Should von Willebrand disease be considered in a patient with a complex medical history and symptoms suggestive of a bleeding disorder, taking Relafen (nabumetone)?

Von Willebrand Disease Should Be Strongly Considered

Yes, von Willebrand disease (VWD) is absolutely a potential consideration in this patient, particularly given the bleeding symptoms and NSAID use (nabumetone), which can exacerbate bleeding risk in patients with underlying hemostatic disorders. 1

Why VWD Must Be Considered

Clinical Context Supporting VWD Evaluation

• NSAIDs like nabumetone inhibit platelet aggregation and prolong bleeding time, creating a "double hit" scenario where an underlying bleeding disorder becomes clinically apparent 2
• The drug label specifically warns that "patients receiving nabumetone who may be adversely affected by alterations in platelet function, such as those with coagulation disorders, should be carefully monitored" 2
• VWD is the most common inherited bleeding disorder, making it statistically the first consideration when bleeding symptoms emerge 3

Key Clinical Scenarios Requiring VWD Assessment

The NHLBI/NIH guidelines identify two critical scenarios where VWD evaluation is warranted 1:

1. Persons presenting with personal and/or family history of bleeding symptoms - this appears applicable to your patient
2. Asymptomatic persons undergoing surgical/invasive procedures who need bleeding risk assessment

Diagnostic Approach

Initial Clinical Screening

Ask these three preoperative screening questions (Grade B-C recommendations) 1:

• Has the patient experienced excessive bleeding from minor wounds or surgical procedures?
• Does the patient have a family history of bleeding problems?
• Has the patient experienced easy bruising, frequent nosebleeds, or prolonged bleeding from minor cuts?

If any answer is positive, proceed to the nine additional detailed bleeding questions and physical examination 1

Physical Examination Findings to Assess

Look specifically for 1:

• Ecchymoses, hematomas, petechiae - evidence of recent bleeding
• Signs of anemia - from chronic blood loss
• Mucocutaneous bleeding patterns - epistaxis, oral cavity bleeding, easy bruising 4
• Alternative diagnoses: jaundice (liver disease), splenomegaly, joint/skin laxity (Ehlers-Danlos), telangiectasia (hereditary hemorrhagic telangiectasia)

Laboratory Testing Algorithm

Initial hemostasis screening tests (Grade C recommendations) 1, 5:

• Complete blood count (CBC) with platelets and peripheral smear
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT)

Critical caveat: The American Society of Hematology warns that PT and aPTT alone will miss VWD and mild platelet function disorders 5. These tests do not evaluate for VWD but can identify coagulation factor deficiency or thrombocytopenia 1

If mucocutaneous bleeding history is strong, order initial VWD assays immediately (Grade B recommendations) 1, 5:

• VWF antigen (VWF:Ag)
• VWF ristocetin cofactor activity (VWF:RCo)
• Factor VIII coagulant activity (FVIII)

All three tests are required for initial evaluation and can establish diagnosis, type, and severity 1, 5

Interpretation Triggers for Further Testing

Proceed to specialized VWD assays if 1, 5:

• One or more test results are abnormally low
• Ratio of VWF:RCo to VWF:Ag is below 0.5-0.7

VWF multimer analysis should only be performed after abnormal initial results, not for screening 1, 5

Special Considerations in This Case

Acquired von Willebrand Syndrome (AVWS)

Consider AVWS if the patient has abnormal VWF results and bleeding symptoms WITHOUT a personal/family history consistent with hereditary VWD 1. AVWS can be associated with various medical conditions and presents with laboratory findings similar to congenital VWD 1

Low VWF (30-50 IU/dL) Diagnostic Challenge

• Patients with VWF levels between 30-50 IU/dL represent a diagnostic gray zone 6
• Heavy menstrual bleeding and postpartum hemorrhage can cause significant morbidity even with mild VWF reductions 6
• Bleeding phenotype correlates poorly with residual VWF levels in this range 6
• Most low VWF patients lack detectable pathogenic VWF variants, suggesting complex pathobiology 6

NSAID Effect Amplification

The combination of nabumetone's antiplatelet effects with potential underlying VWD creates heightened bleeding risk 2. The reversible platelet dysfunction from NSAIDs may unmask previously subclinical VWD 2

Common Pitfalls to Avoid

• Do not rely solely on PT/aPTT to exclude bleeding disorders - this misses VWD entirely 5
• Do not overlook VWD testing in patients with normal PT/aPTT but mucocutaneous bleeding 5
• Do not fail to obtain a structured bleeding history using validated assessment tools 5
• Do not order VWF multimer analysis as initial screening - it is technically complex and should only follow abnormal initial VWD testing 1, 5

Bottom Line

An increasing number of positive responses to bleeding questions and abnormal physical examination findings increase the likelihood of VWD 1. Given the patient's complex history, bleeding symptoms, and NSAID exposure, VWD evaluation with the three initial VWF tests (VWF:Ag, VWF:RCo, FVIII) is warranted and should be pursued promptly 1, 5.