Introduction
Wilate is a human plasma-derived, double virus inactivated, freeze-dried concentrate containing von Willebrand factor (VWF) and coagulation factor VIII (FVIII) in a physiological ratio. It is specifically formulated for the treatment of von Willebrand disease (VWD), a hereditary bleeding disorder characterized by quantitative or qualitative deficiencies in VWF. Wilate provides comprehensive replacement therapy by addressing both the primary defect in VWD and the secondary FVIII deficiency that results from inadequate VWF protection.
Mechanism of Action
Wilate works through two complementary mechanisms. The von Willebrand factor component promotes platelet adhesion to damaged vascular endothelium and serves as a carrier protein for factor VIII, protecting it from rapid proteolytic degradation. The factor VIII component acts as an essential cofactor in the intrinsic pathway of the coagulation cascade, accelerating the conversion of factor X to factor Xa, which ultimately leads to thrombin generation and fibrin clot formation. The physiological 1:1 ratio of VWF:FVIII in Wilate ensures appropriate stabilization and function of both proteins.
Indications
Wilate is FDA-approved for:
- Treatment of spontaneous and trauma-induced bleeding episodes in adults and children with von Willebrand disease
- Perioperative management of bleeding in patients with von Willebrand disease
- Routine prophylaxis to prevent bleeding episodes in patients with severe von Willebrand disease
It is particularly effective for types 1 and 2 VWD, and may be used in type 3 VWD when desmopressin is ineffective or contraindicated.
Dosage and Administration
Standard dosing: Based on VWF:RCo (ristocetin cofactor) units- Minor bleeding: 40-60 IU VWF:RCo/kg body weight
- Moderate bleeding: 40-50 IU VWF:RCo/kg body weight, may require repeat doses
- Severe bleeding: 50-75 IU VWF:RCo/kg body weight
- Surgery: 50-75 IU VWF:RCo/kg body weight preoperatively
- Reconstitute with provided sterile water for injection
- Administer by intravenous infusion at a rate not exceeding 4 mL/minute
- Dosage frequency varies based on bleeding severity and clinical response (typically every 8-24 hours)
- Pediatric patients: Dose based on body weight
- Elderly patients: No specific dosage adjustment required
- Renal/hepatic impairment: Use with caution; monitor response carefully
Pharmacokinetics
Absorption: Administered intravenously, achieving immediate bioavailability Distribution: VWF distributes primarily within the vascular compartment; FVIII follows VWF distribution Metabolism: Cleared via specific receptors (mainly macrophages and endothelial cells) Elimination: Biphasic elimination pattern- Initial half-life (VWF:Ag): 6-20 hours
- Terminal half-life (VWF:RCo): 8-12 hours
- FVIII half-life: 12-15 hours (prolonged due to VWF stabilization)
Contraindications
- Known hypersensitivity to Wilate or any of its components
- History of anaphylactic reactions to human plasma-derived products
- Patients with known hypersensitivity to mouse proteins (trace amounts may be present)
Warnings and Precautions
Thromboembolic risk: Monitor for signs of thrombosis, particularly in patients with known risk factors Allergic reactions: May occur; have appropriate medications and equipment available Neutralizing antibodies: Monitor for development of inhibitors to VWF or FVIII Transmissible infectious agents: Despite viral inactivation steps, theoretical risk remains Renal dysfunction: Use with caution in patients with pre-existing renal conditions Hyperfibrinogenemia: May occur with repeated administrationsDrug Interactions
- Antifibrinolytic agents (tranexamic acid, aminocaproic acid): May increase thrombotic risk
- Combined hormonal contraceptives: May affect VWF and FVIII levels
- Selective serotonin reuptake inhibitors: May affect platelet function
- Anticoagulants and antiplatelet agents: May reduce efficacy of Wilate
Adverse Effects
Common (≥1%):- Headache
- Dizziness
- Nausea
- Flushing
- Injection site reactions
- Anaphylactic reactions
- Thrombotic events
- Development of inhibitors to VWF or FVIII
- Hemolytic reactions
- Transmission of infectious agents
Monitoring Parameters
Before administration:- VWF:RCo and FVIII levels
- Bleeding assessment
- Vital signs
- Clinical bleeding response
- VWF:RCo and FVIII activity levels (target: 50-100% for minor bleeding, 100% for major bleeding/surgery)
- Signs of allergic reactions
- Thrombotic complications
- Inhibitor development (every 3-6 months or if clinical response decreases)
- Iron status (chronic blood loss)
- Joint health (repeated hemarthroses)
Patient Education
- Recognize signs and symptoms of bleeding requiring treatment
- Understand proper storage and handling of medication
- Report any adverse reactions immediately
- Carry medical identification indicating VWD diagnosis
- Inform all healthcare providers about VWD and Wilate use
- Understand importance of regular follow-up and monitoring
- Recognize signs of thrombosis (unusual swelling, pain, redness)
- Report decreased response to treatment promptly
References
1. Mannucci PM. Treatment of von Willebrand disease. N Engl J Med. 2004;351(7):683-694. 2. FDA Prescribing Information: Wilate. October 2020. 3. Berntorp E, et al. Wilate®: a von Willebrand factor concentrate with a low content of active FVIII. Haemophilia. 2010;16(2):296-305. 4. Laffan MA, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol. 2014;167(4):453-465. 5. Leebeek FWG, Eikenboom JCJ. Von Willebrand's disease. N Engl J Med. 2016;375(21):2067-2080. 6. Abshire T, et al. Prophylaxis in severe forms of von Willebrand disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN). Haemophilia. 2013;19(1):76-81.