What is the management approach for patients with atypical symptoms of mild to moderate von Willebrand disease (VWD)?

Management of Atypical Presentations of Mild to Moderate Von Willebrand Disease

Patients with atypical symptoms of mild to moderate von Willebrand disease (VWD) should be managed based on their specific VWD subtype, bleeding risk, and clinical presentation, with treatment tailored to correct both VWF deficiency and associated factor VIII abnormalities.

Clinical Presentation of Atypical VWD

• Acquired von Willebrand syndrome (AVWS) may present with atypical symptoms and should be considered in patients with abnormal VWF test results and bleeding symptoms without a personal/family history consistent with hereditary VWD 1
• In aortic stenosis, impaired platelet function and decreased levels of von Willebrand factor can be demonstrated, with severity correlating with the degree of stenosis 1
• Acquired VWD in aortic stenosis is associated with clinical bleeding (epistaxis or ecchymoses) in approximately 20% of patients 1
• Atypical presentations may include bleeding with normal factor VIII levels but abnormal VWF activity 2

Diagnostic Approach for Atypical Presentations

• Initial evaluation should include assessment of personal and family bleeding history, with specific attention to mucocutaneous bleeding patterns 1
• Laboratory testing should include complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and factor VIII activity 1
• The ratio of VWF:RCo/VWF:Ag is crucial for proper classification of VWD type, especially in atypical presentations 2
• Patient factors that can mask underlying VWD by elevating VWF and FVIII levels include stress, recent exercise, inflammatory illness, pregnancy, and oral contraceptives 2
• Sample collection and processing conditions significantly affect test results - ensure proper handling at room temperature and prompt processing 2

Management Strategy Based on VWD Type

Type 1 VWD (Partial Quantitative Deficiency)

• Desmopressin is the treatment of choice for patients with Type 1 VWD with factor VIII and VWF levels ≥10 U/dL 3, 4
• Response to desmopressin should be documented with pre- and post-treatment VWF and FVIII levels 2
• Desmopressin will often maintain hemostasis during surgical procedures when administered 30 minutes prior to the scheduled procedure 3

Type 2 VWD (Qualitative Deficiency)

• Most Type 2 patients do not respond adequately to desmopressin and require VWF/factor VIII concentrates 4, 5
• Type 2B patients should avoid desmopressin as it may induce thrombocytopenia 6

Type 3 VWD (Severe Quantitative Deficiency)

• Desmopressin is ineffective; VWF/factor VIII concentrates are required 7, 4

Acquired VWD

• Treatment should target the underlying condition (e.g., aortic stenosis) 1
• In myeloproliferative disorders with acquired VWD, aspirin should be used with caution due to increased bleeding risk 1

Procedural Management

• For surgical procedures, target VWF activity level should be ≥50 IU/dL 2
• VWF activity should be maintained >50 IU/dL while epidural catheter remains in place for neuraxial procedures 2
• Monitor VWF:RCo, VWF:Ag, and FVIII levels pre-treatment, post-treatment, and periodically during treatment for surgical patients 2

Special Considerations

• In aortic stenosis-associated VWD, valve replacement may resolve the coagulation abnormality except when the prosthetic valve area is small for patient size (less than 0.8 cm² per m²) 1
• For persistent mucosal bleeding despite adequate FVIII levels, consider adjunctive treatments like tranexamic acid 2
• In myeloproliferative neoplasms, cytoreductive therapy (hydroxyurea or anagrelide) with aspirin is recommended for high-risk disease, but aspirin should be used cautiously in patients with acquired VWD 1

Common Pitfalls to Avoid

• Relying solely on FVIII levels for treatment decisions - VWF activity is the critical parameter 2
• Failure to repeat testing under optimal conditions - stress, inflammation, and sample handling can significantly affect results 2
• Overlooking acquired VWD in patients with conditions like aortic stenosis, myeloproliferative disorders, or other medical conditions 1
• Not recognizing that elevated FVIII with normal VWF activity (>50 IU/dL) generally does not require additional treatment for hemostasis 2