What type of von Willebrand disease does a 50‑year‑old female with systemic lupus erythematosus and Lambert‑Eaton myasthenic syndrome have, given elevated IgG, negative monoclonal protein and normal IgA?

Acquired von Willebrand Syndrome (Type 2-like)

This patient has acquired von Willebrand syndrome (AVWS) associated with systemic lupus erythematosus, most likely presenting as a Type 2-like pattern with autoantibody-mediated VWF deficiency. 1, 2, 3

Diagnostic Classification

The combination of SLE with negative monoclonal protein strongly indicates autoimmune AVWS Type 2 rather than paraprotein-mediated disease. 1, 4, 3

Key Laboratory Features Expected in SLE-Associated AVWS

• Prolonged bleeding time with normal platelet count distinguishes this from thrombocytopenic bleeding 3
• Prolonged aPTT with normal PT reflects decreased factor VIII levels (mean 15% in SLE-AVWS) 4, 3
• Decreased or absent ristocetin-induced platelet aggregation (RIPA) is characteristic 4, 3
• Very low VWF:RCo (mean 6.2%) and VWF:Ag (mean 10.7%) with VWF:RCo/VWF:Ag ratio suggesting qualitative defect 4
• Type 2 multimeric pattern on VWF multimer analysis showing loss of high-molecular-weight multimers 5, 4, 3
• Detectable anti-VWF autoantibodies (usually IgG) either free or bound to VWF-factor VIII complexes 6, 4, 3

Critical Distinguishing Features from Congenital Type 3 VWD

Unlike true Type 3 VWD, platelet VWF is reduced but not completely undetectable in autoimmune AVWS. 6

• The autoantibody-antigen complex is rapidly cleared from circulation, causing acquired deficiency rather than absent synthesis 4, 3
• Some cases show abnormal multimer patterns with only two bands (low MW protomer and abnormally high MW) without intermediate multimers, resembling endothelial cell VWF 6

Pathophysiology in This Patient

The elevated IgG (467 mg/dL, flagged as abnormal) without monoclonal protein indicates polyclonal hypergammaglobulinemia typical of active SLE, which produces the anti-VWF autoantibodies. 1, 4, 3

• Neutralizing and non-neutralizing IgG anti-VWF autoantibodies bind to intermediate and high-molecular-weight VWF-factor VIII particles 4
• The bound autoantibody-antigen complex undergoes rapid clearance, resulting in quantitative and qualitative VWF deficiency 4, 3
• This mechanism explains poor response to desmopressin and VWF-factor VIII concentrates because the infused VWF is also rapidly cleared 4

Essential Confirmatory Testing

Order VWF multimer analysis immediately—this is the gold standard for confirming Type 2-like AVWS and distinguishing it from other patterns. 5, 7

• VWF:Ag, VWF:RCo, and factor VIII levels to quantify deficiency 5
• VWF:RCo/VWF:Ag ratio <0.7 confirms qualitative (Type 2-like) rather than purely quantitative defect 5, 7
• Mixing study to detect VWF inhibitor (measured in Bethesda units) 2
• Anti-VWF antibody testing if available 2, 6
• Complement levels (C3, C4, CH50) to assess SLE activity 1

Important Pre-Analytical Considerations

Avoid testing during acute SLE flare, as inflammatory response elevates VWF levels and may mask the diagnosis. 5

• Blood samples must be transported at room temperature and processed promptly 5, 8
• Stress during venipuncture can falsely elevate VWF 5

Treatment Algorithm

Step 1: Aggressive SLE Treatment (Primary Therapy)

Treat the underlying autoimmune disease first—this is the only curative approach for SLE-associated AVWS. 7, 2, 3

• Prednisone 1 mg/kg daily (maximum 80 mg) is effective in AVWS associated with autoimmune disorders 1, 3
• All reported SLE-AVWS cases were cured by appropriate immunosuppression with prednisone or other agents 3

Step 2: Rituximab for Refractory Cases

If bleeding continues despite corticosteroids, add rituximab—this has achieved normalization of VWF parameters in severe autoimmune AVWS. 1, 2

• One case report documented complete resolution after rituximab when steroids and IVIG failed 2
• Rituximab is effective for IgM-related AVWS and should be considered for IgG-mediated disease 1

Step 3: Acute Bleeding Management

For active bleeding, use a stepwise approach starting with antifibrinolytics, then escalating to bypassing agents if needed. 7, 2

• Tranexamic acid 1-1.5 g orally three times daily or 10 mg/kg IV three times daily for mucosal bleeding 7
• High-dose IVIG (1 g/kg for 2 days) provides transient correction lasting a few weeks by blocking autoantibody-mediated clearance 4, 3
• Recombinant activated factor VII (rFVIIa) 90 mcg/kg every 2-3 hours for severe bleeding unresponsive to other measures 2
• Activated prothrombin complex concentrate (aPCC) as alternative bypassing agent 2

Critical Treatment Pitfalls

Desmopressin and VWF-factor VIII concentrates have major limitations in autoimmune AVWS because infused VWF is rapidly cleared by circulating autoantibodies. 7, 4, 3

• Poor response to desmopressin with shortened half-life times for factor VIII and VWF 4, 3
• VWF concentrates are ineffective as monotherapy without treating the underlying autoimmune process 4

Lambert-Eaton Myasthenic Syndrome Considerations

The coexistence of LEMS does not directly cause AVWS but indicates aggressive autoimmune disease requiring comprehensive immunosuppression. 2

• LEMS is associated with voltage-gated calcium channel antibodies, representing a separate autoimmune phenomenon 2
• This emphasizes the importance of aggressive initial SLE therapy to reduce secondary autoimmune complications 2

Monitoring Requirements

Repeat VWF:RCo, VWF:Ag, and factor VIII levels every 2-4 weeks during treatment to assess response. 8, 7

• Multimer analysis should normalize with successful immunosuppression 2, 6
• Monitor for relapse if immunosuppression is discontinued—one case relapsed two years later due to medication non-compliance 2
• Continued treatment of the underlying SLE is essential to prevent AVWS recurrence 2

Prognosis and Long-Term Management

With appropriate immunosuppression, the anti-VWF antibody disappears and hemostatic profile normalizes, though platelet VWF content may remain decreased. 6

• Maintain SLE remission with ongoing immunosuppression 2, 3
• Frequent patient monitoring and medication compliance are critical—the reported fatal case died from sepsis and uremic complications after stopping immunosuppression 2