VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease

被引：89

作者：

Eikenboom, Jeroen ^{[1
]}

Federici, Augusto B. ^{[2
,3
]}

Dirven, Richard J. ^{[1
]}

Castaman, Giancarlo ^{[4
]}

Rodeghiero, Francesco ^{[4
]}

Budde, Ulrich ^{[5
]}

Schneppenheim, Reinhard ^{[6
]}

Batlle, Javier ^{[7
]}

Canciani, Maria Teresa ^{[2
,3
]}

Goudemand, Jenny ^{[8
]}

Peake, Ian ^{[9
]}

Goodeve, Anne ^{[9
]}

机构：

[1] Leiden Univ, Einthoven Lab Expt Vasc Med, Dept Thrombosis & Hemostasis, Med Ctr, NL-2300 RC Leiden, Netherlands

[2] Fdn IRCCS Ca Granda Maggiore Policlin Hosp, AB Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy

[3] Univ Milan, Milan, Italy

[4] San Bortolo Hosp, Dept Hematol, Vicenza, Italy

[5] Medilys Lab Gesell mbH, Hamostaseol, Hamburg, Germany

[6] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[7] Hosp Teresa Herrera, Serv Hematol & Hemoterapia, La Coruna, Spain

[8] Univ Lille, Lille, France

[9] Univ Sheffield, Haemostasis Res Grp, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England

来源：

BLOOD | 2013年 / 121卷 / 12期

关键词：

CLINICAL MARKERS; QUANTITATIVE-ANALYSIS; DIAGNOSIS; MANAGEMENT; MUTATIONS; SECRETION; GENOTYPE; FAMILIES; CLEARANCE; PHENOTYPE;

D O I：

10.1182/blood-2012-09-455089

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

During posttranslational modifications of von Willebrand factor (VWF), the VWF propeptide (VWFpp) is cleaved. The ratio between VWFpp and VWF antigen (VWF:Ag) and the ratio between factor VIII (FVIII:C) and VWF:Ag may be used to assess synthesis and clearance of VWF. We analyzed the contribution of VWFpp and ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag in the pathophysiological characterization of type 1 von Willebrand disease (VWD) in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD) study. The VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were increased among patients compared with unaffected family members and healthy controls. The VWFpp/VWF:Ag ratio was higher in individuals heterozygous for missense mutations than in those heterozygous for null alleles. In contrast, the FVIII:C/VWF:Ag ratio was highest among heterozygotes for VWF null alleles. The ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag indicate that the pathophysiological mechanisms of type 1 VWD include reduced production and accelerated clearance of VWF, but that often a combination of bothmechanisms is implicated.

引用

页码：2336 / 2339

页数：4

共 23 条

[1] Quantitative analysis of von Willebrand factor propeptide release in vivo: Effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans [J].

Borchiellini, A ;

Fijnvandraat, K ;

tenCate, JW ;

Pajkrt, D ;

vanDeventer, SJH ;

Pasterkamp, G ;

MeijerHuizinga, F ;

ZwartHuinink, L ;

Voorberg, J ;

vanMourik, JA .

BLOOD, 1996, 88 (08) :2951-2958

[2] 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].

Budde, U. ;

Schneppenheim, R. ;

Eikenboom, J. . ;

Goodeve, A. ;

Will, K. ;

Drewke, E. ;

Castaman, G. ;

Rodeghiero, F. ;

Federici, A. B. ;

Batlle, J. . ;

Perez, A. ;

Meyer, D. ;

Mazurier, C. ;

Goudemand, J. ;

Ingerslev, J. ;

Habart, D. ;

Vorlova, Z. ;

Holmberg, L. ;

Lethagen, S. ;

Pasi, J. ;

Hill, F. ;

Peake, I. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2008, 6 (05) :762-771

[3] Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD [J].

Castaman, Giancarlo ;

Lethagen, Stefan ;

Federici, Augusto B. ;

Tosetto, Alberto ;

Goodeve, Anne ;

Budde, Ulrich ;

Batlle, Javier ;

Meyer, Dominique ;

Mazurier, Claudine ;

Fressinaud, Edith ;

Goudemand, Jenny ;

Eikenboom, Jeroen ;

Schneppenheim, Reinhard ;

Ingerslev, Jorgen ;

Vorlova, Zdena ;

Habart, David ;

Holmberg, Lars ;

Pasi, John ;

Hill, Frank ;

Peake, Ian ;

Rodeghiero, Francesco .

BLOOD, 2008, 111 (07) :3531-3539

[4] 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].

Eikenboom, J ;

Van Marion, V ;

Putter, H ;

Goodeve, A ;

Rodeghiero, F ;

Castaman, G ;

Federici, AB ;

Batlle, J ;

Meyer, D ;

Mazurier, C ;

Goudemand, J ;

Schneppenheim, R ;

Budde, U ;

Ingerslev, J ;

Vorlova, Z ;

Habart, D ;

Holmberg, L ;

Lethagen, S ;

Pasi, J ;

Hill, F ;

Peake, I .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2006, 4 (04) :774-782

[5] Expression of 14 von Willebrand factor mutations identified in patients with type 1 von Willebrand disease from the MCMDM-1VWD study [J].

Eikenboom, J. ;

Hilbert, L. ;

Ribba, A. S. ;

Hommais, A. ;

Habart, D. ;

Messenger, S. ;

Al-Buhairan, A. ;

Guilliatt, A. ;

Lester, W. ;

Mazurier, C. ;

Meyer, D. ;

Fressinaud, E. ;

Budde, U. ;

Will, K. ;

Schneppenheim, R. ;

Obser, T. ;

Marggraf, O. ;

Eckert, E. ;

Castaman, G. ;

Rodeghiero, F. ;

Federici, A. B. ;

Batlle, J. ;

Goudemand, J. ;

Ingerslev, J. ;

Lethagen, S. ;

Hill, F. ;

Peake, I. ;

Goodeve, A. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 (08) :1304-1312

[6]

Eikenboom JCJ, 2002, THROMB HAEMOSTASIS, V87, P252

[7] Phenotype and genotype of a cohort of families historically diagnosed with type 1 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].

Goodeve, Anne ;

Eikenboom, Jeroen ;

Castaman, Giancarlo ;

Rodeghiero, Francesco ;

Federici, Augusto B. ;

Batlle, Javier ;

Meyer, Dominique ;

Mazurier, Claudine ;

Goudemand, Jenny ;

Schneppenheim, Reinhard ;

Budde, Ulrich ;

Ingerslev, Jorgen ;

Habart, David ;

Vorlova, Zdena ;

Holmberg, Lars ;

Lethagen, Stefan ;

Pasi, John ;

Hill, Frank ;

Soteh, Mohammad Hashemi ;

Baronciani, Luciano ;

Hallden, Christer ;

Guilliatt, Andrea ;

Lester, Will ;

Peake, Ian .

BLOOD, 2007, 109 (01) :112-121

[8] Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD) [J].

Haberichter, Sandra L. ;

Castarnan, Giancarlo ;

Budde, Ulrich ;

Peake, Ian ;

Goodeve, Anne ;

Rodeghiero, Francesco ;

Federici, Augusto B. ;

Batlle, Javier ;

Meyer, Dominique ;

Mazurier, Claudine ;

Goudemand, Jenny ;

Eikenboom, Jeroen ;

Schneppenheim, Reinhard ;

Ingerslev, Jorgen ;

Vorlova, Zdena ;

Habart, David ;

Holmberg, Lars ;

Lethagen, Stefan ;

Pasi, John ;

Hill, Frank G. H. ;

Montgomery, Robert R. .

BLOOD, 2008, 111 (10) :4979-4985

[9] Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival [J].

Haberichter, Sandra L. ;

Balistreri, Michael ;

Christopherson, Pamela ;

Morateck, Patricia ;

Gavazova, Stefana ;

Bellissimo, Daniel B. ;

Manco-Johnson, Marilyn J. ;

Gill, Joan Cox ;

Montgomery, Robert R. .

BLOOD, 2006, 108 (10) :3344-3351

[10] Polymorphic variation within the VWF gene contributes to the failure to detect mutations in patients historically diagnosed with type 1 von Willebrand disease from the MCMDM-1VWD cohort [J].

Hampshire, Daniel J. ;

Burghel, George J. ;

Goudemand, Jenny ;

Bouvet, Laura C. S. ;

Eikenboom, Jeroen C. J. ;

Schneppenheim, Reinhard ;

Budde, Ulrich ;

Peake, Ian R. ;

Goodeve, Anne C. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (12) :2163-2165

← 1 2 3 →