What is the management approach for von Willebrand disease?

Management of Von Willebrand Disease

The management of von Willebrand disease (VWD) should be tailored according to disease subtype, with desmopressin as first-line treatment for mild to moderate Type 1 VWD and VWF-containing factor concentrates for Type 2B, Type 3, and severe forms of Type 1 and 2 VWD. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification are essential:

• Use standardized bleeding assessment tools (BAT) to objectively quantify bleeding history

• Initial laboratory testing should include:

  • VWF antigen (VWF:Ag)
  • VWF activity (VWF:RCo)
  • Factor VIII coagulant activity (FVIII:C)
  • Calculation of VWF:RCo/VWF:Ag ratio

• Consider specialized studies (multimer analysis, genetic testing) when bleeding history is strong but initial tests are normal 1

• Repeat testing up to 3 times as VWF levels can vary

Treatment Approach by VWD Type

Type 1 VWD (70-80% of cases)

• First-line treatment: Desmopressin (DDAVP) 1, 2
  • Raises endogenous factor VIII and VWF 3-5 fold 3
  • Corrects both intrinsic coagulation and primary hemostasis defects
  • Most effective when FVIII and VWF levels are >5% 2
  • Administer 30 minutes prior to scheduled procedures 2

Type 2 VWD

• Most Type 2 variants (especially 2B) do not respond well to desmopressin 1
• Treatment of choice: VWF-containing factor concentrates
• Note: Desmopressin is contraindicated in Type 2B as it can induce thrombocytopenia 4

Type 3 VWD

• Desmopressin is ineffective 3, 5
• Treatment of choice: VWF-containing factor concentrates

Specific Treatment Options

Desmopressin (DDAVP)

• Dosing: 0.3 μg/kg intravenously
• Perform a test dose before therapeutic use to assess individual response 1, 4
• Monitor VWF:RCo and FVIII:C levels
• Caution: Avoid in patients with Type 2B VWD due to risk of thrombocytopenia 4

VWF-containing Factor Concentrates

• Indicated for:
  • Severe Type 1 VWD
  • Most Type 2 VWD cases
  • All Type 3 VWD cases
  • When desmopressin is ineffective or contraindicated 1
• Virus-inactivated concentrates are preferred over cryoprecipitate for safety 3

Perioperative Management

• Target VWF activity level of ≥50 IU/dL for surgical procedures 1
• 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
  • Consider cell salvage techniques
  • Maintain normothermia and avoid hypotension

Management During Pregnancy and Childbirth

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

Adjunctive Treatments

• Antifibrinolytic agents (e.g., tranexamic acid) can be used as adjunctive therapy
• For patients with poor correction of bleeding time despite primary treatment, consider:
  • Additional desmopressin doses (with caution for tachyphylaxis)
  • Platelet concentrates in severe cases 6

Important Considerations and Pitfalls

• Avoid concomitant use of aspirin or other platelet antiaggregants with metoclopramide as this may worsen platelet dysfunction 1
• Balance hemostasis with thrombosis risk, especially in older patients
• Document response to interventions to guide future management
• Fresh frozen plasma and cryoprecipitate remain viable options in resource-limited settings 7
• For patients with acquired von Willebrand syndrome, avoid metoclopramide 1

Special Situations

• For patients with factor VIII levels between 2-5%, desmopressin may be tried but requires careful monitoring 2
• For patients with antibodies to VWF, specialized management is required
• In developing countries where factor concentrates may be unavailable, fresh frozen plasma and cryoprecipitate are acceptable alternatives 7