Do patients with Type 2 von Willebrand disease (VWD) also show delayed bleeding?

Type 2 von Willebrand Disease and Delayed Bleeding

Yes, patients with Type 2 von Willebrand disease (VWD) can experience delayed bleeding, particularly following trauma or surgical procedures, which is why the European Hematology Association recommends continuing factor replacement for at least 7-14 days post-trauma due to this risk. 1

Clinical Characteristics of Type 2 VWD

Type 2 VWD encompasses qualitative abnormalities of von Willebrand factor (VWF) structure and function, resulting in variable bleeding tendencies. It is characterized by:

• Prolonged bleeding time
• Low VWF:ristocetin cofactor activity (RCo)/antigen concentration (Ag) ratios
• Absence of high molecular weight VWF multimers
• Normal prothrombin time (PT) but potentially prolonged activated partial thromboplastin time (aPTT) in severe cases 1, 2

Subtypes of Type 2 VWD

Type 2 VWD is divided into four main subtypes, each with distinct characteristics:

1. Type 2A: Most common subtype, characterized by decreased platelet-dependent VWF function due to absence of high and intermediate molecular weight VWF multimers

   • Can be further classified into Group I (severe) and Group II (mild) 2

2. Type 2B: Features increased affinity of VWF for platelet GPIbα receptors, causing thrombocytopenia and preferential loss of high molecular weight VWF multimers 3

3. Type 2M: Characterized by decreased VWF-platelet interactions despite normal multimer distribution

4. Type 2N: Features decreased binding of VWF to factor VIII, mimicking mild hemophilia A 1, 4

Delayed Bleeding in Type 2 VWD

The risk of delayed bleeding in Type 2 VWD is significant enough that:

• The European Hematology Association recommends continuing factor replacement for 7-14 days post-trauma 1
• Close monitoring is advised for at least 2 weeks post-procedure 1
• For surgical procedures, maintaining factor levels above 100 IU/dL during surgery and for 7-10 days postoperatively is recommended 1

This delayed bleeding risk is particularly important in:

• Post-surgical settings
• Following trauma
• Dental procedures
• Childbirth

Management Considerations

Treatment approaches for Type 2 VWD should consider the risk of delayed bleeding:

• Desmopressin (DDAVP): May be useful in some Type 2 variants, particularly Type 2M with nearly normal multimeric patterns, but response is often transient and incomplete 5

  • Should be avoided in Type 2B due to risk of worsening thrombocytopenia 3
  • A trial test should be performed in all Type 2 VWD patients except Type 2B 5

• VWF/FVIII concentrates: Represent the mainstay of treatment, particularly for:

  • Patients not responding to desmopressin
  • Those requiring sustained hemostatic correction for major surgery or bleeding
  • Immediate administration with target VWF activity ≥50 IU/dL is recommended 1, 5

• Prophylaxis: Long-term prophylaxis with VWF/FVIII concentrates may be necessary for patients with:

  • Recurrent joint bleeds
  • Frequent gastrointestinal bleeding
  • Severe epistaxis causing anemia 1, 6

Important Clinical Pitfalls

1. Misdiagnosis: Type 2 VWD can be misdiagnosed due to variable clinical presentations and laboratory findings, even among patients with identical mutations 3

2. Desmopressin caution: In Type 2B VWD, desmopressin may cause a transient decrease in platelet count, potentially increasing bleeding risk 3

3. Inadequate treatment duration: Failure to continue factor replacement for sufficient duration post-procedure may result in delayed hemorrhage 1

4. Monitoring limitations: Standard coagulation tests may not accurately reflect bleeding risk in Type 2 VWD, as PT is typically normal and aPTT may be normal in milder cases 1

5. Suboptimal platelet transfusion: In Type 2B VWD, platelet transfusions may provide suboptimal results as transfused platelets may be aggregated by the patient's abnormal VWF 3