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Thromb Haemost 2002; 87(02): 224-230
DOI: 10.1055/s-0037-1612977
Letters to the Editor
Schattauer GmbH

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

D. Lillicrap
1   Departments of Pathology and Medicine, Queen’s University, Kingston, Ontario
,
M.-C. Poon
2   Departments of Medicine, Pediatrics and Oncology, University of Calgary, and the Canadian Blood Services, Calgary, Alberta
,
I. Walker
3   Dept. of Medicine, McMaster University Medical Centre, Hamilton, ON
,
F. Xie
4   Aventis-Behring, Ottawa, ON, Canada
,
B.A. Schwartz
4   Aventis-Behring, Ottawa, ON, Canada
,
members of the Association of Hemophilia Clinic Directors of Canada › Author Affiliations
Further Information

Publication History

Received 29 May 2001

Accepted after resubmission 16 November 2001

Publication Date:
13 December 2017 (online)

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Summary

The present study was initiated to evaluate the safety and efficacy of Haemate-P® (Humate-P® in North America) (anti-hemophilic FVIII/VWF complex [human] dried, pasteurized) dosed in ristocetin cofactor units (VWF:RCo) in the treatment of von Willebrand disease (VWD) patients in Canada. This retrospective data collection reviewed the medical records of VWD patients treated under the Canadian Emergency Drug Release Program from November 22, 1991, to April 30, 1996. Data collection was accomplished by on-site retrieval from source data for 97 patients. Dosing was based on the German package insert, which lists only Factor VIII:C (FVIII:C) units, which were converted in the study analysis to VWF:RCo units based on the analysis of the individual manufactured lots of product used in these patients (average ratio of 2.6 IU VWF:RCo per IU FVIII:C). Twenty five different lots of Haemate-P/Humate-P were used to treat 437 different events in the 97 study patients (344 hemorrhagic events, 73 surgical interventions and 20 prophylactic infusion cycles). Overall, the median dose of concentrate per infusion used to treat surgical events was 69.1 IU VWF:RCo/kg (range 11.9-222.8); bleeding events 55.3 IU VWF:RCo/kg (range 17.1-227.5) and prophylaxis 41.6 IU VWF:RCo/kg (range 34.6-81.0). Treatment periods varied, with the majority of events treated for ≤ 10 days (91%). Fifty percent of events that were treated longer than 10 days were given for prophylactic reasons. Efficacy was determined in a standardized manner by the physician, based on dosing in VWF:RCo activity. An overall clinical result of “excellent” or “good” was reported in 97% (424/437) of treatment events. A pediatric sub-population analysis of the patient population reported “excellent/good” efficacy in 100% (17/17) of treatment events in infants, 95% (155/164) in children, and 94% (76/81) in adolescent patients. Related adverse events (AEs) were observed in only 4 (4%) patients and were not deemed to be serious. The findings in this study confirm the safety and efficacy of Haemate-P/Humate-P using VWF:RCo dosing in pediatric and adult patients with various types of VWD.

Keywords

von Willebrand disease - Haemate-P/Humate-P - ristocetin cofactor units
 

  • References

  • 1 Miller CH, Lenzi R, Breen C. Prevalence of von Willebrand’s disease among U.S adults. Blood 1987; 70: 377a.
    PubMedGoogle Scholar
  • 2 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987; 69: 454-9.
    PubMedGoogle Scholar
  • 3 Werner EJ, Broxson EH, Tucker EL, Giroux DS, Shults J, Abshire TC. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr 1993; 123: 893-8.
    CrossrefPubMedGoogle Scholar
  • 4 Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-55.
    PubMedGoogle Scholar
  • 5 Ingerslev J, Gürsel T. Diagnosis of von Willebrand disease. Haemophilia 1999; 05 (02) 50-6.
    CrossrefPubMedGoogle Scholar
  • 6 Bloom AL. von Willebrand factor: c linical features of inherited and acquired disorders. Mayo Clin Proc 1991; 66: 743-51.
    CrossrefPubMedGoogle Scholar
  • 7 Menache D, Aronson DL. New treatments of von Willebrand disease: plasma derived von Willebrand factor concentrates. Thromb Haemost 1997; 78: 566-70.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Berntorp E, Nilsson IM. Use of a high-purity factor VIII concentrate (Hemate P) in von Willebrand’s disease. Vox Sang 1989; 56: 212-7.
    PubMedGoogle Scholar
  • 9 Fricke WA, Yu MY. Characterization of von Willebrand factor in factor VIII concentrates. Am J Hematol 1989; 31: 41-5.
    CrossrefPubMedGoogle Scholar
  • 10 Mannucci PM, Tenconi PM, Castaman G, Rodeghiero F. Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial. Blood 1992; 79: 3130-7.
    PubMedGoogle Scholar
  • 11 Rodeghiero F, Castaman G, Meyer D, Mannucci PM. Replacement therapy with virus-inactivated plasma concentrates in von Willebrand disease. Vox Sang 1992; 62: 193-9.
    PubMedGoogle Scholar
  • 12 Schimpf K, Mannucci PM, Kreutz W, Brackmann HH, Auerswald G, Ciavarella N, Mosseler J, DeRosa V, Kraus B, Brueckmann C. et al. Absence of hepatitis after treatment with a pasteurized factor VIII concentrate in patients with hemophilia and no previous transfusions. N Engl J Med 1987; 316: 918-22.
    CrossrefPubMedGoogle Scholar
  • 13 Kohler M, Hellstern P, Wenzel E. The use of heat-treated Factor VIIIconcentrates in von Willebrand’s disease. Blut 1985; 50: 25-7.
    CrossrefPubMedGoogle Scholar
  • 14 Kreuz W, Mentzer D, Becker S, Scharrer I, Kornhuber B. Haemate P in children with von Willebrand’s disease. Haemostasis 1994; 24: 304-10.
    PubMedGoogle Scholar
  • 15 Chang AC, Rick ME, Pierce LR, Weinstein MJ. Summary of a workshop on potency and dosage of von Willebrand factor concentrates. Haemophilia 1998; 04 (Suppl. 03) 1-6 1-1-9980..
    CrossrefPubMedGoogle Scholar
  • 16 Siekmann J, Turecek PL, Schwarz HP. The determination of von Willebrand factor activity by collagen binding assay. Haemophilia 1998; 04 (Suppl. 03) 15-24.
    CrossrefPubMedGoogle Scholar
  • 17 Bennett E, Dormandy K. Pool’s cryoprecipitate and exhausted plasma in the treatment of von Willebrand’s disease and factor-XI deficiency. Lancet 1966; 02: 731-2.
    PubMedGoogle Scholar
  • 18 Goudemand J, Negrier C, Ounnoughene N, Sultan Y. Clinical management of patients with von Willebrand’s disease with a VHP vWF concentrate: the French experience. Haemophilia 1998; 04 (Suppl. 03) 48-52.
    CrossrefPubMedGoogle Scholar
  • 19 Mazurier C. In vitro evaluation of the haemostatic value of the LFB-von Willebrand factor concentrate. Haemophilia 1998; 04 (Suppl. 03) 40-3.
    CrossrefPubMedGoogle Scholar
  • 20 van Genderen PJ, Michiels JJ. Acquired von Willebrand disease. Baillieres Clin Haematol 1998; 11: 319-30.
    CrossrefPubMedGoogle Scholar
  • 21 Tefferi A, Nichols WL. Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis, and treatment. Am J Med 1997; 103: 536-40.
    CrossrefPubMedGoogle Scholar
  • 22 Federici AB. Therapeutic approaches to acquired von Willebrand syndrome. Expert Opin Investig Drugs 2000; 09: 347-54.
    CrossrefPubMedGoogle Scholar
  • 23 Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
    CrossrefPubMedGoogle Scholar
  • 24 O’Donnell J, Tuddenham EG, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-73.
    CrossrefPubMedGoogle Scholar
  • 26 Federici AB, Mannucci PM. Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease. Haemophilia 1998; 04 (Suppl. 03) 7-10.
    CrossrefPubMedGoogle Scholar
  • 27 Fressinaud E, Veyradier A, Sigaud M, Boyer-Neumann C, Le Boterff C, Meyer D. Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates. Br J Haematol 1999; 106: 777-83.
    CrossrefPubMedGoogle Scholar
  • 28 Favaloro EJ. Detection of von Willebrand disorder and identification of qualitative von Willebrand factor defects. Direct comparison of commercial ELISA-based von Willebrand factor activity options. Am J Clin Pathol 2000; 114: 608-18.
    CrossrefPubMedGoogle Scholar
  • 29 Metzner HJ, Hermentin P, Cuesta-Linker T, Langner S, Müller GH, Friedebold J. Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis. Haemophilia 1998; 04 (Suppl. 03) 25-32.
    CrossrefPubMedGoogle Scholar