Download PDF
Thromb Haemost 2008; 100(03): 462-468
DOI: 10.1160/TH07-08-0527
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

PFA-100 monitoring of von Willebrand factor (VWF) responses to desmopressin (DDAVP) and factor VIII/VWF concentrate substitution in von Willebrand disease type 1 and 2

Huub H. D. M. van Vliet
1   Department of Haematology, Erasmus MC, Rotterdam, The Netherlands
,
Mies C. Kappers-Klunne
1   Department of Haematology, Erasmus MC, Rotterdam, The Netherlands
,
Frank W. G. Leebeek
1   Department of Haematology, Erasmus MC, Rotterdam, The Netherlands
,
Jan J. Michiels
2   Department of Haematology, Antwerp University Hospital, University of Antwerp, Belgium
› Author Affiliations
Further Information

Publication History

Received 29 August 2007

Accepted after minor revision 25 June 2008

Publication Date:
22 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Dose-response relationship was studied between PFA-100 closure times (PFA CTs) and factor (F)VIII-von Willebrand factor (VWF) parameters in patients with von Willebrand disease (VWD) type 1 and type 2 before and after treatment with DDAVP (n=84) or FVIII/VWF concentrate (n=38). DDAVP treatment of patients with VWD type 1 normalised the PFA CTs by increasing VWF levels to normal. Of the 14 patients with VWD type 2, PFA CTs did not normalize in eight. Haemate-P substitution in patients with VWD type 1 induced a less favourable response as compared to DDAVP, because PFA CTs did not correct in all patients. Of 12 patients with VWD type 2 treated with Haemate-P, six showed a correction of PFA CTs (<250 sec), which correlated with the normalisation of the VWF CB/ Ag ratio. In-vitro studies were performed by using whole blood of patients with VWD and adding various amounts of FVIII/VWF concentrate. Addition of Haemate-P induced an increase of the VWF CB/Ag ratio from 0.30 to 0.70 in blood of patients with VWD type 2 with correction of the PFA CTs. Immunate did not result in an increase of VWF CB/Ag ratio in blood of VWD type 2 patients, and the PFA CTs remained prolonged. We conclude that PFA-100 might be an adequate instrument not only for diagnosis but also for monitoring of DDAVP responses and FVIII/ VWF substitution of patients with VWD type 1 and 2,but this is dependent upon the type of VWD and the concentrate used.

Keywords

von Willebrand disease - DDAVP - Haemate-P - PFA-100 - vonWille-brand factor collagen binding
 

  • References

  • 1 Mannucci PM. Treatment of von Willebrand’s Disease. N Engl J Med 2004; 351: 683-694.
    CrossrefPubMedSearch in Google Scholar
  • 2 Sadler JE, Budde U, Eikenboom JCJ. et al. The working party on von Willebrand disease classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand. J Thromb Haemost 2006; 04: 2103-2114.
    CrossrefPubMedSearch in Google Scholar
  • 3 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
  • 4 Federici AB, Castaman G, Thompson A. et al. Von Willebrand’ s disease: clinical management. Haemophilia 2006; 12 (Suppl. 03) 152-158.
    CrossrefPubMedSearch in Google Scholar
  • 5 Chang AC, Rick ME, Ross Pierce L. et al. Summary of a workshop on potency and dosage of von Willebrand factor concentrates. Haemophilia 1998; 04: 1-6.
    CrossrefPubMedSearch in Google Scholar
  • 6 Cox Gill J, Ewenstein BM, Thompson AR. et al. for the Humate -P study group. Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P®): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy. Haemophilia 2003; 09: 688-695.
    CrossrefPubMedSearch in Google Scholar
  • 7 Fressinaud E, Veyradier A, Sigaud M. et al. Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates. Br J Haematol 1999; 106: 777-783.
    CrossrefPubMedSearch in Google Scholar
  • 8 Cattaneo M, Lecchi A, Agati B. et al. Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion. Thromb Res 1999; 96: 213-217.
    CrossrefPubMedSearch in Google Scholar
  • 9 Favaloro EJ, Kershaw G, Bukuya M. et al. Laboratory diagnosis of von Willebrand disorder (vWD) and monitoring of DDAVP therapy: efficacy of the PFA-100® and vWF:CBA as combined diagnostic strategies. Haemophilia 2001; 07: 180-189.
    CrossrefPubMedSearch in Google Scholar
  • 10 Franchini M, Gandini G, Manzato F. et al. Evaluation of the PFA-100 system for monitoring desmopressin therapy in patients with type 1 von Willebrand’s disease. Haematologica 2002; 87: 670.
    PubMedSearch in Google Scholar
  • 11 Cattaneo M, Federici AB, Lecchi A. et al. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost 1999; 82: 35-39.
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Meskal A, Vertessen F, Van der Planken M. et al. The Platelet Function Analyzer (PFA-100) may not be suitable for monitoring the therapeutic efficiency of von Willebrand concentrate in type III von Willebrand disease. Ann Hematol 1999; 78: 426-430.
    CrossrefPubMedSearch in Google Scholar
  • 13 Cejka J. Enzyme immunoassay for FVIII-related antigen. Clinical Chemistry 1984; 28: 1356-1358.
    PubMedSearch in Google Scholar
  • 14 Brown JE, Bosak JO. An ELISA test for the binding of von Willebrand factor antigen to collagen. Thromb Res 1986; 43: 303-311.
    CrossrefPubMedSearch in Google Scholar
  • 15 Van Genderen PJ, Budde U, Michiels JJ. et al. The reduction of large von Willebrand factor multimers in plasma in essential thrombocythemia is related to the platelet count. Br J Haematol 1996; 93: 962-965.
    CrossrefPubMedSearch in Google Scholar
  • 16 Favaloro EJ. Von Willebrand factor collagen-binding (activity) assay in the diagnosis of von Willebrand disease: A 15-year journey. Semin Thromb Hemost 2002; 28: 191-202.
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 MacFarlane DF, Stibbe J, Kirby EP. A method for assaying von Willebrand factor (ristocetine cofactor). Thromb Diath Haemorrh 1975; 34: 306-308.
    PubMedSearch in Google Scholar
  • 18 Ver Elst KMM, van Vliet HDM, Kappers-Klunne MC. et al. In vitro studies, pharmacokinetic studies and clinical use of high purity double virus inactivated FVIII/vWF concentrate (Immunate) in the treatment of von Willebrand disease. Thromb Haemost 2003; 92: 67-74.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Favaloro EJ. Laboratory monitoring of therapy in von Willebrand disease: Efficacy of the PFA-100 and the von Willebrand factor: collagen-binding activity as coupled strategies. Semin Thromb Hemost 2006; 32: 566-576.
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Michiels JJ, Berneman ZN, Van Der Planken M. et al. Bleeding prophylaxis for major surgery in patients with type 2 von Willebrand Disease with an intermediate purity factor VIII-von Willebrand factor concentrate (Haemate-P). Blood Coag Fibrinol 2004; 15: 323-330.
    CrossrefPubMedSearch in Google Scholar
  • 21 Michiels JJ, Van De Velde A, Van Vliet HHDM. et al. Response of von Willebrand factor parameters to desmopressin in patients with type 1 and type 2 congenital von Willebrand disease: diagnostic and therapeutic implications. Semin Thromb Hemost 2002; 28: 111-131.
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Budde U, Metzner HJ, Müller H-G. Comparative analysis and classification of von Willebrand factor/ factor VIII concentrates: Impact on treatment of patients with von Willebrand disease. Semin Thromb Hemost 2006; 32: 626-635.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Lillicrap D, Poon MC, Wlker I. et al. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, Haemate-P/Humate-P: Ristocetin Coafctor unit dosing in patients with von Willebrand disease. Thromb Haemost 2002; 87: 224-230.
    Thieme ConnectPubMedSearch in Google Scholar