Identification and Functional Characterization of von Willebrand Disease

Identification and Functional Characterization of von Willebrand Disease

Favaloro Emmanuel J
US Hematology Volume 2
Published: January 2010
download article

| More
dots

Abstract
The identification and functional characterization of von Willebrand disease (VWD) is challenging due to clinical uncertainty and limitations in test processes and panels used by laboratories, and because the classification scheme does not always permit unequivocal assignment of subtype. This article reviews contemporary alternatives to classic diagnostic approaches, including the incorporation of extended core test panels inclusive of the collagen-binding assay, and the potential for desmopressin (DDAVP) challenges not only to provide therapeutic information but also to assist the better characterization of individuals with defects or deficiencies in von Willebrand factor (VWF). Supplementary assays such as the PFA-100® and the VWF propeptide assay following DDAVP challenge are also worth considering.

Keywords
Desmopressin (DDAVP), von Willebrand factor (VWF), von Willebrand disease (VWD), diagnosis, classification

Disclosure: The authors have no conflicts of interest to declare.
Received: May 15, 2009 Accepted: June 21, 2009
Correspondence: Emmanuel J Favaloro, PhD, Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia. E: emmanuel.favaloro@swahs.health.nsw.gov.au

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is characterized by low levels of and/or abnormal function in the plasma protein von Willebrand factor (VWF). Typically, laboratory investigation entails initial plasma testing of factor VIII coagulant (FVIII:C), VWF protein antigen (VWF:Ag), and VWF activity, which is classically assessed using the ristocetin co-factor (VWF:RCo) assay.1–5 Newer tests of VWF function include the collagen-binding assay (VWF:CB) and other putative activity (VWF:Act) assays.2–6 Depending on initial test patterns and local availability, supplementary laboratory testing may also employ VWF multimers, ristocetin-induced platelet agglutination (or aggregation) (RIPA), VWF–FVIII binding (VWF:FVIIIB), and, in some cases, genetic analysis.1–7

Six types of VWD can be defined: types 1, 2A, 2B, 2M, 2N, and 3.1 7 Type 1 VWD is a partial quantitative defect and is simply defined by a reduction in plasma VWF; thus, the presenting VWF is essentially qualitatively normal.’ Type 3 VWD is defined by (virtual) complete deficiency of VWF, and is diagnosed when there is essentially no measurable plasma VWF. Type 2 VWD defines qualitative defects of VWF. Type 2A VWD is defined by decreased VWF-dependent platelet adhesion and a selective deficiency of high-molecular-weight (HMW) VWF multimers, which can arise from either decreased production or increased plasma clearance. Type 2B VWD is defined by an increased affinity of VWF for its platelet receptor, glycoprotein Ib alpha (GPIbα). This increased affinity typically (but not always) results in clearance of both HMW VWF and platelets from circulation, and thus (usually mild) thrombocytopenia. Type 2N VWD is characterized by markedly decreased binding affinity of VWF for factor VIII, and presents phenotypically like hemophilia A. Type 2M VWD is defined by decreased VWF-dependent platelet adhesion without selective deficiency of HMW VWF multimers. In practice, type 2M VWD comprises a composite of different functional VWF defects and essentially any qualitative defect that cannot otherwise be characterized within other type 2 VWD groups. The most common type 2M VWD variants so far identified display defective binding of VWF to GPIbα, but essentially (near) normal collagen binding.

To read full article please click here.

Keywords:
Desmopressin (DDAVP), von Willebrand factor (VWF), von Willebrand disease (VWD), diagnosis, classification, von Willebrand Disease diagnosis, von Willebrand Disease vwd, von Willebrand bleeding disorder, von Willebrand Disease hemophilia, von Willebrand factor antigen, ddavp von Willebrand Disease disease,

References:
  1. Sadler JE, Budde U, Eikenboom JCJ, et al., J Thromb Haemost, 2006;4:2103–14.
  2. Favaloro EJ, Semin Thromb Hemost, 2006;32:456–71.
  3. Favaloro EJ, Semin Thromb Hemost, 2007;33:727–44.
  4. Favaloro EJ, Semin Thromb Hemost, 2009;35:60–75.
  5. Favaloro EJ. In: Preston E, Kitchen S, Olson JD (eds), Quality in Laboratory Hemostasis and Thrombosis, Oxford: Wiley-Blackwell, 2009;125–36.
  6. Favaloro EJ, Bonar R, Meiring M, et al., Thromb Haemost, 2007;98:346–58.
  7. James P, Lillicrap D, Semin Thromb Hemost, 2008;34:502–8.
  8. Favaloro EJ, Bonar R, Marsden K (on behalf of the RCPA QAP Haemostasis Committee), Clin Lab Sci, 2008;21: 178–85.
  9. Duncan EM, Bonar R, Rodgers SE, et al., Int J Lab Hematol, 2008 (Epub ahead of print).
  10. Favaloro EJ, Semin Thromb Hemost, 2008;34:113–27.
  11. Othman M, Favaloro EJ, Semin Thromb Hemost, 2008;34: 520–31.
  12. Favaloro EJ, Bonar R, Kershaw G, et al., RSemin Thromb Hemost, 2006;32:505–13.
  13. Goodeve A, Eikenboom J, Castaman G, et al., Blood, 2007;109:112–21.
  14. James PD, Paterson AD, Notley C, et al., J Thromb Haemost, 2006;4:783–92.
  15. James PD, Notley C, Hegadorn C, et al., Blood, 2007;109:145–54.
  16. Cumming A, Grundy P, Keeney S, et al., Thromb Haemost, 2006;96:630–41.
  17. Penas N, Pérez-Rodríguez A, Torea JH, et al., Am J Hematol, 2005;80:188–96.
  18. Riddell AF, Jenkins PV, Nitu-Whalley IC, et al., Br J Haematol, 2002;116: 187–92.
  19. 2007;5:1914–22.
  20. Meijer P, Haverkate F, Semin Thromb Hemost, 2006;32:485–91.
  21. Kitchen S, Jennings I, Woods TA, et al., Semin Thromb Hemost, 2006;32:492–8.
  22. Hayes TE, Brandt JT, Chandler WL, et al., Semin Thromb Hemost, 2006;32:499–504.
  23. Favaloro EJ, J Thromb Haemost, 2008;6:1999–2001.
  24. Adcock DM, Bethel M, Valcour A, Semin Thromb Hemost, 2006;32:472–9.
  25. Meiring M, Badenhorst PN, Kelderman M, Clin Chem Lab Med, 2007;45:1068–72.
  26. Favaloro EJ, Thom J, Patterson D, et al., Thromb Res, 2009;123:862–8.
  27. Favaloro EJ, Dean M, Grispo L, et al., Am J Hematol, 1994;45:205–11.
  28. Michiels JJ, van de Velde A, van Vliet HH, et al., Semin Thromb Hemost, 2002;28:111–32.
  29. Michiels JJ, Berneman Z, Gadisseur A, et al., Clin Appl Thromb Hemost, 2006;12: 277–95.
  30. Michiels JJ, van Vliet HH, Berneman Z, et al., Clin Appl Thromb Hemost, 2007;13:14–34.
  31. Nichols WL, Hultin MB, James AH, et al., Haemophilia, 2008;14: 171–232.
  32. Federici AB, Mazurier C, Berntorp E, et al., Blood, 2004;103:2032–8.
  33. Pasi KJ, Collins PW, Keeling DM, et al., Haemophilia, 2004;10:218–31.
  34. Federici AB, Castaman G, Mannucci PM, Haemophilia, 2002;8:607–21.
  35. Favaloro EJ, Kershaw G, Bukuya M, et al., Haemophilia, 2001;7: 180–89.
  36. Favaloro EJ, Semin Thromb Hemost, 2006;32:537–45.
  37. Favaloro EJ, Semin Thromb Hemost, 2006;6:566–76.
  38. Favaloro EJ, Semin Thromb Hemost, 2008;34:709–33.
  39. van Vliet HHDM, Kappers-Klunne MC, Leebeek FWG, et al.,
  40. Favaloro EJ, Thromb Haemost, 2008;100:371–3.
  41. Favaloro EJ, Thom J, Patterson D, et al., Blood Coag Fibrinolysis, 2009; in press.
  42. Borchiellini A, Fijnvandraat K, ten Cate JW, et al., Blood, 1996;88:2951–8.
  43. Sztukowska M, Gallinaro L, Cattini MG, et al., Br J Haematol, 2008;143: 107–14.
  44. Schooten CJ, Tjernberg P, Westein E, et al., J Thromb Haemost, 2005;3:2228–37.
  45. Haberichter SL, Balisteri M, Christopherson P, et al., Blood, 2006;108:3344–51.
  46. Casonato A, Pontara E, Sartorello F, et al., Blood, 2002;99:180–84.
  47. Haberichter SL, Castaman G, Budde U, et al., Blood, 2008;111:4979–85.
  48. Millar CM, Riddell AF, Brown SA, et al., Thromb Haemost, 2008; 99:916–24.
  49. Favaloro EJ, Thromb Haemost, 2009;102: in press.
  50. Favaloro EJ, J Thromb Haemost, 2009 May 12 (Epub ahead of print).
  51. Keeney S, Bowen D, Cumming A, et al., Haemophilia, 2008;14:1099–1111.
  52. Koutts J, Semin Thromb Hemost, 2006;32:445–55.

Copyright® 2004 - 2010 Business Briefings, Ltd. All rights reserved.
Touch Oncology is for informational purposes and should not be considered medical advice, diagnosis or treatement recommendations.