Management of Von Willebrand Disease
Treatment Selection Based on VWD Type
For type 1 VWD with factor VIII levels >5%, desmopressin (DDAVP) 0.3 μg/kg IV diluted in 50 mL saline infused over 30 minutes is first-line therapy, administered 30 minutes prior to procedures or for bleeding episodes. 1, 2
Type 1 VWD Management
- DDAVP is the treatment of choice for type 1 VWD patients with factor VIII and VWF levels ≥10 IU/dL who demonstrate response to a test infusion 3
- Perform a test dose at diagnosis to establish individual response patterns and predict clinical efficacy during bleeding and surgery 4, 3
- DDAVP raises endogenous factor VIII and VWF three- to fivefold, transiently correcting both intrinsic coagulation and primary hemostasis defects 5
- If DDAVP is inadequate or contraindicated, switch to VWF/FVIII concentrates 1
Type 2 VWD Management
Type 2A:
- Attempt initial trial with desmopressin; if inadequate response, switch to VWF/FVIII concentrates 1
Type 2B:
- DDAVP is absolutely contraindicated due to risk of thrombocytopenia 1, 4
- Use VWF/FVIII concentrates as first-line therapy 1
- Human-derived medium-purity FVIII concentrates complexed to VWF are preferred 1
Type 2M and 2N:
- VWF/FVIII concentrates are first-line therapy 1
- DDAVP is not effective in the majority of these patients 5
Type 3 VWD Management
- DDAVP is completely ineffective due to virtually complete absence of VWF; VWF/FVIII concentrates are the only effective treatment option 1, 5
- Dose VWF/FVIII concentrates to achieve minimum 30% of plasma factor concentration 1
- For neuraxial anesthesia or procedures, target VWF activity ≥50 IU/dL 6, 1
Management of Specific Bleeding Scenarios
Heavy Menstrual Bleeding
- Tranexamic acid (TXA) is the preferred initial treatment for heavy menstrual bleeding in VWD patients 7
- TXA can be used alone or combined with hormonal contraceptives for enhanced bleeding control 7
Mucosal/Gastrointestinal Bleeding
- Initiate TXA immediately for mucosal bleeding 7
- For type 1 VWD patients with factor VIII levels >5%, add desmopressin to TXA if bleeding continues 7
Breakthrough Bleeding on DDAVP
- For patients with factor VIII levels >5% with minor bleeding, continue desmopressin at 0.3 μg/kg 8
- For patients with factor VIII levels ≤5% or significant bleeding, immediately administer bypassing agents: recombinant factor VIIa (rFVIIa) 90-120 μg/kg every 2-3 hours or activated prothrombin complex concentrates (aPCC) 50-100 IU/kg every 8-12 hours 8
- Bypassing agents are effective in 90% of bleeding episodes when used as first-line therapy 8
Alternative Treatment Options
When VWF/FVIII Concentrates Unavailable
- Cryoprecipitate can be used when VWF/FVIII concentrates are unavailable or when there is no response to desmopressin 1, 9
- Fresh frozen plasma is a viable option, though less concentrated than cryoprecipitate 9
- Virus-inactivated concentrates should be preferred over cryoprecipitate when available due to superior safety profile 5
Critical Monitoring Parameters
Pre-Treatment Assessment
- Test for von Willebrand activity before starting desmopressin in patients with bleeding history to determine specific VWD type 1, 7
- Check bleeding time, factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen during desmopressin administration to ensure adequate levels 2
Signs of Treatment Failure
- No change in blood loss over time 7, 8
- Hemoglobin decrease despite red blood cell replacement 7, 8
- Increasing dimensions of internal bleeding on imaging 7, 8
Important Safety Considerations and Contraindications
DDAVP-Specific Warnings
- Hold DDAVP 3-7 days pre- and post-surgery depending on procedure type and bleeding risk 1
- Use caution with concurrent antiplatelet agents or anticoagulants due to increased bleeding risk 1
- Monitor for water retention and hyponatremia with risk of seizures, particularly in elderly patients 8
- DDAVP is not indicated for hemophilia A with factor VIII ≤5%, hemophilia B, or patients with factor VIII antibodies 2
Adjunctive Therapy Considerations
- Use tranexamic acid as adjunctive treatment, except when combined with aPCC due to thrombotic risk 7, 8