Is acquired von Willebrand disease progressive?

Is Acquired von Willebrand Disease Progressive?

Acquired von Willebrand syndrome (AVWS) is not inherently progressive as a disease entity; rather, its course depends entirely on the underlying condition causing it, and it typically resolves when the underlying disorder is successfully treated. 1, 2

Disease Behavior and Natural History

AVWS differs fundamentally from hereditary von Willebrand disease in that it is a secondary phenomenon rather than a primary genetic disorder. The severity and persistence of AVWS directly correlate with the activity and treatment status of the underlying condition 3, 4.

Key Characteristics of AVWS Course:

• Reversibility is the hallmark feature: Treatment of the underlying condition (chemotherapy, radiotherapy, surgery, or immunosuppressants) can result in complete remission of AVWS 1, 5
• Resolution with underlying disease control: Successful treatment of conditions like hypothyroidism or multiple myeloma has led to normalization of coagulation parameters 3
• Not progressive in the traditional sense: Unlike hereditary VWD, AVWS does not worsen over time independent of its underlying cause 4

Context-Specific Progression Patterns

The behavior of AVWS varies significantly based on the underlying etiology:

In Myeloproliferative Neoplasms (Essential Thrombocythemia/Polycythemia Vera):

• AVWS severity correlates with extreme thrombocytosis and corrects with platelet count normalization 6
• The coagulation abnormality is associated with abnormal adsorption of large von Willebrand proteins to clonal platelets 6
• Monitor for new thrombosis, acquired VWD, and disease-related major bleeding as part of ongoing disease surveillance 6

In Severe Aortic Stenosis:

• The acquired von Willebrand syndrome correlates with the severity of AS and resolves after valve replacement, except when prosthetic valve area is inadequate (<0.8 cm²/m²) 6
• This represents a mechanical cause where progression tracks with the underlying valvular disease severity 6

In ECMO Patients:

• AVWS is common but underrecognized in both pediatric and adult ECMO patients 6
• The disorder persists as long as ECMO support continues, representing an ongoing mechanical stress rather than true disease progression 6

Clinical Implications

Critical pitfall: Do not assume AVWS will worsen over time like hereditary VWD. Instead, focus on:

• Identifying and treating the underlying condition as the primary therapeutic goal 1, 2, 5
• Recognizing that AVWS typically occurs in elderly patients with serious underlying conditions 5, 4
• Understanding that bleeding severity varies considerably among patients and depends on the underlying pathogenic mechanism 4

Monitoring Approach:

• Suspect AVWS in any patient with new-onset bleeding and laboratory findings suggesting VWD, particularly with an AVWS-associated disorder 5
• Test prior to surgery or high-bleeding-risk interventions in individuals with AVWS-associated disorders 5
• Serial monitoring is needed only if the underlying condition remains active or untreated 2

Treatment Considerations

The heterogeneous mechanisms of AVWS mean that more than one therapeutic approach is often required for acute bleeds and procedural prophylaxis, including desmopressin, VWF-containing concentrates, IVIG, or plasmapheresis 1. However, these are temporizing measures—definitive management requires addressing the underlying disorder 2, 5.