What is the management of Von Willebrand disease?

Management of Von Willebrand Disease

Desmopressin (0.3 μg/kg IV) is the first-line treatment for Type 1 VWD patients with VWF levels >10 IU/dL who demonstrate responsiveness on test infusion, while VWF/FVIII concentrates are required for Type 2 and Type 3 disease or when desmopressin fails. 1, 2, 3

Treatment Selection by VWD Type

Type 1 VWD (75% of cases)

• Desmopressin is the treatment of choice for Type 1 patients with factor VIII and VWF levels ≥10 IU/dL 3
• Administer 0.3 μg/kg IV (maximum 28 μg) 30 minutes prior to procedures or for acute bleeding 1, 2
• Desmopressin stimulates endothelial release of stored VWF, increasing circulating VWF and factor VIII levels 3-6 fold within 30-90 minutes 1
• Mandatory test infusion required before relying on desmopressin to confirm individual responsiveness 3
• Doses may be repeated at 12-24 hour intervals, but tachyphylaxis occurs after 3-5 doses due to endothelial VWF store depletion 1

Type 2 VWD (Qualitative Defects)

• VWF/FVIII concentrates are the primary treatment as desmopressin is ineffective in most Type 2 variants 4, 3
• Plasma-derived concentrates containing both VWF and factor VIII should be used 4
• Maintain VWF activity >50 IU/dL during procedures and the postoperative period 1

Type 3 VWD (Severe Deficiency)

• VWF/FVIII concentrates are mandatory due to virtually complete VWF deficiency 3
• Desmopressin is contraindicated as there are no endothelial VWF stores to release 2, 4
• These patients require the most aggressive replacement therapy due to severe, life-threatening bleeding risk 5

Perioperative Management

Surgical Procedures

• Maintain VWF activity levels ≥50 IU/dL throughout the procedure and postoperative period 1
• Administer treatment 30 minutes prior to scheduled procedures 2
• For neuraxial anesthesia specifically, VWF activity must be maintained at ≥50 IU/dL using desmopressin, VWF/FVIII concentrates, or cryoprecipitate 1
• Combine with tranexamic acid (antifibrinolytic) as appropriate for enhanced hemostasis 1

Specific Bleeding Scenarios

Epistaxis (Nosebleeds)

• Apply firm sustained compression to the lower third of the nose for ≥5 minutes as first-line management 6
• If bleeding continues, apply topical vasoconstrictors 6
• Critical pitfall to avoid: Never use non-resorbable nasal packing in VWD patients as removal triggers additional bleeding 1, 6
• Use only resorbable nasal packing if packing becomes necessary 6

Spontaneous or Trauma-Induced Bleeding

• Desmopressin effectively stops bleeding from hemarthroses, intramuscular hematomas, or mucosal bleeding in responsive Type 1 patients 2
• VWF/FVIII concentrates are required for Type 2 and 3 patients with similar bleeding episodes 2

Adjunctive Therapies

• Antifibrinolytic agents (tranexamic acid) should be combined with primary treatment for enhanced hemostasis 1, 4
• Platelet concentrates may be used as adjunctive treatment when bleeding time correction is inadequate despite VWF replacement 4

Acquired Von Willebrand Syndrome (AVWS)

• Requires a multidisciplinary approach with minimization of anticoagulation and blood product replacement 1
• For refractory bleeding, use desmopressin, VWF-containing concentrates, or drugs preventing VWF proteolysis to restore high molecular weight VWF multimers 1
• Prognosis depends on treating the underlying condition causing acquired VWF deficiency 1

Monitoring Requirements

• Check bleeding time, factor VIII coagulant activity, ristocetin cofactor activity, and VWF antigen during desmopressin administration to ensure adequate levels 2
• Verify therapeutic targets are achieved before and during procedures 2

Critical Contraindications and Limitations

• Do not use desmopressin in hemophilia A patients with factor VIII levels ≤5%, hemophilia B, or patients with factor VIII antibodies 2
• Do not use desmopressin in severe homozygous VWD with factor VIII coagulant activity and VWF antigen <1% 2
• Desmopressin is contraindicated when there is evidence of abnormal molecular forms of factor VIII antigen 2