What are the similarities and differences between Type 2M and Type 1 von Willebrand disease (VWD) management?

Similarities and Differences Between Type 2M and Type 1 von Willebrand Disease Management

Type 2M and Type 1 von Willebrand disease (VWD) require different management approaches, with Type 2M typically requiring VWF/FVIII concentrates as first-line therapy, while Type 1 can often be managed with desmopressin. 1

Disease Characteristics

Type 1 VWD

• Quantitative deficiency of VWF 1, 2
• VWF:RCo/VWF:Ag ratio >0.5-0.7 1
• Normal multimer distribution 3
• Mild to moderate bleeding symptoms 1
• Most common type, affecting up to 1% of the population 1
• Predominantly inherited in autosomal dominant pattern 1

Type 2M VWD

• Qualitative defect in VWF function 2, 3
• VWF:RCo/VWF:Ag ratio <0.6 4, 5
• Normal multimer distribution (key distinguishing feature from other Type 2 variants) 4, 3
• Markedly defective platelet adhesion despite normal multimer structure 3
• May include collagen-binding defects in addition to platelet-binding defects 4
• Generally considered a more serious bleeding disorder than Type 1 6

Diagnostic Approach

Laboratory Testing for Both Types

• Baseline testing should include:
  • VWF:Ag (von Willebrand factor antigen)
  • VWF:RCo (ristocetin cofactor activity)
  • FVIII levels
  • Complete blood count
  • Coagulation profile 1

Distinguishing Between Types

• Key differentiating factors:
  1. VWF:RCo/VWF:Ag ratio: Type 1 typically >0.5-0.7, Type 2M typically <0.6 1, 6
  2. Platelet binding assays: Markedly decreased in Type 2M 4
  3. Ristocetin-induced platelet aggregation (RIPA): Decreased or absent in Type 2M, may be normal in mild Type 1 5
  4. Genetic testing: Different mutation patterns (e.g., Type 2M often has mutations in the A1 domain of VWF) 4, 6

Treatment Approaches

Similarities in Management

• Both require assessment of bleeding severity and specific clinical situation 1
• Both may benefit from antifibrinolytic agents as adjunctive therapy 1
• Target VWF activity level ≥50 IU/dL for acute bleeding episodes in both types 1
• Monitoring for thrombotic risk during treatment with VWF-containing concentrates 1

Differences in Management

Type 1 VWD

• Desmopressin is typically first-line therapy 1
• Good response to desmopressin in most patients 1
• May only need treatment during bleeding episodes or procedures 1

Type 2M VWD

• VWF/FVIII concentrates are typically first-line therapy 1
• Desmopressin may be less effective than in Type 1 6
• May require more aggressive prophylaxis due to higher bleeding risk 1, 6
• Typical dosing of VWF-containing concentrates: 40 IU/kg 1
• May require long-term prophylaxis in cases of severe bleeding phenotype 1

Clinical Pitfalls and Caveats

• Type 2M VWD can "masquerade" as Type 1 VWD if only basic testing is performed 6
• Both can have normal aPTT, especially in mild cases 1
• Type 2M is heterogeneous, comprising both collagen- and platelet-binding defects, which may affect treatment response 4
• Understanding the precise defect for each mutation is crucial for optimal diagnosis and treatment 4
• Type 2M may require more aggressive prophylaxis due to potentially more severe bleeding phenotype 1, 6

Management Algorithm

1. Confirm diagnosis and type:

   • Complete laboratory panel including VWF:RCo/VWF:Ag ratio and multimer analysis
   • Consider genetic testing for definitive typing

2. For Type 1 VWD:

   • Trial of desmopressin with monitoring of response
   • Reserve VWF/FVIII concentrates for non-responders or severe bleeding

3. For Type 2M VWD:

   • Primary treatment with VWF/FVIII concentrates (40 IU/kg)
   • Consider desmopressin trial only in mild cases with documented response
   • Consider long-term prophylaxis for severe bleeding phenotypes

4. For both types during acute bleeding:

   • Immediate administration of appropriate therapy to achieve VWF activity ≥50 IU/dL
   • Consider adjunctive antifibrinolytic agents
   • Monitor for thrombotic complications