Is there a difference in bleeding pattern between type 2M (type 2M von Willebrand disease) von Willebrand's disease and type 2B (type 2B von Willebrand disease) von Willebrand's disease?

Differences in Bleeding Patterns Between Type 2M and Type 2B von Willebrand Disease

Type 2B von Willebrand disease typically presents with more severe mucocutaneous bleeding and thrombocytopenia compared to type 2M, which generally has milder bleeding manifestations despite similar laboratory profiles of VWF dysfunction. 1, 2

Key Clinical Differences

Type 2B VWD

• Characterized by enhanced VWF binding to platelets (gain-of-function mutation)
• Distinctive clinical features:
  • Moderate to severe mucocutaneous bleeding
  • Thrombocytopenia that can be exacerbated by physiologic stressors like pregnancy, surgery, or infection 2
  • Epistaxis, gingival bleeding, easy bruising, and menorrhagia are common
  • Bleeding risk increases during pregnancy due to worsening thrombocytopenia

Type 2M VWD

• Characterized by decreased VWF binding to platelets (without multimer abnormalities)
• Clinical presentation:
  • Generally milder bleeding tendency compared to type 2B 3
  • No thrombocytopenia
  • Primarily mucocutaneous bleeding but typically less severe
  • More often misdiagnosed as type 1 or 2A VWD due to milder presentation 3

Laboratory Distinctions

Both subtypes show VWF functional discordance (low VWF activity/antigen ratio <0.5-0.7), but can be distinguished by:

Feature	Type 2M	Type 2B
Multimer pattern	Normal	Loss of high molecular weight multimers
RIPA test	Often normal at low-dose	Enhanced at low-dose ristocetin
Platelet count	Normal	Often decreased

The ristocetin-induced platelet agglutination (RIPA) test is particularly valuable in distinguishing these subtypes, as type 2B shows enhanced response at low concentrations of ristocetin, while type 2M shows normal or decreased response 1, 4.

Treatment Implications

The differences in bleeding patterns and pathophysiology lead to important treatment distinctions:

• Type 2M VWD:

  • May respond to desmopressin (DDAVP) in some cases 5
  • Trial testing for DDAVP response is recommended

• Type 2B VWD:

  • DDAVP is generally contraindicated or used with extreme caution due to risk of worsening thrombocytopenia 2
  • VWF-containing factor concentrates are the mainstay of treatment 1

Clinical Pearls and Pitfalls

• Common pitfall: Misdiagnosing type 2M as type 1 VWD due to similar multimer patterns 3, 6

  • Always calculate VWF:RCo to VWF:Ag ratio to detect functional discordance
  • Ratio <0.5-0.7 suggests type 2 VWD even with normal multimers

• Diagnostic challenge: Type 2B may not always present with thrombocytopenia at baseline but can develop it during stress

• Treatment consideration: While DDAVP is generally avoided in type 2B, it is sometimes used cautiously for minor bleeding in clinical practice when factor concentrates are unavailable 2

• Pregnancy management: Type 2B requires closer monitoring during pregnancy due to risk of worsening thrombocytopenia, while type 2M generally has more stable platelet counts

Understanding these differences is crucial for proper diagnosis and management, as misclassification can lead to inappropriate treatment choices and inadequate bleeding prevention.