What is the treatment approach for a patient with Von Willebrand disease?

Treatment of Von Willebrand Disease

Desmopressin (DDAVP) is the first-line treatment for Type 1 VWD, administered intravenously at 0.3 μg/kg (maximum 28 μg), which increases VWF and factor VIII levels 3-6 fold within 30-90 minutes. 1

Initial Treatment Selection by VWD Type

Type 1 VWD (Partial Quantitative Deficiency)

• Desmopressin is the treatment of choice because it effectively corrects VWF/FVIII levels and prolonged bleeding time in the majority of Type 1 patients 2
• Administer 0.3 μg/kg IV (maximum 28 μg), with response occurring within 30-90 minutes 1
• Document response with pre- and post-treatment VWF and FVIII levels to confirm efficacy in individual patients 3
• Doses may be repeated at 12-24 hour intervals, but tachyphylaxis occurs after 3-5 doses due to depletion of endothelial VWF stores 1

Type 2 VWD (Qualitative Defects)

• VWF concentrates (plasma-derived or recombinant) are required for most Type 2 variants because desmopressin is ineffective for qualitative defects 2, 4
• Type 2B VWD is an absolute contraindication to desmopressin because it induces platelet aggregation and can worsen thrombocytopenia 5
• Target VWF activity ≥50 IU/dL for procedures and bleeding episodes 1, 3

Type 3 VWD (Complete VWF Absence)

• VWF concentrates are mandatory due to virtual absence of VWF and severe bleeding diathesis 2
• Desmopressin is ineffective in Type 3 patients 2
• These patients require higher and more frequent dosing due to complete deficiency 4

Perioperative Management

Target VWF Levels

• Maintain VWF activity ≥50 IU/dL for the duration of surgery and the entire postoperative period 1, 3
• For neuraxial anesthesia, VWF activity must be ≥50 IU/dL before procedure and maintained >50 IU/dL while epidural catheter remains in place 1, 3

Monitoring Strategy

• Monitor VWF:RCo, VWF:Ag, and FVIII levels pre-treatment, immediately post-treatment, and periodically during treatment 3
• Do not rely solely on FVIII levels—VWF activity is the critical parameter for treatment decisions 3

Adjunctive Therapies

Antifibrinolytic Agents

• Tranexamic acid is highly effective for mucosal bleeding and should be combined with desmopressin or VWF concentrates as appropriate 1, 6
• Particularly useful for persistent mucosal bleeding despite adequate FVIII levels 3

Hormonal Therapy for Women

• Hormonal contraceptives are effective for managing heavy menstrual bleeding in women with VWD 6, 4
• Interdisciplinary management is required for childbirth with prophylaxis in the postpartum period to reduce hemorrhage risk 6

Critical Safety Considerations with Desmopressin

Hyponatremia Risk

• Fluid restriction is mandatory when using desmopressin to prevent water intoxication and hyponatremia 5
• Particular caution is required in pediatric and geriatric patients who should have fluid intake adjusted downward 5
• Monitor for warning signs: headache, nausea/vomiting, decreased serum sodium, weight gain, confusion, seizures 5

Contraindications

• Absolute contraindication in Type 2B VWD due to risk of platelet aggregation 5
• Use with extreme caution in patients with habitual or psychogenic polydipsia 5

Acquired Von Willebrand Syndrome (AVWS)

ECMO-Associated AVWS

• AVWS develops within hours of ECMO initiation and persists throughout support but resolves rapidly after weaning 1
• Management requires a multidisciplinary approach with minimization of anticoagulation and blood product replacement 1
• Data supporting VWF concentrate use to prevent bleeding in ECMO patients remain limited, highlighting need for caution 1
• For refractory bleeding, targeted treatments include desmopressin, VWF concentrates, or drugs preventing VWF proteolysis 1

General AVWS Management

• Prognosis depends on the underlying condition—treatment of the underlying disorder may resolve the acquired VWF deficiency 1
• Consider AVWS in patients with aortic stenosis, lymphoproliferative disorders, or monoclonal gammopathies 7

Common Pitfalls to Avoid

• Never use non-resorbable nasal packing in VWD patients with nosebleeds 1
• Do not rely on a single test result—VWF:RCo assay has high coefficient of variation (10-30%) and repeat testing may be necessary 7
• Avoid testing during acute illness, pregnancy, or stress as these elevate VWF levels and can mask diagnosis 7
• Elevated FVIII with normal VWF activity (>50 IU/dL) generally does not require additional treatment for hemostasis 3
• If VWF activity is low despite elevated FVIII, focus treatment on correcting VWF deficiency, not FVIII 3