What is the recommended diagnosis and treatment plan for a patient with suspected Type 2 von Willebrand's (vWD) disease and a family history of abnormal bleeding?

Diagnosis and Management of Type 2 von Willebrand Disease with Family History of Abnormal Bleeding

For a patient with suspected Type 2 von Willebrand Disease (VWD) and family history of abnormal bleeding, comprehensive laboratory testing including VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), Factor VIII coagulant activity (FVIII), and VWF multimer analysis is essential for accurate diagnosis and subtyping, followed by subtype-specific treatment with either VWF-containing concentrates for Type 2A and 2B or possibly desmopressin for Type 2M. 1

Diagnostic Approach

Initial Assessment

• Conduct detailed bleeding history assessment, focusing on:
  • Prolonged bleeding after surgery, dental procedures, or trauma
  • Easy bruising
  • Frequent nosebleeds or gum bleeding
  • Heavy menstrual bleeding in female patients 1

Laboratory Testing

1. First-line tests:

   • Complete blood count (CBC) and platelet count
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (PTT) 2, 1

2. Specific VWD assays:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII) 1

3. Specialized testing for Type 2 VWD subtyping:

   • VWF multimer analysis
   • VWF:RCo/VWF:Ag ratio (ratio <0.5-0.7 suggests Type 2 VWD)
   • Ristocetin-induced platelet aggregation (RIPA)
   • Collagen binding assay 1, 3

Interpretation of Test Results for Type 2 VWD

Type 2A VWD

• VWF:RCo <30 IU/dL
• VWF:Ag 30-200 IU/dL
• VWF:RCo/VWF:Ag ratio <0.5-0.7
• Loss of high and intermediate molecular weight multimers
• Moderate to severe bleeding
• Poor response to desmopressin 1

Type 2B VWD

• VWF:RCo <30 IU/dL
• VWF:Ag 30-200 IU/dL
• VWF:RCo/VWF:Ag ratio <0.5-0.7
• Loss of high molecular weight multimers
• Enhanced RIPA at low concentrations
• Often thrombocytopenia
• Moderate bleeding 1

Type 2M VWD

• VWF:RCo <30 IU/dL
• VWF:Ag 30-200 IU/dL
• VWF:RCo/VWF:Ag ratio <0.5-0.7
• Normal multimer pattern
• Variable bleeding severity
• Variable response to desmopressin 1

Type 2N VWD

• Normal VWF:RCo and VWF:Ag
• Low FVIII:C
• Normal VWF:RCo/VWF:Ag ratio
• Reduced VWF:FVIII binding
• Clinical presentation resembles mild hemophilia A
• Joint and muscle bleeding may occur 1

Treatment Plan Based on VWD Subtype

Type 2A VWD

• VWF-containing concentrates are the treatment of choice
• Desmopressin typically ineffective 1

Type 2B VWD

• VWF-containing concentrates are the treatment of choice
• Desmopressin is contraindicated due to risk of thrombocytopenia and thrombosis 1, 4

Type 2M VWD

• Trial of desmopressin may be considered as first-line treatment
• If response is inadequate, switch to VWF-containing concentrates 1

Type 2N VWD

• Treatment approach similar to hemophilia A
• Focus on FVIII replacement 1

Family Screening

• All first-degree relatives of the patient should be screened for VWD due to its hereditary nature
• Screening should include:
  • Detailed bleeding history
  • Laboratory testing with VWF:Ag, VWF:RCo, and FVIII 1

Special Considerations

Preoperative Management

• Target VWF:RCo levels:
  • Minor procedures: ≥50 IU/dL
  • Major procedures: ≥80-100 IU/dL 1

Pregnancy Management

• Close monitoring during pregnancy is necessary
• Target VWF:RCo ≥50 IU/dL for vaginal delivery
• Target VWF:RCo ≥80 IU/dL for cesarean section 1

Common Pitfalls to Avoid

1. Relying on a single test for diagnosis

   • Multiple tests and clinical correlation are required for accurate diagnosis 1, 5

2. Ignoring borderline results

   • Mild VWD may present with borderline laboratory values but still cause significant bleeding 1

3. Overlooking pre-analytical variables

   • Sample collection, processing, and storage can significantly affect test results 5

4. Failing to consider VWD subtypes

   • Different VWD types have different clinical implications and treatment approaches 1

5. Administering desmopressin to Type 2B VWD patients

   • This can increase risk of thrombosis and is contraindicated 1, 4

Regular hematology follow-up is essential to monitor bleeding symptoms, assess treatment response, and evaluate iron status, particularly in patients with recurrent bleeding episodes 1.