Acquired von Willebrand Syndrome Secondary to Autoantibodies in SLE
This patient has acquired von Willebrand syndrome (AVWS) caused by autoantibodies against von Willebrand factor, a known complication of systemic lupus erythematosus, and should be treated with corticosteroids as first-line therapy, with rituximab reserved for refractory cases.
Diagnostic Reasoning
The laboratory pattern is pathognomonic for AVWS rather than congenital von Willebrand disease:
Markedly reduced VWF:Ag (19%), VWF activity (17%), and ristocetin cofactor (12%) with normal multimer distribution indicates rapid clearance of VWF-antibody complexes from circulation rather than a structural VWF defect 1, 2.
Low factor VIII activity (47%) occurs because factor VIII circulates bound to VWF; when VWF is cleared rapidly by autoantibodies, factor VIII is also depleted 2, 3.
Low IgA (118) and IgM (79) with elevated polyclonal IgG in the context of SLE suggests immune dysregulation and supports an autoantibody-mediated process 3.
The presence of SLE and Lambert-Eaton myasthenic syndrome (both autoimmune conditions) strongly supports an autoimmune etiology for the VWF deficiency 1, 2, 4.
Key Distinguishing Features from Congenital VWD
Normal multimer distribution rules out type 2A VWD (which shows loss of high-molecular-weight multimers) 2.
The severity of VWF reduction with normal multimers in an adult with autoimmune disease is characteristic of AVWS, not congenital disease 1, 4.
Congenital VWD would have presented with lifelong bleeding symptoms, not new-onset bleeding in a 50-year-old 1.
Confirmatory Testing
Perform mixing studies to detect VWF inhibitor:
Mix patient plasma 1:1 with normal pooled plasma and measure VWF:Ag levels 1, 5.
Presence of an inhibitor will cause decreased VWF:Ag in the mixture compared to expected levels 5, 3.
ELISA for anti-VWF antibodies (IgG, IgA, and IgM) can quantify the autoantibody 3, 4.
Management Algorithm
Acute Bleeding Management
Antifibrinolytics (tranexamic acid or aminocaproic acid) for mucosal bleeding 1.
Recombinant factor VIIa or activated prothrombin complex concentrate for severe bleeding unresponsive to other measures 1.
DDAVP is typically ineffective because autoantibodies rapidly clear any released VWF 2.
Factor VIII/VWF concentrates have limited efficacy due to rapid clearance by autoantibodies, though may provide transient benefit 2.
High-dose intravenous immunoglobulin (IVIG) can provide transient improvement by blocking antibody-mediated clearance 1, 2.
Definitive Treatment
First-line: Corticosteroids
High-dose prednisone (1 mg/kg/day) is the initial treatment of choice 2, 5, 4.
Treatment targets the underlying SLE and suppresses autoantibody production 2, 4.
Monitor VWF parameters (VWF:Ag, VWF:RCo, factor VIII) to assess response 4.
Expect normalization of VWF levels and multimer patterns with successful treatment 5, 4.
Second-line: Rituximab
Reserved for patients who fail corticosteroid therapy or have refractory disease 1.
Rituximab achieved complete remission in a severe type 3-like AVWS case that failed steroids and IVIG 1.
Standard dosing: 375 mg/m² weekly for 4 weeks 1.
Additional immunosuppression:
- Consider adding azathioprine, mycophenolate, or cyclophosphamide for long-term control of SLE and prevention of AVWS relapse 1, 2.
Critical Pitfalls to Avoid
Do not assume congenital VWD in an adult with new-onset bleeding and autoimmune disease—always consider AVWS 1, 4.
Do not rely solely on DDAVP or factor VIII/VWF concentrates for bleeding management, as they are typically ineffective in autoimmune AVWS 2.
Ensure aggressive treatment of underlying SLE to prevent AVWS relapse—non-compliance with immunosuppression led to fatal relapse in one reported case 1.
Monitor VWF parameters regularly during and after treatment to detect early relapse 1, 4.
Do not discontinue immunosuppression prematurely—long-term maintenance therapy is essential to prevent recurrence 1.