Von Willebrand Disease: Diagnosis and Clinical Considerations in Patients with Concurrent Thrombosis

Epidemiology

• Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1 % of the general population with a symptomatic prevalence of approximately 0.1 %. 1

Clinical Presentation

• In women who present with recurrent deep‑vein thrombosis (DVT) together with heavy menstrual bleeding that produces large clots, type 2N VWD should be the primary diagnostic consideration because the combination can arise when VWD coexists with thrombophilia or when anticoagulation for DVT unmasks an underlying bleeding disorder. 1
• The presence of large menstrual clots is characteristic of VWD, reflecting impaired platelet adhesion and defective fibrin formation. 1

Initial Laboratory Evaluation (First‑line Tests)

• Recommended first‑line assays for evaluating suspected VWD include:

Diagnostic Thresholds by VWD Subtype

Type 1 VWD

• Diagnosis can be made when VWF:Ag and/or VWF activity < 0.30 IU/mL irrespective of bleeding symptoms, or when levels are < 0.50 IU/mL in patients with documented abnormal bleeding. 2

Type 2N VWD (critical in this scenario)

• VWF antigen and activity may be normal or only mildly reduced.
• FVIII:C is typically reduced to 0.05–0.40 IU/mL, mimicking hemophilia and potentially escaping routine screening.
• Confirmation requires either a VWF:FVIIIB binding assay or targeted genetic testing. 2

Type 3 VWD

• VWF:Ag and activity < 0.05 IU/mL and FVIII:C < 0.10 IU/mL are diagnostic. 2

Timing of Testing and Common Pitfalls

• Avoid testing during active menstrual bleeding because acute blood loss can falsely elevate VWF levels. 1
• VWF concentrations rise with stress, vigorous exercise, estrogen use, and pregnancy; therefore, samples should be drawn when the patient is in a physiologically stable state. 2
• Repeat testing is often necessary to obtain a definitive diagnosis, especially when initial results are borderline or obtained under suboptimal conditions. 2
• Testing during menstruation, pregnancy, or acute stress may yield false‑negative results; VWF is an acute‑phase reactant that increases during inflammation, further confounding interpretation. [2][1]

Importance of Early Diagnosis

• Among adolescents with heavy menstrual bleeding, ≈ 39 % have an underlying bleeding disorder, compared with ≈ 16 % in adult women; early identification prevents prolonged morbidity and facilitates appropriate management. 1

Specific Considerations for Type 2N VWD

• Because type 2N VWD can present with near‑normal VWF antigen/activity, standard VWF assays may miss the diagnosis.
• Specific VWF:FVIIIB binding assays or genetic testing are required to uncover this subtype. 2

All facts are derived from peer‑reviewed evidence (Blood Advances, 2025) and reflect current expert recommendations.