Laboratory Diagnosis and Management of von Willebrand Disease in Turkey: Izmir Experience

 

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ABSTRACT

von Willebrand disease (VWD) is caused by a deficiency or dysfunction of von Willebrand factor (VWF). The pathophysiology, classification, diagnosis, and management of VWD are relatively complex, but their understanding is important for proper diagnosis and management of patients with VWD. There are inherent difficulties in both the identification and classification of VWD because of clinical uncertainty and the limitations in the test processes and test panels typically used by laboratories. The most common test panel employed by laboratories, particularly in the geographic regions covered by the mutational studies, would comprise factor VIII coagulant (FVIII:C), VWF protein (antigen; VWF:Ag), and ristocetin cofactor (VWF:RCo). In our center, use of a desmopressin challenge with our core four-test panel (i.e., VWF:Ag, VWF:RCo, FVIII:C, and PFA-100) is expected to further assist laboratory diagnosis of VWD in Turkey. Molecular genetics is a rather new approach for Turkey, with gene analyses related to VWD being initiated in one center and the results used for confirmation of diagnosis in limited cases.

REFERENCES

• 1 Sadler JE, Budde U, Eikenboom JCJ Working Party on von Willebrand Disease Classification 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 (10) 2103-2114
  Google Scholar
• 2 Biron C, Mahieu B, Rochette A et al.. Preoperative screening for von Willebrand disease type 1: low yield and limited ability to predict bleeding.  J Lab Clin Med. 1999;  134 (6) 605-609
  Google Scholar
• 3 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease.  Blood. 1987;  69 (2) 454-459
  Google Scholar
• 4 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 (6) 893-898
  Google Scholar
• 5 Yilmaz D, Karapınar B, Yeniay BS, Balkan C, Bilenoğlu B, Kavaklı K. İzmir'de von Willebrand Hastalığı sıklığını belirtmeye yönelik epidemiyolojik çalışma.  [in Turkish] Ege Pediatri Bülteni.. 2005;  12 (3) 151-159
  Google Scholar
• 6 Gürsel T, Kavaklı K, Aktuğlu G. Hemofili ve von Willebrand Hastalığında Tanı ve Tedavi, Türk Hematoloji Derneği-Hemofili Alt Komitesi (Turkish Guideline). Istanbul, Turkey: Rehberi; 1999: 2-5
  Google Scholar
• 7 World Federation of Hemophilia .World Federation of Hemophilia Report on the Annual Global Survey 2008. Available at: http://www.wfh.org/2/docs/Publications/Statistics/2007-Survey-Report.pdf Accessed May 4, 2011
  Google Scholar
• 8 Favaloro EJ. Laboratory identification of von Willebrand disease: technical and scientific perspectives.  Semin Thromb Hemost. 2006;  32 (5) 456-471
  Google Scholar
• 9 Favaloro EJ. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult.  Semin Thromb Hemost. 2007;  33 (8) 727-744
  Google Scholar
• 10 Miller CH, Haff E, Platt SJ et al.. Measurement of von Willebrand factor activity: relative effects of ABO blood type and race.  J Thromb Haemost. 2003;  1 (10) 2191-2197
  Google Scholar
• 11 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 (2) 171-232
  Google Scholar
• 12 James P, Lillicrap D. The role of molecular genetics in diagnosing von Willebrand disease.  Semin Thromb Hemost. 2008;  34 (6) 502-508
  Google Scholar
• 13 Eikenboom J, Van Marion V, Putter H et al.. Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD.  J Thromb Haemost. 2006;  4 (4) 774-782
  Google Scholar
• 14 Budde U, Schneppenheim R, Eikenboom J et al.. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).  J Thromb Haemost. 2008;  6 (5) 762-771
  Google Scholar
• 15 Favaloro EJ, Bonar R, Kershaw G RCPA QAP in Haematology et al. Laboratory diagnosis of von Willebrand's disorder: quality and diagnostic improvements driven by peer review in a multilaboratory test process.  Haemophilia. 2004;  10 (3) 232-242
  Google Scholar
• 16 Favaloro EJ, Thom J, Baker R. Australasian Society for Thrombosis and Haemostasis (ASTH) Emerging Technologies Group . Assessment of current diagnostic practice and efficacy in testing for von Willebrand's disorder: results from the second Australasian multi-laboratory survey.  Blood Coagul Fibrinolysis. 2000;  11 (8) 729-737
  Google Scholar
• 17 Favaloro EJ, Bonar R, Meiring M, Street A, Marsden K. RCPA QAP in Haematology . 2B or not 2B? Disparate discrimination of functional VWF discordance using different assay panels or methodologies may lead to success or failure in the early identification of type 2B VWD.  Thromb Haemost. 2007;  98 (2) 346-358
  Google Scholar
• 18 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 (1) 35-39
  Google Scholar
• 19 Favaloro EJ. Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA-100 and von Willebrand factor:collagen binding activity as coupled strategies.  Semin Thromb Hemost. 2006;  32 (6) 566-576
  Google Scholar
• 20 Akin M, Karapinar DY, Balkan C, Ay Y, Kavakli K. An evaluation of the DDAVP infusion test with PFA-100 and vWF activity assays to distinguish vWD types in children.  Clin Appl Thromb Hemost. 2010;  May 11 (Epub ahead of print)
  Google Scholar
• 21 Michiels JJ, Berneman Z, Gadisseur A, van der Planken M, Schroyens W, van Vliet HHDM. Laboratory diagnosis and molecular basis of mild von Willebrand disease type 1.  Acta Haematol. 2009;  121 (2-3) 85-97
  Google Scholar
• 22 Favaloro EJ. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD): a rebuttal.  J Thromb Haemost. 2008;  6 (11) 1999-2001; author reply 2002–2003
  Google Scholar
• 23 Favaloro EJ, Kershaw G, Bukuya M, Hertzberg M, Koutts J. 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;  7 (2) 180-189
  Google Scholar
• 24 Favaloro EJ, Thom J, Patterson D et al.. Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?.  Thromb Res. 2009;  123 (6) 862-868
  Google Scholar
• 25 Mazurier C, Goudemand J, Hilbert L, Caron C, Fressinaud E, Meyer D. Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology.  Best Pract Res Clin Haematol. 2001;  14 (2) 337-347
  Google Scholar
• 26 Michiels JJ, van de Velde A, van Vliet HH, van der Planken M, Schroyens W, Berneman Z. 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 (2) 111-132
  Google Scholar

Mehmet AkinM.D. 

Pediatric Hematologist, Department of Pediatric Hematology

Ege University, Bornova, Izmir, Turkey

Email: drmehmetakin@yahoo.com.tr