Hemorrhagic DisordersBDUC-iNNCT07454161
Bleeding Disorder of Unknown Cause in the Netherlands
An observational study of Hemorrhagic Disorders and Bleeding Disorder of Unknown Cause, run by Maastricht University Medical Center at 8 sites in Netherlands.
Trial summary
The purpose of the Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) is to learn more about unexplained bleeding in individuals with a bleeding disorder of unknown cause (BDUC). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Hemorrhagic Disorders, Bleeding Disorder of Unknown Cause
- How many people
- 500 participants
- Where
- 8 sitesNetherlands
- Study dates
- 1 Jun 2026to 1 Mar 2039
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals aged ≥12 years with a clinically relevant increased bleeding tendency, based on an elevated ISTH Bleeding Assessment Tool (ISTH-BAT) score or the clinical view of a (pediatric) hemostasis specialist, who remain undiagnosed following comprehensive laboratory investigation and are consequently classified as having a bleeding disorder of unknown cause (BDUC), will be identified at one of the six Hemophilia treatment centers in the Netherlands and approached for study participation by their treating physician.
Who may be able to join
- Referred to a (pediatric) hemostasis specialist for evaluation of bleeding tendency.
- Increased bleeding tendency based on: Abnormal International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) score (≥ 5 in women age 18-30; ≥ 6 in women age 31-51, ≥ 7 in women age 52 or older; ≥4 in men and ≥ 3 in children) OR Clinical gestalt according to the investigating physician
- Absence of diagnostic test results for a bleeding disorder in standard laboratory hemostasis tests:
- Complete blood count: Hemoglobin > 6.0 mmol/L; thrombocyte count > 100 x10^9/L
- Prothrombin (PT) and activated Partial Thromboplastin Time (aPTT): within local reference range, or prolonged without explanatory factor deficiency
- Fibrinogen activity, von Willebrand Factor (VWF) antigen \& activity, Factor VIII, IX, XI and XIII: within local reference range or abnormal but not explaining bleeding phenotype
Show all 9Show fewer
- Light transmission aggregometry (LTA): Not diagnostic for a platelet function
- Kidney function: eGFR > 45 ml/min
- Liver function: ALAT, bilirubin < 3 x upper limit of normal
Who cannot join
- Use of medication interfering with laboratory hemostasis tests which cannot be stopped before blood withdrawal
- Pregnancy or lactation at moment of inclusion
- Presence of an established bleeding disorder
- Presence of an acquired cause or another explanation for the increased bleeding tendency
- Inability to provide informed consent
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Netherlands8 sites, 8 recruiting
- Not yet recruiting
Amsterdam University Medical Center
Amsterdam, North Holland, 1105 AZ
- Not yet recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 971 GZ
- Not yet recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
- Recruiting
Maastricht University Medical Center
Maastricht, Limburg, 6228 HX
F.C.J.I. Heubel-Moenen, Dr., +31 (0)43 3876543, floor.moenen@mumc.nl
- Not yet recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6525 GA
- Not yet recruiting
Erasmus Medisch Centrum
Rotterdam, South Holland, 3015 GD
- Not yet recruiting
University Medical Center Utrecht
Utrecht, Utrecht, 3584 CX
- Not yet recruiting
Maxima Medical Center
Veldhoven, North Brabant, 5504 DB
About this study
Official title: Bleeding Disorder of Unknown Cause In the Netherlands (BDUC-iN Study)
The purpose of the Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) is to learn more about unexplained bleeding in individuals with a bleeding disorder of unknown cause (BDUC). The study aims to better understand why these individuals have increased bleeding and how it affects their health and daily life.
The main questions of this study are:
Read more
- What are the mechanisms underlying the bleeding tendency in BDUC?
- How do bleeding symptoms affect patients' daily functioning and overall health-related quality of life?
- How is care delivered to individuals with BDUC, and how can this be improved?
Participants with increased bleeding tendency who remain undiagnosed after standard coagulation testing and are consequently classified as having BDUC will be enrolled across the Hemophilia treatment centers in the Netherlands. Participants will undergo blood sampling for advanced hemostasis testing and genetic analysis. In addition, participants will complete validated questionnaires to assess bleeding symptoms and health-related quality of life. Participants will be followed longitudinally to evaluate how bleeding symptoms affect daily activities, medical procedures, and overall health-related quality of life.
Read the detailed description
Background: Despite advances in laboratory diagnostics, current standard hemostasis tests only identify a hemostatic defect in about 25-50% of individuals who are referred to a hemostasis specialist for evaluation of bleeding symptoms. Individuals presenting with an increased bleeding tendency and in whom no abnormalities can be found with standard laboratory hemostasis tests, and who have no other identifiable cause for their bleeding phenotype, are classified as having a bleeding disorder of unknown cause (BDUC). Persons with BDUC suffer from similar bleeding symptoms and clinical manifestations as those observed in persons with a diagnosed bleeding disorders such as von Willebrand Disease (VWD) or platelet function disorders (PFDs). In daily life, frequently experienced bleeding symptoms in patients with BDUC such as heavy menstrual bleeding or epistaxis are known to have a major impact on social functioning, school or work-related activities, and consequently result in reduced health-related quality of life. Due to a lack of knowledge about the underlying pathophysiological cause of the bleeding tendency, there is currently no clear guideline or consensus available for treating persons with BDUC. The lack of a clear diagnosis of BDUC is therefore challenging for both the individual and the treating physician.
Objectives: The Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) aims to improve diagnostic accuracy and optimize treatment strategies in persons with BDUC, by evaluating the pathophysiological mechanisms underlying the bleeding tendency. Additionally, the BDUC-iN study aims to identify and evaluate healthcare delivery, patient outcomes and health-related quality of life among persons with BDUC.
Methods: This study is a multicenter, observational cohort study involving 500 individuals with BDUC registered at or investigated in one of the six Hemophilia Treatment Centers in the Netherlands. Diagnostic, therapeutic and fundamental research questions are organized into eleven dedicated work packages. Clinical data is collected over a 10-year follow-up period to evaluate changes over time. The impact of bleeding symptoms on health-related quality of life is assessed using validated questionnaires. Advanced hemostasis and fibrinolytic testing, platelet function assessments and proteogenomics analysis are performed to characterise bleeding phenotypes and identify hemostasis defects. In addition, targeted therapeutic interventions are tested in vitro to assess their impact on platelet adhesion, thrombus formation and thrombin generation. A care pathway framework is developed, which will incorporate findings from the collected clinical, laboratory and patient-reported data, as well as additional focus groups with patients and treating physicians, with the aim of identifying areas for improvement in diagnosis and treatment management.
- Keywords
- Bleeding disorder of unknown cause, Hemostasis, Diagnosis, Management, Pathofysiology, Quality of life, Prospective
- Medical subject headings
- Hemorrhagic Disorders, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Bleeding Disorder of Unknown Cause | This cohort consists of patients aged ≥12 years presenting with a clinically relevant increased bleeding tendency, as determined by a medical specialist or indicated by an elevated ISTH Bleeding Assessment Tool (ISTH-BAT) score, who remain without a definitive hemostatic diagnosis after extensive laboratory evaluation. These individuals are classified as having a bleeding disorder of unknown cause (BDUC). The bleeding phenotype in this cohort is generally similar to that of patients with established coagulation disorders. Participants frequently experience an increased risk of bleeding during daily life (e.g., heavy menstrual bleeding) and during medical procedures such as surgery, dental interventions, or childbirth, as well as following trauma. In this study, participants will undergo blood sampling for advanced hemostasis and genetic analysis, complete questionnaires, and be followed longitudinally to assess the impact of bleeding on health-related quality of life. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health-related quality of life
Using the Patient-Reported Outcomes Measurement Information System (PROMIS) in adults and the Pediatric Quality of Life Inventory (PedsQL) in children. PROMIS: responses are converted into T-scores, where higher scores indicate a greater level of the concept being measured (e.g., higher physical function or greater pain, depending on the domain). PedsQL: range 0-100 scale, with higher scores indicating better HRQoL.
Measured: From enrollment to the end at 10 years
Diagnostic yield
The diagnostic yield of advanced platelet function, hemostasis and fibrinolytic testing in individuals with BDUC, by examining the frequency and nature of the identified hemostasis abnormalities and their potential relevance to the bleeding phenotype.
Measured: At baseline
Secondary outcomes (19)
Bleeding symptoms
Prevalence of bleeding symptoms in patients with BDUC.
Measured: From enrollment to the end at 10 years
Bleeding severity
Bleeding severity, using the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT). Range 0 to 56, with higher scores indicating a greater number and/or severity of bleeding symptoms.
Measured: From enrollment to the end at 10 years
Physical activity
Physical activity using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH). Responses are converted into a total activity score, with higher scores indicating higher levels of physical activity.
Measured: From enrollment to the end at 10 years
Patient activation
Patient activation measured using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH). Responses are converted into a total activity score, with higher scores indicating higher levels of physical activity.
Measured: From enrollment to the end at 10 years
Diagnostic delay
The time (in years) between the onset of bleeding symptoms and the establishment of a BDUC diagnosis.
Measured: At baseline
Outcomes of hemostatic challenges
Occurrence of bleeding complications after surgery and childbirth.
Measured: From enrollment to the end at 10 years
Care pathways
Visualisation of the care pathway in BDUC including diagnostic procedures and follow up strategies.
Measured: From enrollment to the end at 10 years
Patient satisfaction with care
Patient satisfaction with current care will be assessed using semi-structured interviews and focus groups, and analyzed using thematic analysis to generate overarching themes reflecting patient satisfaction, reported as qualitative themes.
Measured: From enrollment to the end at 10 years
Platelet function disorder
Number of patients with a (flow-dependent) platelet function disorder.
Measured: At baseline
Rare factor deficiency
Number of patients with a rare factor deficiency.
Measured: At baseline
Fibrinolytic disorders
Number of patients with a fibrinolytic disorder.
Measured: At baseline
Anticoagulant abundance
Number of patients with an anticoagulant abundance.
Measured: At baseline
Endothelial dysfunction
Number of patients with signs of endothelial dysfunction, using ex vivo patient-derived cellular models.
Measured: From enrollment to the end at 10 years
Genetic and proteomic variants
Identification of proteoforms and genetic variants associated with BDUC, including the detection of novel proteoforms and haemostatic modifiers that may contribute to the bleeding phenotype.
Measured: At baseline
Stratification of BDUC subgroups
Subgroups classification of persons with BDUC based on abnormalities in platelet, hemoglobin, and leukocyte parameters using rich full blood count data, in combination with clinical and laboratory characteristics.
Measured: From enrollment to the end at 10 years
Tranexamic acid supplementation
In vitro difference in thrombus formation before and after supplementation of tranexamic acid.
Measured: From enrollment to the end at 10 years
Platelet supplementation
In vitro difference in thrombus formation before and after supplementation of platelets.
Measured: From enrollment to the end at 10 years
von Willebrand factor/factor VIII supplementation
In vitro difference in thrombus formation before and after supplementation of von Willebrand factor/factor VIII.
Measured: From enrollment to the end at 10 years
AI driven prediction model for bleeding
Development of AI driven prediction model for bleeding in patients with BDUC, leveraging patient clinical profiles and biomarker data.
Measured: From enrollment to the end at 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start1 Jun 2026
- Primary completion1 Mar 2039 (estimated)
- Study completion1 Mar 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Hemorrhagic DisordersStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sanquin Research & Blood Bank Divisions
- Responsible party
- Sponsor
- Investigators
- F.C.J.I. Heubel-Moenen, Dr., Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07454161
- Sponsor's protocol ID
- NL87370.068.24
- Acronym
- BDUC-iN
- Status last verified
- Oct 2026
- First submitted
- 2 Mar 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Monard ALL, Mussert CMA, van Duijl TT, Kruip MJHA, Henskens YMC, van den Biggelaar M, Schutgens REG, Schols SEM, Fijnvandraat KJ, Meijer K, den Exter PL, Nieuwenhuizen L, van Moort I, Baker RI, O'Donnell JS, Cnossen MH, Heubel-Moenen FCJI. Bleeding disorder of unknown cause: an illustrated review on current practice, knowledge gaps, and future perspectives. Res Pract Thromb Haemost. 2024 Nov 13;8(8):102625. doi: 10.1016/j.rpth.2024.102625. eCollection 2024 Nov.
PubMed 39687924Mussert CMA, Monard ALL, van Duijl TT, Henskens YMC, van den Biggelaar M, Schutgens REG, Schols SEM, Fijnvandraat KJ, Meijer K, den Exter PL, Nieuwenhuizen L, van Moort I, Kruip MJHA, Cnossen MH, Heubel-Moenen FCJI; BDUC-iN study group. Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey. Haemophilia. 2025 Jul;31(4):752-760. doi: 10.1111/hae.70065. Epub 2025 May 27.
PubMed 40421900Monard ALL, Hellenbrand D, Verhezen P, Beckers EAM, Henskens YCM, Heubel-Moenen FCJI. tPA-ROTEM identifies hyperfibrinolytic profile in a significant proportion of patients with bleeding disorder of unknown cause (BDUC). Thromb Res. 2025 Sep;253:109404. doi: 10.1016/j.thromres.2025.109404. Epub 2025 Jul 16.
PubMed 40680469Mehic D, Schwarz S, Shulym I, Ay C, Pabinger I, Gebhart J. Health-related quality of life is impaired in bleeding disorders of unknown cause: results from the Vienna Bleeding Biobank. Res Pract Thromb Haemost. 2023 Aug 22;7(6):102176. doi: 10.1016/j.rpth.2023.102176. eCollection 2023 Aug.
PubMed 37720482van Duijl TT, Gouw S, Kronevska I, Kooiker A, Kopatz WF, Freato N, Beijlevelt M, Hamer HM, Fijnvandraat K, Meijers JCM, van den Biggelaar M. F9 missense variant hot spots associated with qualitative protein defects causing hemophilia B. Blood Vessel Thromb Hemost. 2025 Jul 18;2(4):100095. doi: 10.1016/j.bvth.2025.100095. eCollection 2025 Nov.
PubMed 41356341Heubel-Moenen FCJI, Brouns SLN, Herfs L, Boerenkamp LS, Jooss NJ, Wetzels RJH, Verhezen PWM, Machiels P, Megy K, Downes K, Heemskerk JWM, Beckers EAM, Henskens YMC. Multiparameter platelet function analysis of bleeding patients with a prolonged platelet function analyser closure time. Br J Haematol. 2022 Mar;196(6):1388-1400. doi: 10.1111/bjh.18003. Epub 2022 Jan 10.
PubMed 35001370Baker RI, Choi P, Curry N, Gebhart J, Gomez K, Henskens Y, Heubel-Moenen F, James P, Kadir RA, Kouides P, Lavin M, Lordkipanidze M, Lowe G, Mumford A, Mutch N, Nagler M, Othman M, Pabinger I, Sidonio R, Thomas W, O'Donnell JS; ISTH SSC Von Willebrand Factor, Platelet Physiology, and Women's Health Issues in Thrombosis and Haemostasis. Standardization of definition and management for bleeding disorder of unknown cause: communication from the SSC of the ISTH. J Thromb Haemost. 2024 Jul;22(7):2059-2070. doi: 10.1016/j.jtha.2024.03.005. Epub 2024 Mar 20.
PubMed 38518896MacDonald S, Wright A, Beuche F, Downes K, Besser M, Symington E, Kelly A, Thomas W. Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment. Int J Lab Hematol. 2020 Apr;42(2):116-125. doi: 10.1111/ijlh.13124. Epub 2019 Nov 20.
PubMed 31747136Thomas W, Downes K, Desborough MJR. Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management. Haemophilia. 2020 Nov;26(6):946-957. doi: 10.1111/hae.14174. Epub 2020 Oct 23.
PubMed 33094877
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bleeding Disorder of Unknown Cause In the Netherlands (BDUC-iN Study)
- ClinicalTrials.gov ID
- NCT07454161
- Acronym / sponsor ID
- BDUC-iN / NL87370.068.24
- Keywords
- Bleeding disorder of unknown cause, Hemostasis, Diagnosis, Management, Pathofysiology, Quality of life, Prospective
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Sanquin Research & Blood Bank Divisions
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 1 Mar 2039 (estimated)
- Study completion
- 1 Mar 2039 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) is to learn more about unexplained bleeding in individuals with a bleeding disorder of unknown cause (BDUC). The study aims to better understand why these individuals have increased bleeding and how it affects their health and daily life.
The main questions of this study are:
- What are the mechanisms underlying the bleeding tendency in BDUC?
- How do bleeding symptoms affect patients' daily functioning and overall health-related quality of life?
- How is care delivered to individuals with BDUC, and how can this be improved?
Participants with increased bleeding tendency who remain undiagnosed after standard coagulation testing and are consequently classified as having BDUC will be enrolled across the Hemophilia treatment centers in the Netherlands. Participants will undergo blood sampling for advanced hemostasis testing and genetic analysis. In addition, participants will complete validated questionnaires to assess bleeding symptoms and health-related quality of life. Participants will be followed longitudinally to evaluate how bleeding symptoms affect daily activities, medical procedures, and overall health-related quality of life.
Detailed description
Background: Despite advances in laboratory diagnostics, current standard hemostasis tests only identify a hemostatic defect in about 25-50% of individuals who are referred to a hemostasis specialist for evaluation of bleeding symptoms. Individuals presenting with an increased bleeding tendency and in whom no abnormalities can be found with standard laboratory hemostasis tests, and who have no other identifiable cause for their bleeding phenotype, are classified as having a bleeding disorder of unknown cause (BDUC). Persons with BDUC suffer from similar bleeding symptoms and clinical manifestations as those observed in persons with a diagnosed bleeding disorders such as von Willebrand Disease (VWD) or platelet function disorders (PFDs). In daily life, frequently experienced bleeding symptoms in patients with BDUC such as heavy menstrual bleeding or epistaxis are known to have a major impact on social functioning, school or work-related activities, and consequently result in reduced health-related quality of life. Due to a lack of knowledge about the underlying pathophysiological cause of the bleeding tendency, there is currently no clear guideline or consensus available for treating persons with BDUC. The lack of a clear diagnosis of BDUC is therefore challenging for both the individual and the treating physician.
Objectives: The Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) aims to improve diagnostic accuracy and optimize treatment strategies in persons with BDUC, by evaluating the pathophysiological mechanisms underlying the bleeding tendency. Additionally, the BDUC-iN study aims to identify and evaluate healthcare delivery, patient outcomes and health-related quality of life among persons with BDUC.
Methods: This study is a multicenter, observational cohort study involving 500 individuals with BDUC registered at or investigated in one of the six Hemophilia Treatment Centers in the Netherlands. Diagnostic, therapeutic and fundamental research questions are organized into eleven dedicated work packages. Clinical data is collected over a 10-year follow-up period to evaluate changes over time. The impact of bleeding symptoms on health-related quality of life is assessed using validated questionnaires. Advanced hemostasis and fibrinolytic testing, platelet function assessments and proteogenomics analysis are performed to characterise bleeding phenotypes and identify hemostasis defects. In addition, targeted therapeutic interventions are tested in vitro to assess their impact on platelet adhesion, thrombus formation and thrombin generation. A care pathway framework is developed, which will incorporate findings from the collected clinical, laboratory and patient-reported data, as well as additional focus groups with patients and treating physicians, with the aim of identifying areas for improvement in diagnosis and treatment management.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bleeding Disorder of Unknown Cause | – | –This cohort consists of patients aged ≥12 years presenting with a clinically relevant increased bleeding tendency, as determined by a medical specialist or indicated by an elevated ISTH Bleeding Assessment Tool (ISTH-BAT) score, who remain without a definitive hemostatic diagnosis after extensive laboratory evaluation. These individuals are classified as having a bleeding disorder of unknown cause (BDUC). The bleeding phenotype in this cohort is generally similar to that of patients with established coagulation disorders. Participants frequently experience an increased risk of bleeding during daily life (e.g., heavy menstrual bleeding) and during medical procedures such as surgery, dental interventions, or childbirth, as well as following trauma. In this study, participants will undergo blood sampling for advanced hemostasis and genetic analysis, complete questionnaires, and be followed longitudinally to assess the impact of bleeding on health-related quality of life. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals aged ≥12 years with a clinically relevant increased bleeding tendency, based on an elevated ISTH Bleeding Assessment Tool (ISTH-BAT) score or the clinical view of a (pediatric) hemostasis specialist, who remain undiagnosed following comprehensive laboratory investigation and are consequently classified as having a bleeding disorder of unknown cause (BDUC), will be identified at one of the six Hemophilia treatment centers in the Netherlands and approached for study participation by their treating physician.
Key inclusion criteria (9 listed)
- Referred to a (pediatric) hemostasis specialist for evaluation of bleeding tendency.
- Increased bleeding tendency based on: Abnormal International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) score (≥ 5 in women age 18-30; ≥ 6 in women age 31-51, ≥ 7 in women age 52 or older; ≥4 in men and ≥ 3 in children) OR Clinical gestalt according to the investigating physician
- Absence of diagnostic test results for a bleeding disorder in standard laboratory hemostasis tests:
- Complete blood count: Hemoglobin > 6.0 mmol/L; thrombocyte count > 100 x10^9/L
- Prothrombin (PT) and activated Partial Thromboplastin Time (aPTT): within local reference range, or prolonged without explanatory factor deficiency
Key exclusion criteria (5 listed)
- Use of medication interfering with laboratory hemostasis tests which cannot be stopped before blood withdrawal
- Pregnancy or lactation at moment of inclusion
- Presence of an established bleeding disorder
- Presence of an acquired cause or another explanation for the increased bleeding tendency
- Inability to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Health-related quality of life
Time frame: From enrollment to the end at 10 years
Using the Patient-Reported Outcomes Measurement Information System (PROMIS) in adults and the Pediatric Quality of Life Inventory (PedsQL) in children. PROMIS: responses are converted into T-scores, where higher scores indicate a greater level of the concept being measured (e.g., higher physical function or greater pain, depending on the domain). PedsQL: range 0-100 scale, with higher scores indicating better HRQoL.
Diagnostic yield
Time frame: At baseline
The diagnostic yield of advanced platelet function, hemostasis and fibrinolytic testing in individuals with BDUC, by examining the frequency and nature of the identified hemostasis abnormalities and their potential relevance to the bleeding phenotype.
19 secondary outcomes
Bleeding symptoms
Time frame: From enrollment to the end at 10 years
Bleeding severity
Time frame: From enrollment to the end at 10 years
Physical activity
Time frame: From enrollment to the end at 10 years
Patient activation
Time frame: From enrollment to the end at 10 years
Diagnostic delay
Time frame: At baseline
Outcomes of hemostatic challenges
Time frame: From enrollment to the end at 10 years
Care pathways
Time frame: From enrollment to the end at 10 years
Patient satisfaction with care
Time frame: From enrollment to the end at 10 years
Platelet function disorder
Time frame: At baseline
Rare factor deficiency
Time frame: At baseline
Fibrinolytic disorders
Time frame: At baseline
Anticoagulant abundance
Time frame: At baseline
Endothelial dysfunction
Time frame: From enrollment to the end at 10 years
Genetic and proteomic variants
Time frame: At baseline
Stratification of BDUC subgroups
Time frame: From enrollment to the end at 10 years
Tranexamic acid supplementation
Time frame: From enrollment to the end at 10 years
Platelet supplementation
Time frame: From enrollment to the end at 10 years
von Willebrand factor/factor VIII supplementation
Time frame: From enrollment to the end at 10 years
AI driven prediction model for bleeding
Time frame: From enrollment to the end at 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Background: PubMed 39687924Monard ALL, Mussert CMA, van Duijl TT, Kruip MJHA, Henskens YMC, van den Biggelaar M, Schutgens REG, Schols SEM, Fijnvandraat KJ, Meijer K, den Exter PL, Nieuwenhuizen L, van Moort I, Baker RI, O'Donnell JS, Cnossen MH, Heubel-Moenen FCJI. Bleeding disorder of unknown cause: an illustrated review on current practice, knowledge gaps, and future perspectives. Res Pract Thromb Haemost. 2024 Nov 13;8(8):102625. doi: 10.1016/j.rpth.2024.102625. eCollection 2024 Nov.
- Background: PubMed 40421900Mussert CMA, Monard ALL, van Duijl TT, Henskens YMC, van den Biggelaar M, Schutgens REG, Schols SEM, Fijnvandraat KJ, Meijer K, den Exter PL, Nieuwenhuizen L, van Moort I, Kruip MJHA, Cnossen MH, Heubel-Moenen FCJI; BDUC-iN study group. Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey. Haemophilia. 2025 Jul;31(4):752-760. doi: 10.1111/hae.70065. Epub 2025 May 27.
- Background: PubMed 40680469Monard ALL, Hellenbrand D, Verhezen P, Beckers EAM, Henskens YCM, Heubel-Moenen FCJI. tPA-ROTEM identifies hyperfibrinolytic profile in a significant proportion of patients with bleeding disorder of unknown cause (BDUC). Thromb Res. 2025 Sep;253:109404. doi: 10.1016/j.thromres.2025.109404. Epub 2025 Jul 16.
- Background: PubMed 37720482Mehic D, Schwarz S, Shulym I, Ay C, Pabinger I, Gebhart J. Health-related quality of life is impaired in bleeding disorders of unknown cause: results from the Vienna Bleeding Biobank. Res Pract Thromb Haemost. 2023 Aug 22;7(6):102176. doi: 10.1016/j.rpth.2023.102176. eCollection 2023 Aug.
- Background: PubMed 41356341van Duijl TT, Gouw S, Kronevska I, Kooiker A, Kopatz WF, Freato N, Beijlevelt M, Hamer HM, Fijnvandraat K, Meijers JCM, van den Biggelaar M. F9 missense variant hot spots associated with qualitative protein defects causing hemophilia B. Blood Vessel Thromb Hemost. 2025 Jul 18;2(4):100095. doi: 10.1016/j.bvth.2025.100095. eCollection 2025 Nov.
- Background: PubMed 35001370Heubel-Moenen FCJI, Brouns SLN, Herfs L, Boerenkamp LS, Jooss NJ, Wetzels RJH, Verhezen PWM, Machiels P, Megy K, Downes K, Heemskerk JWM, Beckers EAM, Henskens YMC. Multiparameter platelet function analysis of bleeding patients with a prolonged platelet function analyser closure time. Br J Haematol. 2022 Mar;196(6):1388-1400. doi: 10.1111/bjh.18003. Epub 2022 Jan 10.
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- Background: PubMed 31747136MacDonald S, Wright A, Beuche F, Downes K, Besser M, Symington E, Kelly A, Thomas W. Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment. Int J Lab Hematol. 2020 Apr;42(2):116-125. doi: 10.1111/ijlh.13124. Epub 2019 Nov 20.
- Background: PubMed 33094877Thomas W, Downes K, Desborough MJR. Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management. Haemophilia. 2020 Nov;26(6):946-957. doi: 10.1111/hae.14174. Epub 2020 Oct 23.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
F.C.J.I. Heubel-Moenen, Dr. principal investigator
Maastricht University Medical Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemorrhagic Disorders and Bleeding Disorder of Unknown Cause, run by Maastricht University Medical Center at 8 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. F.C.J.I. Heubel-Moenen (+31 (0)43 3876543, floor.moenen@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health-related quality of life (time frame: From enrollment to the end at 10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07454161, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026; AzTrials last refreshed its copy on 6 Nov 2026.