What is acquired von Willebrand syndrome?

What is Acquired von Willebrand Syndrome?

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that develops in previously healthy individuals without a family history of bleeding, characterized by deficiency or dysfunction of von Willebrand factor (VWF) secondary to underlying medical conditions rather than genetic inheritance. 1

Key Distinguishing Features from Hereditary VWD

AVWS differs fundamentally from congenital von Willebrand disease in several critical ways:

• No personal or family history of bleeding disorders - patients present with new-onset bleeding symptoms later in life 1
• Associated with underlying medical conditions - the VWF abnormality is secondary to another disease process 2, 3
• Laboratory findings mimic hereditary VWD - making differentiation challenging without careful clinical history 1

Pathophysiologic Mechanisms

AVWS develops through multiple distinct mechanisms depending on the underlying condition 2, 3:

• Antibody-mediated clearance or functional interference - autoantibodies bind to VWF, leading to accelerated clearance or functional inhibition 4, 2
• Adsorption to cell surfaces - VWF binds to transformed cells in lymphoproliferative disorders or to activated platelets in myeloproliferative conditions 2, 3
• Increased shear stress and proteolysis - high shear forces in cardiovascular conditions (aortic stenosis, left ventricular assist devices, ECMO) cause VWF unfolding and cleavage by ADAMTS-13 5, 6
• Decreased synthesis - rarely, the underlying condition reduces VWF production 3

Associated Medical Conditions

The NHLBI guidelines emphasize that AVWS should be considered when specific causative conditions are present 1:

• Lymphoproliferative disorders - most commonly associated, including monoclonal gammopathies and multiple myeloma 4, 2
• Myeloproliferative disorders - essential thrombocythemia and polycythemia vera 2, 3
• Cardiovascular conditions - aortic stenosis, ventricular assist devices, ECMO, congenital heart disease 5, 6
• Autoimmune disorders - systemic lupus erythematosus and other autoimmune conditions 4, 2
• Hypothyroidism - can cause AVWS that resolves with thyroid replacement 4
• Malignancies - various solid tumors 2, 3

Clinical Presentation

Bleeding manifestations in AVWS mirror those of hereditary VWD 1, 4:

• Mucocutaneous bleeding - easy bruising, epistaxis, gingival bleeding 1
• Gastrointestinal bleeding - particularly in cardiovascular-associated AVWS 1
• Menorrhagia - in women of reproductive age 1
• Surgical or procedural bleeding - often the presenting manifestation 1, 5
• Severity ranges from mild to life-threatening - depending on the degree of VWF deficiency 4

Diagnostic Approach

The diagnosis requires high clinical suspicion when bleeding occurs in patients with AVWS-associated conditions but no family history of bleeding disorders. 1, 3

Critical diagnostic elements include:

• Absence of personal and family bleeding history - distinguishes from hereditary VWD 1
• Laboratory findings similar to VWD - low VWF antigen, low VWF activity, prolonged bleeding time 1, 4
• Multimer analysis patterns - most commonly shows type 1 pattern (normal distribution but reduced quantity), though type 2A pattern (loss of high molecular weight multimers) occurs with shear-related mechanisms 4, 5
• Inhibitor screening - autoantibodies detected in only a minority of cases 4
• VWF:RCo/VWF:Ag ratio <0.7 - suggests functional defect when present 5

Important Clinical Pitfalls

• AVWS is frequently unrecognized or misdiagnosed as hereditary VWD - always obtain detailed personal and family bleeding history 2
• No single test proves or excludes AVWS - multiple laboratory assessments are typically required 2
• Consider AVWS testing before high-risk surgery in any patient with an AVWS-associated disorder - even without prior bleeding history 3
• Resolution of the underlying condition can normalize coagulation parameters - as demonstrated with hypothyroidism and multiple myeloma treatment 4