Download PDF
Thromb Haemost 2011; 105(06): 1072-1079
DOI: 10.1160/TH10-10-0631
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Efficacy and safety of a new generation von Willebrand factor/factor VIII concentrate (Wilate®) in the management of perioperative haemostasis in von Willebrand disease patients undergoing surgery

Jerzy Windyga
1   Institute of Haematology and Transfusion Medicine, Warsaw, Poland
,
Mario von Depka-Prondzinski
2   Werlhof Institute, Hannover, Germany
,
the European Wilate® Study Group › Author Affiliations
Further Information

Publication History

Received: 03 October 2010

Accepted after major revision: 11 February 2011

Publication Date:
28 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

The aim of this study was to assess the efficacy of Wilate®, a new generation, plasma-derived, high-purity, double virus-inactivated von Willebrand factor (VWF) and factor VIII (FVIII) concentrate (ratio close to physiological 1:1) in the perioperative management of haemostasis in von Willebrand disease (VWD). Data for VWD patients who received Wilate® for perioperative management were obtained from four European, prospective, open-label, non-controlled, non-randomised, multicentre phase II or III clinical trials. A total of 57 surgical procedures were performed (major: n = 27; minor n = 30) in 32 patients. The majority of patients (n = 19, 59.4%) had type 3 VWD, 9 (28.1%) had type 2 VWD and four (12.5%) had type 1 VWD. During major surgery, median daily FVIII dose and mean number of infusions were 25 IU•kg-1 FVIII (VWF:RCô23 IU•kg-1) and 11.0, respectively. Corresponding values for minor surgery were 35 IU•kg-1 (VWF:RCo ~32 IU•kg-1) and 1.5. The efficacy of Wilate® was rated by the investigator as excellent or good in 51 of 53 (96%) procedures. Tolerability was rated as very good or good in 100% of major surgeries (27 of 27) and minor surgeries (29 of 29). Wilate® is an effective and well-tolerated VWF/FVIII replacement therapy in the perioperative management of haemostasis in patients with VWD. It can be administered at a similar FVIII dose, but at a lower VWF dose, as compared to older generation products. Clinical benefits were shown in a population with a high proportion of type 3 VWD patients.

Keywords

Factor VIII - surgery - von Willebrand disease - von Willebrand factor - Wilate®

* See Appendix for a list of participating Study members.


 

  • References

  • 1 Castaman G, Federici AB, Rodeghiero F. et al. Von Willebrand‘s disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment. Haematologica 2003; 88: 94-108.
    PubMedSearch in Google Scholar
  • 2 Sadler JE, Budde U, Eikenboom JC. et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von willebrand Factor. J Thromb Haemost 2006; 4: 2103-2114.
    CrossrefPubMedSearch in Google Scholar
  • 3 Schneppenheim R. The evolving classification of von Willebrand disease. Blood Coagul Fibrinolysis 2005; 16 (Suppl. 01) S3-S10.
    CrossrefPubMedSearch in Google Scholar
  • 4 Federici AB. Management of von Willebrand disease with factor VIII/von willebrand factor concentrates: results from current studies and surveys. Blood Coagul Fibrinolysis 2005; 16 (Suppl. 01) S17-S21.
    CrossrefPubMedSearch in Google Scholar
  • 5 Nichols WL, Hultin MB, James AH. et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14: 171-232.
    CrossrefPubMedSearch in Google Scholar
  • 6 Berntorp E. Prophylaxis and treatment of bleeding complications in von willebrand disease type 3. Semin Thromb Hemost 2006; 32: 621-625.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Lethagen S. Clinical experience of prophylactic treatment in von Willebrand disease. Thromb Res 2006; 118 (Suppl. 01) S9-S11.
    CrossrefPubMedSearch in Google Scholar
  • 8 Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-1455.
    PubMedSearch in Google Scholar
  • 9 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: 281-288.
    CrossrefPubMedSearch in Google Scholar
  • 10 Berntorp E, Windyga J. Treatment and prevention of acute bleedings in von willebrand disease ﺹ efficacy and safety of Wilate, a new generation von Willebrand factor/factor VIII concentrate. Haemophilia 2009; 15: 122-130.
    CrossrefPubMedSearch in Google Scholar
  • 11 Lillicrap D, Poon MC, Walker I. et al. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, Haemate P/Humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost 2002; 87: 224-230.
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Mannucci PM. Treatment of von Willebrand‘s disease. N Engl J Med 2004; 351: 683-694.
    CrossrefPubMedSearch in Google Scholar
  • 13 Thompson AR, Gill JC, Ewenstein BM. et al. Successful treatment for patients with von Willebrand disease undergoing urgent surgery using factor VIII/VWF concentrate (Humate-P). Haemophilia 2004; 10: 42-51.
    CrossrefPubMedSearch in Google Scholar
  • 14 Lethagen S, Kyrle PA, Castaman G. et al. von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery. J Thromb Haemost 2007; 5: 1420-1430.
    CrossrefPubMedSearch in Google Scholar
  • 15 Rivard GE, Aledort L. Efficacy of factor VIII/von Willebrand factor concentrate Alphanate in preventing excessive bleeding during surgery in subjects with von Willebrand disease. Haemophilia 2008; 14: 271-275.
    CrossrefPubMedSearch in Google Scholar
  • 16 Hernandez-Navarro F, Quintana M, Jimenez-Yuste V. et al. Clinical efficacy in bleeding and surgery in von Willebrand patients treated with Fanhdi a highly purified, doubly inactivated FVIII/VWF concentrate. Haemophilia 2008; 14: 963-967.
    CrossrefPubMedSearch in Google Scholar
  • 17 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-155.
    CrossrefPubMedSearch in Google Scholar
  • 18 Kraaijenhagen RA, Anker PS, Koopman MM. et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-462.
    CrossrefPubMedSearch in Google Scholar
  • 20 Bank I, Libourel EJ, Middeldorp S. et al. Elevated levels of FVIII: C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 2005; 3: 79-84.
    CrossrefPubMedSearch in Google Scholar
  • 21 Mannucci PM, Chediak J, Hanna W. et al. Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study. Blood 2002; 99: 450-456.
    CrossrefPubMedSearch in Google Scholar
  • 22 Pock K, Stadler M, Gruber G. et al. Product features of novel generation VWF/ FVIII concentrate in a comparison with first generation products. J Thromb Haemost. 2007 5: Abstract P-W-183.
    PubMedSearch in Google Scholar