octapharma
For the treatment of VWD

wilate®: von Willebrand Factor (VWF) Structure

VWF structure compared to human plasma

Triplet structure: von willebrand factor (VWF) is present in plasma in the form of various large molecules called VWF multimers. Each individual multimer band consists of three bands that form a triplet. The subbands are of different intensity. Typically in a normal circulating VWF, there is a more pronounced central band (A) and two weaker satellite bands (B, C). A modified abnormal triplet pattern indicates increased breakdown of the VWF.1,2

wilate® demonstrated a physiologic triplet structure and multimeric distribution.3

Multimer analysis showing triplet structure of wilate® and Humate-P® compared to standard human plasma (SHP)4

Multimeric analysis4

  • wilate® and Humate-P® demonstrated similar multimer profiles
  • Slightly reduced levels of high-molecularweight (HMW) multimers vs control plasma over time
  • wilate® showed an intact triplet structure similar to control plasma
  • Disruption of the native VWF triplet structure was observed with Humate-P®
  • The functional significance and clinical impact of this needs further study

 

Distribution of wilate® triplet bands in %3

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Relative contents of VWF multimer satellite band 3 of NP and wilate®. The left-hand bars each represent the slow migrating satellite bands, the middle bars represent the central bands, and the right-hand bars represent  the fast migrating bands.

 

Platelet binding under flow conditions

In a human body, VWF has to exert its haemostatic function under flow conditions. Octapharma is performing VWF studies not only under static conditions but also in a shear rate environment mimicking the physiologic conditions of a blood flow. These experiments clearly demonstrate the ability of wilate® to mediate platelet binding to collagen under shear stress, as found in the vascular system.5

VWF-mediated platelet binding to collagen under physiologic flow conditions

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Platelet binding to collagen III without
substitution of VWF
Platelet binding to collagen III with 1 IU/mL wilate®

Flow conditions (1700 s-1, simulating arterial flow conditions) in presence of washed red blood cells.

 

Indications and Usage

wilate® is a von Willebrand Factor/Coagulation Factor VIII Complex (Human) indicated in children and adults with von Willebrand disease for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding. wilate® is not indicated for the treatment of hemophilia A.

Important Safety Information

wilate® is contraindicated for patients who have known anaphylactic or severe systemic reaction to plasma-derived products, any ingredient in the formulation, or components of the container.

Hypersensitivity or allergic reactions have been observed upon use of wilate® and may in some cases progress to severe anaphylaxis (including shock) with or without fever.

When using a factor VIII (FVIII)-containing von Willebrand Factor (VWF) product, the treating physician should be aware that continued treatment may cause excessive rise in FVIII activity. Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate® to avoid sustained excessive VWF and FVIII activity levels, which may increase the risk of thrombotic events.

Patients with VWD, especially type 3 patients, may potentially develop neutralizing antibodies (inhibitors) to VWF, manifesting as an inadequate clinical response. Since inhibitor antibodies may occur concomitantly with anaphylactic reactions, patients experiencing an anaphylactic reaction should also be evaluated for the presence of inhibitors.

wilate® is made from human plasma. As with all plasma-derived products, the risk of transmission of infectious agents, eg, viruses and, theoretically, the variant Creutzfeldt-Jakob disease (vCJD) agent or other unknown infectious agents, cannot be completely eliminated. Despite measures to reduce this risk, such products may still potentially transmit disease.

The most common adverse reactions to treatment with wilate® in patients with VWD have been urticaria and dizziness. The most serious adverse reactions to treatment with wilate® in patients with VWD have been hypersensitivity reactions.

Please see full prescribing information.

To report suspected adverse reactions, contact:
Octapharma USA Inc.
866-766-4860 or
FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch

References

  1.  Lethagen S, Carlson M, Hillarp A. A comparative in vitro evaluation of six von Willebrand factor concentrates. Haemophilia. 2004;10:243-249.
  2. Favaloro EJ, Bukuya M, Martinelli T, et al. A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates. Thromb Haemost. 2002;87:466-476.
  3. Stadler M, Gruber G, Kannicht C, et al. Characterisation of a novel high-purity, double virus inactivated von Willebrand factor and factor VIII concentrate (Wilate®). Biologicals. 2006;34:1-8.
  4. Kessler CM, Friedman K, Schwartz BA, Gill JC, Powell JS, for the wilate® PK Study Investigators. The pharmacokinetic diversity of two von Willebrand factor (VWF)/factor VIII (FVIII) concentrates in subjects with congenital von Willebrand disease. Results from a prospective, randomised crossover study. Thromb Haemost. 2011;106:279-288.
  5. Fuchs B, Schulz A, Budde U, et al. Flow–based measurements of von Willebrand factor (VWF) function: Binding to collagen and platelet adhesion under physiological shear rate. Thrombosis Research. 2010;125:239-245.

Photos are of models and for illustrative purposes only.

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