Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease

Jan Jacques Michiels; Petr Smejkal; Katarzina Mayger; Gary Moore; Jan Blatny; Miroslav Penka; Ulrich Budde; Zwi Berneman; Inge Vangenechten; Alain Gadisseur

doi:doi:10.11648/j.ijcems.20190505.14

Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease

Jan Jacques Michiels, Petr Smejkal, Katarzina Mayger, Gary Moore, Jan Blatny, Miroslav Penka, Ulrich Budde, Zwi Berneman, Inge Vangenechten, Alain Gadisseur

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 5, Issue 5)

Received: 9 July 2019 Accepted: 30 August 2019 Published: 23 October 2019

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Abstract

A complete set of rapid activity and classical von Willebrand factor (VWF) assays for Willebrand disease (VWD) diagnosis was used in the present study to characterize VWD type 1, 2A, 2B and 2M patients due to mutations in the A1, A2 and A3 domains. The VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag ratios at cuttt off value of 0.7 separated VWD type 1 and LowVWF from VWD type 2. The results from the Brno cohort of VWD 2A patients with the G1579R mutation in the A2 domain in sixteen affected member from five families and in one case with the G1609R in the A2 domain revealed that the VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF: Ag ratios are marked decreased (range 0.03-0.27) to a similar degree as compared to VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios (range 0.03-0.27) due to the proteolytic loss of large and intermediate VWF multimers. The results in VWD 2B patients due to gain of ristocetin induced platelet agglutination (RIPA) function mutations R1306W, R1308C and R1341 in the A1 domain demonstrated that the ratios for VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag as compared to VWF:RCo/VWF:Ag ratio were markedly decreased in VWD 2B, whereas the VWF:GPIbM/VWF:Ag ratio was somewhat higher (range 0.32 to 0.36) in VWD 2M. VWD 2M patients due to loss of RIPA function mutation R1359K in the A1 domain are featured by decreased VWF ratios for WVF:RCo/Ag and VWF:GPIbR/Ag, but less decreased for the VWF:GPIbM/Ag ratio and normal VWF ratio for VWF:CB/Ag ratio the need to retain the VWF:CB assay to make a correct diagnosis of VWD 2M for its differentiation from VWD type 1. The G1415D mutation in the A1 domain is featured by decreased RIPA and decreased VWF:RCo/VWF:Ag ratio (VWD 2M) but normal values for VWF:CB/VWF:Ag, VWF:GPIbM/VWF:Ag and VWFGPIbR/VWF:Ag ratios consistent with VWD 2M. Double heterozygous P1266L/V1278I mutation in two patients and heterozygous E1292D/WT mutation in three patients in the A1 domain were diagnosed as VWD 2M or 1M associated with a secretion defect (SD). The Platelet Function Analyzer Closure Times (PFA-CT) are strongly prolonged in VWD 2A, 2B and 2M. and moderately prolonged between the upper limit of normal to 300 seconds in heterozygous mutated VWD type 1 patients.

Published in	International Journal of Clinical and Experimental Medical Sciences (Volume 5, Issue 5)
DOI	10.11648/j.ijcems.20190505.14
Page(s)	80-91
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Von Willebrand Disease, Von Willebrand Factor, VWF Acitivity, VWF Propeptide, Ristocetine Induced Platelet Agglutination RIPA, VWF Domain, Platelet Function Analyser, VWD Classification

References

[1]	Michiels JJ, Berneman Z, Gadisseur A, van der Planken M, Schroyens W, van de Velde A, van Vliet HHDM. Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2 E, 2M, 2N and 2U (Unclassifiable) von Willebrand disease. Clin Applied Thromb Hemostas 2006; 12 (4): 397-420.
[2]	Michiels JJ, van Vliet HHDM, Berneman Z, Gadisseur A, van der Planken M, Schroyens W, van de Velde A, Budde U. Intravenous DDAVP and FVIII-von Willebrand factor concentrate for the treatment and prophylaxis of bleedings in patients with von Willebrand disease type 1, 2 and 3. Clin Applied Thromb Hemostas 2007; 13 (1): 14-34.
[3]	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: 85-97.
[4]	Gadisseur A, Berneman Z, Schroyens W, Michiels JJ. Pseudohemophilia of Erik von Willebrand caused by homozygous one nucleotide deletion in exon 18 of the VW-factor gene World J Hematol 2013; 6; 2 (4): 99-108.
[5]	Gadisseur A, Hermans C, Berneman Z, Schroyens W, Declmyn H, Michiels JJ. Laboratory diagnosis and molecular classification of von Willebrand disease. Acta Haematol 2009; 121: 71-84.
[6]	Michiels JJ, Batorova A, Pricangova T, Smejkal P, Penka M, Vangenechten I, Gadisseur A. Changing insights in the diagnosis and classification of recessive and dominant von Willebrand diseases. World J Hematol 2016; 5 (3): 61-74. Doi: 10.5315/wjh.v5i.3.61.
[7]	Michiels JJ, Smejkal P, Penka M, Batorova A, Pricangova T, Budde U, Vangenechten I, Gadisseur A. Diagnostic differentiation of von Willebrand disease type 1 and 2 by von Willebrand factor multimer analysis and DDAVP challenge test Clin Applied Thromb Hemostas 2017; 23 (6): 518-531.
[8]	Vangenechten I, Mayger K, Smejkal P, Zapletal O, Michiels JJ, Moore GW, Gadisseur A. A comparative analysis of different automated von Willebrand factor glycoprotein Ib-binding activity assays in well typed von Willebrand disease patients. J Thromb Haemostas 2018; 16: 1-10 https://doi.org/10.1111/jth.14145.
[9]	Vangenechten I, Smejkal P, Zapletal O, Michiels JJ, Berneman Z, ZavrelovaJ, Blatny J, Penka M, Gadisseur A. Analysis of von Willebrand Disease in the South Moravian population (Czech Republic): Results from the BRNO-VWD Study. Thromb Haemostas 2019; 119: 594-605.
[10]	Patzke J, Budde U, Huber A, Mendez A, Muth H, Obser T, Peerschke E, Wilkins M, Schneppenheim R. Performance evaluation and multicentre study of a von Willebrand factor activity assay based on GLIb binding in the absence of ristocetin. Blood Coag Fibrinolys 2014; 25: 860-870.
[11]	Michiels JJ, Smejkal P, Zapletal O, Penka M, Blatny J, Budde U, Mayger K, Moore GW, Vangenechten I, Gadisseur A. Determination of two rapid von Willebrand factor (VWF) activity assays VWF: GPIbM and VWF: GPIbR in well-defined von Willebrand disease patients using a complete set of classical and sensitive VWF assays J Hemtol Thromb Dis 2019, 6: 5 DOI 10.417/2329-8790.100029.
[12]	Van den Heuvel E, de Laat B, Eckman CM, Michiels JJ, van Mourik J, Versteegh FGA. A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression. J Pediatr Hematol Oncol 2009; 31 (4): 277-280.
[13]	Michiels JJ, Smejkal P, Mayger K, Moore G, Budde U, Berneman Z, Vangenechten I, Gadisseur A, Blatny J, Penka M. Combined use of rapid von Willebrand factor (VWF) activity, VWF-propetide and classical VWF assays for improved diagnosis of von Willebrand disease type 1, 2N and 2E due to mutations in the D1, D2, D’, D3 and D4 domains of the VWF gene. Thromb Hemostas Res 2019; 3 (2) 1027.
[14]	Schneppenheim R, Michiels JJ, Obser T et al. A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease type 2A/2 E. Blood 2010; 115 (23): 4894-4901.
[15]	Van Duren C, Schoormans S, Brons P, Laros-Gorkom BAP, van Heerde WL. Determination of the VWF activity with the ristocetin independent gain of function Glycoprotein 1b Innovance von Willebrand Activity Assay. Poster-BARI International Conference WWW.bic2014org/posters.
[16]	Maitre E, Volot F, Mourey G, Aho LS, Ternisien C, Briquel ME, Bertrand MA, Tardy B, Frotscher B, Nguyen P, Dumont L, Vandroux D, Hezard N, Trossart M. Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStarand Innovance. Thromb Haemostas 2014; 112 DOI.org/10.1160/TH14-02-0108.

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Jan Jacques Michiels, Petr Smejkal, Katarzina Mayger, Gary Moore, Jan Blatny, et al. (2019). Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. International Journal of Clinical and Experimental Medical Sciences, 5(5), 80-91. https://doi.org/10.11648/j.ijcems.20190505.14

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ACS Style

Jan Jacques Michiels; Petr Smejkal; Katarzina Mayger; Gary Moore; Jan Blatny, et al. Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. Int. J. Clin. Exp. Med. Sci. 2019, 5(5), 80-91. doi: 10.11648/j.ijcems.20190505.14

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AMA Style

Jan Jacques Michiels, Petr Smejkal, Katarzina Mayger, Gary Moore, Jan Blatny, et al. Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. Int J Clin Exp Med Sci. 2019;5(5):80-91. doi: 10.11648/j.ijcems.20190505.14

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@article{10.11648/j.ijcems.20190505.14,
  author = {Jan Jacques Michiels and Petr Smejkal and Katarzina Mayger and Gary Moore and Jan Blatny and Miroslav Penka and Ulrich Budde and Zwi Berneman and Inge Vangenechten and Alain Gadisseur},
  title = {Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease},
  journal = {International Journal of Clinical and Experimental Medical Sciences},
  volume = {5},
  number = {5},
  pages = {80-91},
  doi = {10.11648/j.ijcems.20190505.14},
  url = {https://doi.org/10.11648/j.ijcems.20190505.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20190505.14},
  abstract = {A complete set of rapid activity and classical von Willebrand factor (VWF) assays for Willebrand disease (VWD) diagnosis was used in the present study to characterize VWD type 1, 2A, 2B and 2M patients due to mutations in the A1, A2 and A3 domains. The VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag ratios at cuttt off value of 0.7 separated VWD type 1 and LowVWF from VWD type 2. The results from the Brno cohort of VWD 2A patients with the G1579R mutation in the A2 domain in sixteen affected member from five families and in one case with the G1609R in the A2 domain revealed that the VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF: Ag ratios are marked decreased (range 0.03-0.27) to a similar degree as compared to VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios (range 0.03-0.27) due to the proteolytic loss of large and intermediate VWF multimers. The results in VWD 2B patients due to gain of ristocetin induced platelet agglutination (RIPA) function mutations R1306W, R1308C and R1341 in the A1 domain demonstrated that the ratios for VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag as compared to VWF:RCo/VWF:Ag ratio were markedly decreased in VWD 2B, whereas the VWF:GPIbM/VWF:Ag ratio was somewhat higher (range 0.32 to 0.36) in VWD 2M. VWD 2M patients due to loss of RIPA function mutation R1359K in the A1 domain are featured by decreased VWF ratios for WVF:RCo/Ag and VWF:GPIbR/Ag, but less decreased for the VWF:GPIbM/Ag ratio and normal VWF ratio for VWF:CB/Ag ratio the need to retain the VWF:CB assay to make a correct diagnosis of VWD 2M for its differentiation from VWD type 1. The G1415D mutation in the A1 domain is featured by decreased RIPA and decreased VWF:RCo/VWF:Ag ratio (VWD 2M) but normal values for VWF:CB/VWF:Ag, VWF:GPIbM/VWF:Ag and VWFGPIbR/VWF:Ag ratios consistent with VWD 2M. Double heterozygous P1266L/V1278I mutation in two patients and heterozygous E1292D/WT mutation in three patients in the A1 domain were diagnosed as VWD 2M or 1M associated with a secretion defect (SD). The Platelet Function Analyzer Closure Times (PFA-CT) are strongly prolonged in VWD 2A, 2B and 2M. and moderately prolonged between the upper limit of normal to 300 seconds in heterozygous mutated VWD type 1 patients.},
 year = {2019}
}

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TY  - JOUR
T1  - Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease
AU  - Jan Jacques Michiels
AU  - Petr Smejkal
AU  - Katarzina Mayger
AU  - Gary Moore
AU  - Jan Blatny
AU  - Miroslav Penka
AU  - Ulrich Budde
AU  - Zwi Berneman
AU  - Inge Vangenechten
AU  - Alain Gadisseur
Y1  - 2019/10/23
PY  - 2019
N1  - https://doi.org/10.11648/j.ijcems.20190505.14
DO  - 10.11648/j.ijcems.20190505.14
T2  - International Journal of Clinical and Experimental Medical Sciences
JF  - International Journal of Clinical and Experimental Medical Sciences
JO  - International Journal of Clinical and Experimental Medical Sciences
SP  - 80
EP  - 91
PB  - Science Publishing Group
SN  - 2469-8032
UR  - https://doi.org/10.11648/j.ijcems.20190505.14
AB  - A complete set of rapid activity and classical von Willebrand factor (VWF) assays for Willebrand disease (VWD) diagnosis was used in the present study to characterize VWD type 1, 2A, 2B and 2M patients due to mutations in the A1, A2 and A3 domains. The VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag ratios at cuttt off value of 0.7 separated VWD type 1 and LowVWF from VWD type 2. The results from the Brno cohort of VWD 2A patients with the G1579R mutation in the A2 domain in sixteen affected member from five families and in one case with the G1609R in the A2 domain revealed that the VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF: Ag ratios are marked decreased (range 0.03-0.27) to a similar degree as compared to VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios (range 0.03-0.27) due to the proteolytic loss of large and intermediate VWF multimers. The results in VWD 2B patients due to gain of ristocetin induced platelet agglutination (RIPA) function mutations R1306W, R1308C and R1341 in the A1 domain demonstrated that the ratios for VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag as compared to VWF:RCo/VWF:Ag ratio were markedly decreased in VWD 2B, whereas the VWF:GPIbM/VWF:Ag ratio was somewhat higher (range 0.32 to 0.36) in VWD 2M. VWD 2M patients due to loss of RIPA function mutation R1359K in the A1 domain are featured by decreased VWF ratios for WVF:RCo/Ag and VWF:GPIbR/Ag, but less decreased for the VWF:GPIbM/Ag ratio and normal VWF ratio for VWF:CB/Ag ratio the need to retain the VWF:CB assay to make a correct diagnosis of VWD 2M for its differentiation from VWD type 1. The G1415D mutation in the A1 domain is featured by decreased RIPA and decreased VWF:RCo/VWF:Ag ratio (VWD 2M) but normal values for VWF:CB/VWF:Ag, VWF:GPIbM/VWF:Ag and VWFGPIbR/VWF:Ag ratios consistent with VWD 2M. Double heterozygous P1266L/V1278I mutation in two patients and heterozygous E1292D/WT mutation in three patients in the A1 domain were diagnosed as VWD 2M or 1M associated with a secretion defect (SD). The Platelet Function Analyzer Closure Times (PFA-CT) are strongly prolonged in VWD 2A, 2B and 2M. and moderately prolonged between the upper limit of normal to 300 seconds in heterozygous mutated VWD type 1 patients.
VL  - 5
IS  - 5
ER  -

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Author Information

Jan Jacques Michiels

Department of Clinical Hematology, University Hospital and Department of Laboratory Methods, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic
Petr Smejkal

Department of Clinical Hematology, University Hospital and Department of Laboratory Methods, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic
Katarzina Mayger

Department of Haemostsis & Thrombosis, Viapath Analytics at Guy’s & St Thomas’ NHS Foundation Trust, London, UK
Gary Moore

Department of Haemostsis & Thrombosis, Viapath Analytics at Guy’s & St Thomas’ NHS Foundation Trust, London, UK
Jan Blatny

Department of Pediatric Hematology, Center for Thrombosis and Hemostasis, Children’s University Hospital, Brno, Czech Republic
Miroslav Penka

Department of Clinical Hematology, University Hospital and Department of Laboratory Methods, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic
Ulrich Budde

Central Laboratory, Asklepios Kliniken, Hamburg, Germany
Zwi Berneman

Department of Hematology and Hemostase Research Unit, University Hospital Antwerp, Edegem, Belgium
Inge Vangenechten

Department of Hematology and Hemostase Research Unit, University Hospital Antwerp, Edegem, Belgium
Alain Gadisseur

Department of Hematology and Hemostase Research Unit, University Hospital Antwerp, Edegem, Belgium

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Plain Text BibTeX RIS

APA Style

Jan Jacques Michiels, Petr Smejkal, Katarzina Mayger, Gary Moore, Jan Blatny, et al. (2019). Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. International Journal of Clinical and Experimental Medical Sciences, 5(5), 80-91. https://doi.org/10.11648/j.ijcems.20190505.14

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ACS Style

Jan Jacques Michiels; Petr Smejkal; Katarzina Mayger; Gary Moore; Jan Blatny, et al. Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. Int. J. Clin. Exp. Med. Sci. 2019, 5(5), 80-91. doi: 10.11648/j.ijcems.20190505.14

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AMA Style

Jan Jacques Michiels, Petr Smejkal, Katarzina Mayger, Gary Moore, Jan Blatny, et al. Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease. Int J Clin Exp Med Sci. 2019;5(5):80-91. doi: 10.11648/j.ijcems.20190505.14

Copy | Download

@article{10.11648/j.ijcems.20190505.14,
  author = {Jan Jacques Michiels and Petr Smejkal and Katarzina Mayger and Gary Moore and Jan Blatny and Miroslav Penka and Ulrich Budde and Zwi Berneman and Inge Vangenechten and Alain Gadisseur},
  title = {Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease},
  journal = {International Journal of Clinical and Experimental Medical Sciences},
  volume = {5},
  number = {5},
  pages = {80-91},
  doi = {10.11648/j.ijcems.20190505.14},
  url = {https://doi.org/10.11648/j.ijcems.20190505.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20190505.14},
  abstract = {A complete set of rapid activity and classical von Willebrand factor (VWF) assays for Willebrand disease (VWD) diagnosis was used in the present study to characterize VWD type 1, 2A, 2B and 2M patients due to mutations in the A1, A2 and A3 domains. The VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag ratios at cuttt off value of 0.7 separated VWD type 1 and LowVWF from VWD type 2. The results from the Brno cohort of VWD 2A patients with the G1579R mutation in the A2 domain in sixteen affected member from five families and in one case with the G1609R in the A2 domain revealed that the VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF: Ag ratios are marked decreased (range 0.03-0.27) to a similar degree as compared to VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios (range 0.03-0.27) due to the proteolytic loss of large and intermediate VWF multimers. The results in VWD 2B patients due to gain of ristocetin induced platelet agglutination (RIPA) function mutations R1306W, R1308C and R1341 in the A1 domain demonstrated that the ratios for VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag as compared to VWF:RCo/VWF:Ag ratio were markedly decreased in VWD 2B, whereas the VWF:GPIbM/VWF:Ag ratio was somewhat higher (range 0.32 to 0.36) in VWD 2M. VWD 2M patients due to loss of RIPA function mutation R1359K in the A1 domain are featured by decreased VWF ratios for WVF:RCo/Ag and VWF:GPIbR/Ag, but less decreased for the VWF:GPIbM/Ag ratio and normal VWF ratio for VWF:CB/Ag ratio the need to retain the VWF:CB assay to make a correct diagnosis of VWD 2M for its differentiation from VWD type 1. The G1415D mutation in the A1 domain is featured by decreased RIPA and decreased VWF:RCo/VWF:Ag ratio (VWD 2M) but normal values for VWF:CB/VWF:Ag, VWF:GPIbM/VWF:Ag and VWFGPIbR/VWF:Ag ratios consistent with VWD 2M. Double heterozygous P1266L/V1278I mutation in two patients and heterozygous E1292D/WT mutation in three patients in the A1 domain were diagnosed as VWD 2M or 1M associated with a secretion defect (SD). The Platelet Function Analyzer Closure Times (PFA-CT) are strongly prolonged in VWD 2A, 2B and 2M. and moderately prolonged between the upper limit of normal to 300 seconds in heterozygous mutated VWD type 1 patients.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - Superiority of the Rapid Von Willebrand Factor (VWF) VWF:GPIbR and VWF:GPIbM Assays in Type 2A, 2B and 2M Von Willebrand Disease
AU  - Jan Jacques Michiels
AU  - Petr Smejkal
AU  - Katarzina Mayger
AU  - Gary Moore
AU  - Jan Blatny
AU  - Miroslav Penka
AU  - Ulrich Budde
AU  - Zwi Berneman
AU  - Inge Vangenechten
AU  - Alain Gadisseur
Y1  - 2019/10/23
PY  - 2019
N1  - https://doi.org/10.11648/j.ijcems.20190505.14
DO  - 10.11648/j.ijcems.20190505.14
T2  - International Journal of Clinical and Experimental Medical Sciences
JF  - International Journal of Clinical and Experimental Medical Sciences
JO  - International Journal of Clinical and Experimental Medical Sciences
SP  - 80
EP  - 91
PB  - Science Publishing Group
SN  - 2469-8032
UR  - https://doi.org/10.11648/j.ijcems.20190505.14
AB  - A complete set of rapid activity and classical von Willebrand factor (VWF) assays for Willebrand disease (VWD) diagnosis was used in the present study to characterize VWD type 1, 2A, 2B and 2M patients due to mutations in the A1, A2 and A3 domains. The VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag ratios at cuttt off value of 0.7 separated VWD type 1 and LowVWF from VWD type 2. The results from the Brno cohort of VWD 2A patients with the G1579R mutation in the A2 domain in sixteen affected member from five families and in one case with the G1609R in the A2 domain revealed that the VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF: Ag ratios are marked decreased (range 0.03-0.27) to a similar degree as compared to VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios (range 0.03-0.27) due to the proteolytic loss of large and intermediate VWF multimers. The results in VWD 2B patients due to gain of ristocetin induced platelet agglutination (RIPA) function mutations R1306W, R1308C and R1341 in the A1 domain demonstrated that the ratios for VWF:GPIbM/VWF:Ag and VWF:GPIbR/VWF:Ag as compared to VWF:RCo/VWF:Ag ratio were markedly decreased in VWD 2B, whereas the VWF:GPIbM/VWF:Ag ratio was somewhat higher (range 0.32 to 0.36) in VWD 2M. VWD 2M patients due to loss of RIPA function mutation R1359K in the A1 domain are featured by decreased VWF ratios for WVF:RCo/Ag and VWF:GPIbR/Ag, but less decreased for the VWF:GPIbM/Ag ratio and normal VWF ratio for VWF:CB/Ag ratio the need to retain the VWF:CB assay to make a correct diagnosis of VWD 2M for its differentiation from VWD type 1. The G1415D mutation in the A1 domain is featured by decreased RIPA and decreased VWF:RCo/VWF:Ag ratio (VWD 2M) but normal values for VWF:CB/VWF:Ag, VWF:GPIbM/VWF:Ag and VWFGPIbR/VWF:Ag ratios consistent with VWD 2M. Double heterozygous P1266L/V1278I mutation in two patients and heterozygous E1292D/WT mutation in three patients in the A1 domain were diagnosed as VWD 2M or 1M associated with a secretion defect (SD). The Platelet Function Analyzer Closure Times (PFA-CT) are strongly prolonged in VWD 2A, 2B and 2M. and moderately prolonged between the upper limit of normal to 300 seconds in heterozygous mutated VWD type 1 patients.
VL  - 5
IS  - 5
ER  -

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