Should patients with bleeding disorders of unknown cause be accepted into an adult bleeding disorder clinic?

Management of Patients with Bleeding Disorders of Unknown Cause in Adult Bleeding Disorder Clinics

Yes, patients with bleeding disorders of unknown cause (BDUC) should be accepted into adult bleeding disorder clinics, as they represent up to 60-70% of patients with mild-moderate bleeding phenotypes and require specialized care despite normal hemostatic testing. 1

Definition and Prevalence of BDUC

• BDUC is characterized by a clear bleeding tendency with normal standard laboratory tests of hemostasis, after excluding other acquired and nonhematological causes of bleeding (e.g., connective tissue disorders, scurvy) 1
• Up to 60-70% of patients investigated for mild-moderate bleeding disorders may be categorized as BDUC, with bleeding phenotypes indistinguishable from established disorders like von Willebrand disease (VWD) or platelet function defects 1, 2
• Recognition and diagnosis of BDUC are increasing, with a recent UK survey showing a steep rise in such registrations over the past decade 1
• The majority of patients identified with BDUC are female, likely due to the additional hemostatic challenges of menstruation 1

Diagnostic Approach for BDUC

• Diagnosis relies on physician awareness, clinical experience (clinical gestalt), and objective assessment of bleeding measured by an increased bleeding assessment tool (BAT) score 1, 2
• Most experts (80%) use a bleeding score, most frequently the ISTH BAT score (73%), as a standardized approach for assessing bleeding phenotype 1
• Initial hemostatic testing should include activated partial thromboplastin time, prothrombin time, Clauss fibrinogen, VWF antigen and function assays, and coagulation factor assays for FVIII, FIX, and FXI 1
• Assessment for hypermobility using the Beighton score should be part of the initial evaluation, though currently only 55% of clinicians report doing this 1
• BDUC is a diagnosis of exclusion after ruling out VWD, platelet function defects, coagulation factor deficiencies, and non-hemostatic causes for bleeding 3

Clinical Importance of Managing BDUC in Specialized Clinics

• Patients with BDUC may experience significant bleeding complications with surgery, trauma, childbirth, or menstruation, requiring specialized management to minimize morbidity 4
• BAT scores suggest that patients with BDUC display bleeding phenotypes comparable to those seen in patients with VWD or platelet function disorders 2
• Despite the prevalence of BDUC, diagnosis and management commonly pose significant clinical dilemmas that are best addressed in specialized bleeding disorder clinics 2
• Even with extensive testing, approximately 50% of patients with clinically significant bleeding may remain without a definitive diagnosis and be classified as having BDUC 5

Management Considerations in Bleeding Disorder Clinics

• Tranexamic acid is favored for prophylaxis for minor (71%) and major (59%) surgeries and during pregnancy (58%) 1
• Management of heavy menstrual bleeding despite combined oral contraceptive pill use is challenging, with multiple alternative strategies being employed 1
• Antifibrinolytic agents like tranexamic acid may be beneficial as adjunctive therapy 5
• Establishing a mode of inheritance is important to minimize morbidity in family members 4

Pitfalls and Challenges

• Significant variation exists in the recognition, registration, and management of people with BDUC worldwide 1
• There is a need for consensus pathways to diagnose and treat BDUC to standardize and improve care for patients internationally 1
• Accurate distinction between normal and pathological bleeding remains difficult 4
• The pathogenesis of BDUC remains unknown, though it may be a polygenic bleeding disorder or include a combination of different mild disorders 1
• Preanalytical variables can significantly affect platelet function testing results, including medication use, sample processing, and patient stress level 5

By accepting patients with BDUC into adult bleeding disorder clinics, healthcare providers can offer specialized care, preventive strategies, and appropriate interventions to reduce morbidity and improve quality of life in this significant patient population.