What is the approach to managing a patient with von Willebrand disease?

Management of Von Willebrand Disease

The optimal approach to managing von Willebrand disease (VWD) involves initial clinical and laboratory assessment followed by type-specific treatment, with desmopressin as first-line therapy for mild to moderate Type 1 VWD and factor concentrates for Type 2B, Type 3, and severe Type 1 VWD. 1

Initial Clinical Evaluation

• Assess for bleeding symptoms:

  • Epistaxis frequency and severity
  • Bruising patterns
  • Bleeding after minor wounds
  • Oral cavity bleeding
  • Gastrointestinal bleeding
  • Post-surgical bleeding
  • Menorrhagia in females
  • Family history of bleeding disorders

• Physical examination should evaluate:

  • Ecchymoses, hematomas, petechiae
  • Evidence of liver disease
  • Splenomegaly
  • Joint and skin laxity
  • Telangiectasia
  • Signs of anemia
  • Anatomic lesions on gynecologic examination

• Document medication use that can affect hemostasis:

  • Anticoagulants
  • NSAIDs
  • Certain supplements

Laboratory Diagnosis

• Initial laboratory tests when VWD is suspected:

  • Complete blood count (CBC)
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (PTT)

• Core VWD-specific tests:

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

• Calculate VWF:RCo to VWF:Ag ratio:

  • Ratio <0.5-0.7 suggests qualitative VWD (Type 2)

• Consider repeat testing (up to 3 times) as VWF levels can vary

• Advanced testing for complex cases:

  • Multimer analysis
  • Genetic testing
  • RIPA (ristocetin-induced platelet aggregation)

VWD Classification and Diagnostic Features

• Type 1 (70-80% of cases): Partial quantitative deficiency

  • VWF:Ag and VWF:RCo proportionally reduced
  • Normal VWF:RCo/VWF:Ag ratio (>0.7)
  • Normal multimer pattern

• Type 2 (15-20% of cases): Qualitative defects

  • Type 2A: VWF:RCo <30 IU/dL, VWF:Ag 30-200 IU/dL, VWF:RCo/VWF:Ag <0.5-0.7, Loss of high & intermediate MW multimers
  • Type 2B: VWF:RCo <30 IU/dL, VWF:Ag 30-200 IU/dL, VWF:RCo/VWF:Ag <0.5-0.7, Loss of high MW multimers, Enhanced RIPA at low-dose
  • Type 2M: VWF:RCo <30 IU/dL, VWF:Ag 30-200 IU/dL, VWF:RCo/VWF:Ag <0.5-0.7, Normal multimer pattern
  • Type 2N: Normal VWF:RCo and VWF:Ag, Low FVIII:C, Normal VWF:RCo/VWF:Ag ratio, Reduced VWF:FVIII binding

• Type 3 (Rare): Complete deficiency

  • VWF:Ag and VWF:RCo virtually absent
  • FVIII levels typically <10%

Treatment Approach

Desmopressin (DDAVP)

• First-line treatment for Type 1 VWD with factor VIII levels >5% 1, 2
• Administration options:
  • Intravenous: 0.3 μg/kg
  • Intranasal: 150 μg per nostril
  • Subcutaneous: alternative to IV route
• Mechanism: Promotes release of VWF and FVIII from endothelium
• Efficacy: Increases factor levels 3-5 fold for 8-12 hours 3
• Monitor response with VWF:RCo, FVIII:C levels
• Contraindications/Cautions:
  • Not effective in Type 3 VWD
  • Generally contraindicated in Type 2B (may worsen thrombocytopenia)
  • Use with caution in patients with cardiovascular disease
  • Risk of hyponatremia with fluid overload
  • Tachyphylaxis with repeated doses

VWF-Containing Factor Concentrates

• Indicated for:
  • Type 2B VWD
  • Type 3 VWD
  • Severe Type 1 VWD
  • When DDAVP is ineffective or contraindicated
  • Major surgery
• Dosing targets:
  • Surgical procedures: VWF activity ≥50 IU/dL
  • Major surgery: Maintain VWF:RCo >50 IU/dL for 72 hours post-surgery
  • Vaginal delivery: VWF:RCo ≥50 IU/dL
  • Cesarean section: VWF:RCo ≥80 IU/dL

Adjunctive Treatments

• Antifibrinolytics (e.g., tranexamic acid, epsilon aminocaproic acid):
  • Useful for mucosal bleeding
  • Can be used with DDAVP or factor concentrates
• Hormonal therapy for menorrhagia:
  • Combined oral contraceptives
  • Levonorgestrel-releasing intrauterine device

Special Considerations

Pregnancy Management

• VWF levels typically increase during pregnancy
• Close monitoring throughout pregnancy
• Prepare delivery plan with hematology consultation
• Target VWF:RCo ≥50 IU/dL for vaginal delivery
• Target VWF:RCo ≥80 IU/dL for cesarean section

Surgical Management

• Preoperative hematology consultation
• DDAVP trial before elective procedures in Type 1 VWD
• Factor concentrate for major surgery
• Monitor VWF:RCo and FVIII:C levels at 12-24 hours post-surgery
• Maintain VWF:RCo >50 IU/dL for 72 hours after major surgery

Common Pitfalls and Caveats

• Medication interactions: Avoid concomitant use of drugs that increase bleeding risk (NSAIDs, aspirin)
• Tachyphylaxis: Repeated DDAVP doses may lead to diminished response
• Fluid restriction: Important with DDAVP to prevent hyponatremia, especially in children
• Misdiagnosis: VWF levels can be affected by stress, exercise, pregnancy, hormonal status
• Thrombosis risk: Balance hemostasis with thrombosis risk, especially in older patients
• Acquired VWD: Consider in patients with abnormal VWF tests without personal/family history of bleeding