds to international efforts to unify BDUC definition, diagnostic approach, treatment and follow-up, and to attain broadly supported guidelines.

Keywords: bleeding disorder of unknown cause; current practice; diagnostics; haemostasis; management.

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Conflict of interest statement

Tirsa T. van Duijl has received research funding from the Bertus Kem Stipendium (GNGH). Yvonne M. C. Henskens is professor of clinical chemistry, in particular haemostasis. In this position she collaborates with and tests reagents and equipment from IVD companies in the field of haemostasis (Werfen, Siemens, Roche, Nodia, Stago). She is also an advisor of Promicol. Roger E. G. Schutgens has received research funding from Bayer, CSL Behring, Hemab, NovoNordisk, Novartis, Octapharma, Sanofi and Sobi. All payments go to the institution. Karin J. Fijnvandraat has received unrestricted grants/research funding from CSL Behring, Sobi for research unrelated to the current study, consultancy fees from Sobi, Sanofi, Novo Nordisk and Roche (all fees to the institution). Other boards: ISTH Standardization Subcommittee on Factor VIII, Factor XI, and Rare Coagulation Disorders. Karina Meijer reports speaker fees from Alexion, participation in trial steering committees for Bayer and Astra Zeneca, consulting fees from Therini, participation in data monitoring and endpoint adjudication committee for Octapharma. All payments go to her institution. Marieke J. H. A. Kruip has received an investigator‐initiated research grant from Dutch Research Council (NWO), The Netherlands Organisation for Health Research and Development (ZonMw), Netherlands thrombosis foundation and Sobi, and speaker fees from Roche and Sobi. All payments go to the Erasmus MC as an institution.

Marjon H. Cnossen has received investigator‐initiated research and travel grants from the Dutch Research Council (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch Healthcare Insurers Innovation Fund, Pfizer, Baxter/Baxalta/Shire/Takeda, Bayer Schering Pharma, CSL Behring, Sobi, Novo Nordisk, Novartis, Nordic Pharma, Roche and Octapharma and has served as a board member for Roche and Bayer. All scholarships, prizes and reimbursements go to Erasmus MC as an institution. Floor C. J. I. Heubel‐Moenen has received an unrestricted research grant from Octapharma and a research fellowship from University of Maastricht. All payments go to the institution. All other authors have no conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Use of diagnostic laboratory tests in persons with an increased bleeding tendency. Respondents were asked which laboratory tests they perform and in which order (first round, second round or third round of laboratory tests, on indication or never) for the diagnosis in persons with an increased bleeding tendency. Answers from the different rounds were combined to indicate the overall use of a specific test. Respondents were able to select multiple answers, for example, that a test is performed within a certain round as well as on indication. Therefore, for some tests the sum exceeds 100%. For each test, the percentage of the most common answer, given by respondents, is shown above the bar. * Laboratory tests in the proposed standard panel in ISTH SSC recommendations.
FIGURE 2
FIGURE 2
Exclusion of bleeding disorders and other causes for an increased bleeding tendency. Fibrin/fibrinogen/fibrinolysis disorders comprise both quantitative and qualitative fibrinogen defects including hyperfibrinogenemia and (hypo)dysfibrinogenemia, as well as fibrinolytic protein deficiencies and/or abnormalities in global fibrinolysis tests (e.g., euglobulin clot lysis time).
FIGURE 3
FIGURE 3
Follow‐up prerequisites and frequency in persons with BDUC. Percentages of neutral answers to statements are not shown. Regarding follow‐up in case of a mild, moderate or severe bleeding phenotype, the selection of multiple answers was possible.
FIGURE 4
FIGURE 4
Treatment strategies in persons with BDUC. A selection of multiple answers was possible for (prophylactic) treatment strategies in case of the various medical procedures.
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