What are the treatment options for a patient with Von Willebrand disease?

Treatment of Von Willebrand Disease

The primary treatment options for von Willebrand disease include desmopressin (DDAVP), von Willebrand factor replacement concentrates, antifibrinolytic agents, and hormone therapy for menstrual bleeding, with selection based on VWD type, bleeding severity, and clinical scenario. 1, 2

First-Line Treatment Selection by VWD Type

Desmopressin (DDAVP)

• Desmopressin is the preferred first-line treatment for Type 1 VWD and some Type 2A patients by stimulating release of stored VWF from endothelial cells, increasing circulating VWF and factor VIII levels 3-6 fold within 30-90 minutes 1
• Standard intravenous dosing is 0.3 μg/kg (maximum 28 μg), with doses repeated at 12-24 hour intervals as needed 1
• Critical limitation: tachyphylaxis occurs after 3-5 doses due to depletion of endothelial VWF stores, requiring switch to VWF concentrates if additional treatment needed 1
• Desmopressin is not effective for Type 3 VWD (no endogenous VWF to release) and contraindicated in Type 2B VWD (can worsen thrombocytopenia) 3, 4

VWF Replacement Concentrates

• Recombinant VWF (VONVENDI) is FDA-approved for adults ≥18 years for on-demand bleeding treatment, perioperative management, and routine prophylaxis in severe Type 3 VWD 2
• For acute bleeding episodes: initial dose 40-80 IU/kg based on severity 2
  • Minor bleeding: 40-50 IU/kg, repeat every 8-24 hours as needed 2
  • Major bleeding: 50-80 IU/kg initially, then 40-60 IU/kg every 8-24 hours for 2-3 days 2
• First dose must be co-administered with recombinant factor VIII if baseline FVIII levels are <40% or unknown, as VWF concentrates alone may not immediately correct FVIII deficiency 2

Perioperative Management

Pre-Surgical Planning

• For elective surgery, administer VWF 12-24 hours pre-operatively to allow endogenous FVIII levels to rise to ≥30 IU/dL (minor surgery) or ≥60 IU/dL (major surgery) 2
• Assess FVIII:C levels within 3 hours before surgery to determine if additional recombinant FVIII is needed 2
• Target VWF:RCo levels: 50-60 IU/dL for minor surgery, 100 IU/dL for major surgery 2
• Target FVIII:C levels: 40-50 IU/dL for minor surgery, 80-100 IU/dL for major surgery 2

Intraoperative and Postoperative Management

• Maintain VWF activity ≥50 IU/dL throughout the procedure and postoperative period, particularly for neuraxial anesthesia 1
• Very-low-certainty evidence suggests maintaining FVIII or VWF levels >50 IU/dL for at least 3 consecutive days after major surgery achieves excellent hemostatic efficacy in 74-100% of cases 5
• Continuous monitoring of VWF:RCo and FVIII:C plasma levels is mandatory postoperatively to guide additional dosing 2

Adjunctive Therapies

Antifibrinolytic Agents

• Tranexamic acid combined with VWF replacement reduces bleeding complications more effectively than VWF replacement alone for minor procedures (low to very-low-certainty evidence) 5
• Particularly useful for mucosal bleeding (epistaxis, dental procedures, menorrhagia) 3, 4

Hormone Therapy for Women

• Hormonal contraceptives or hormone therapy are effective for managing heavy menstrual bleeding in women with VWD 3, 4
• Should be used in combination with standard VWD treatments as needed 4

Prophylactic Therapy

Routine Prophylaxis for Severe Type 3 VWD

• Initial dosage: 40-60 IU/kg VONVENDI twice weekly for patients with severe Type 3 VWD experiencing frequent breakthrough bleeding on on-demand therapy 2
• Dose may be adjusted up to 60 IU/kg twice weekly based on bleeding frequency 2

Special Clinical Scenarios

Acquired Von Willebrand Syndrome (AVWS)

• AVWS requires multidisciplinary approach including minimizing anticoagulation and blood product replacement 1
• For refractory bleeding, targeted treatments include desmopressin, VWF-containing concentrates, or drugs preventing VWF proteolysis 1
• In ECMO patients, AVWS develops within hours and persists throughout ECMO support, but resolves rapidly after weaning 6
• Data supporting VWF concentrate use to prevent bleeding in ECMO patients remain limited 6

Critical Safety Considerations

Thromboembolic Risk

• Thromboembolism can occur with VWF replacement, particularly in patients with pre-existing risk factors 2
• Monitor for early thrombosis signs and institute prophylactic measures according to current recommendations 2
• One of 100 VWD subjects in clinical trials developed proximal deep vein thrombosis perioperatively after total hip replacement 2

Product Storage and Administration

• Reconstituted VONVENDI must be used immediately or within 3 hours at room temperature ≤25°C (77°F) 2
• Store unreconstituted product refrigerated at 2-8°C or room temperature ≤30°C 2

Common Pitfalls to Avoid

• Do not use non-resorbable nasal packing in VWD patients with epistaxis 1
• Do not rely on desmopressin alone for Type 3 VWD or Type 2B VWD 3, 4
• Do not administer VWF concentrates without checking baseline FVIII levels - may need concurrent recombinant FVIII 2
• Do not assume bleeding control without laboratory confirmation - monitor VWF:RCo and FVIII:C levels to guide therapy 2