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

Blood - Tập 111 - Trang 3531-3539 - 2008
Giancarlo Castaman1, Stefan Lethagen2, Augusto B. Federici3, Alberto Tosetto1, Anne Goodeve4, Ulrich Budde5, Javier Batlle6, Dominique Meyer7, Claudine Mazurier8, Edith Fressinaud9, Jenny Goudemand10, Jeroen Eikenboom11, Reinhard Schneppenheim12, Jorgen Ingerslev13, Zdena Vorlova14, David Habart14, Lars Holmberg15, John Pasi16, Frank Hill17, Ian Peake4
1Department of Hematology, San Bortolo Hospital, Vicenza, Italy
2Department for Coagulation Disorders, University of Lund, Malmö, Sweden and Center for Hemostasis and Thrombosis, Copenhagen University Hospital, Copenhagen, Denmark;
3Hemophilia and Thrombosis Centre, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Maggiore Policlinico Hospital, Mangiagalli Regina Elena and University of Milan, Milan, Italy;
4The Academic Unit of Haematology, University of Sheffield, Sheffield, United Kingdom;
5Coagulation Laboratory, Hamburg, Germany
6Servicio de Hematologia y Hemoterapia, Hospital Teresa Herrera, La Coruna, Spain
7Institut National de la Santè et de la Recherche Médicale, Inserm U143, Paris, France;
8Laboratoire Français du Fractionnement et des Biotechnologies, Lille, France
9INSERM, Nantes, France
10University of Lille, Lille, France
11Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
12University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany
13Centre for Hemophilia and Thrombosis, University Hospital Skejby, Aarhus, Denmark;
14Institute of Hematology and Blood Transfusion, Prague, Czech Republic
15Department of Pediatrics, University of Lund, Lund, Sweden
16Department of Pathology, Leicester Royal Infirmary, Leicester, United Kingdom; and
17Department of Hematology, Children's Hospital, Birmingham, United Kingdom

Tóm tắt

Abstract

We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF:RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P = .002). Patients with mutations at codons 1130 and 1205 in the D′-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.


Tài liệu tham khảo

Rodeghiero, 1987, Epidemiological investigation of the prevalence of von Willebrand's disease., Blood, 69, 454, 10.1182/blood.V69.2.454.454 Werner, 1993, Prevalence of von Willebrand disease in children: a multiethnic study., J Pediatr, 123, 893, 10.1016/S0022-3476(05)80384-1 Rodeghiero, 2005, Treatment of von Willebrand disease., Semin Hematol, 42, 29, 10.1053/j.seminhematol.2004.10.001 Kaufmann, 2000, Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP., Blood, 106, 107 Castaman, 2003, Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment., Haematologica, 88, 94 Rodeghiero, 1988, Hyper-responsiveness to DDAVP for patients with type I von Willebrand's disease and normal intra-platelet von Willebrand factor., Eur J Haematol, 40, 163, 10.1111/j.1600-0609.1988.tb00815.x Lethagen, 1987, Intranasal and intravenous administration of desmopressin: effect on FVIII/vWF, pharmacokinetics and reproducibility., Thromb Haemost, 58, 1033, 10.1055/s-0038-1646050 Federici, 2004, Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study., Blood, 103, 2032, 10.1182/blood-2003-06-2072 Rodeghiero, 1989, Consistency of responses to repeated DDAVP infusions in patients with von Willebrand's disease and hemophilia A., Blood, 74, 1997, 10.1182/blood.V74.6.1997.1997 Casonato, 2002, Reduced von Willebrand factor survival in type Vicenza von Willebrand disease., Blood, 99, 180, 10.1182/blood.V99.1.180 Castaman, 2006, Factor VIII and von Willebrand factor changes after desmopressin and during pregnancy in type 2M von Willebrand disease Vicenza: a prospective study comparing patients with single (R1205H) and double (R1205H-M740I) defect., J Thromb Haemost, 4, 357, 10.1111/j.1538-7836.2006.01706.x Schooten, 2005, Cysteine-mutations in von Willebrand factor associated with increased clearance., J Thromb Haemost, 3, 2228, 10.1111/j.1538-7836.2005.01571.x Haberichter, 2006, Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decresed survival., Blood, 108, 3344, 10.1182/blood-2006-04-015065 Goodeve, 2007, 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)., Blood, 109, 112, 10.1182/blood-2006-05-020784 Tosetto, 2006, A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD)., J Thromb Haemost, 4, 766, 10.1111/j.1538-7836.2006.01847.x Eikenboom, 2006, 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, 4, 774, 10.1111/j.1538-7836.2006.01823.x James, 2007, The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study., Blood, 109, 145, 10.1182/blood-2006-05-021105 Cumming, 2006, An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease., Thromb Haemost, 96, 630, 10.1160/TH06-07-0383 Revel-Vilk, 2003, Desmopressin (DDAVP) responsiveness in children with von Willebrand disease., J Pediatr Hematol Oncol, 25, 874, 10.1097/00043426-200311000-00010 Castaman, 2002, The elusive pathogenesis of von Willebrand disease Vicenza., Blood, 99, 4243, 10.1182/blood.V99.11.4243 Sadler, 2006, Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor., J Thromb Haemost, 4, 2103, 10.1111/j.1538-7836.2006.02146.x Mannucci, 1988, von Willebrand disease “Vicenza” with larger-than-normal (supranormal) von Willebrand factor multimers., Blood, 71, 65, 10.1182/blood.V71.1.65.65 Castaman, 2000, Autosomal dominant type 1 von Willebrand disease due to G3639T mutation (C1130F) in exon 26 of von Willebrand factor gene: description of five Italian families and evidence for a founder effect., Br J Haematol, 108, 876, 10.1046/j.1365-2141.2000.01944.x Mannucci, 1985, Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor., Blood, 66, 796, 10.1182/blood.V66.4.796.796 Eikenboom, 1996, Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor., Blood, 88, 2433, 10.1182/blood.V88.7.2433.bloodjournal8872433
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Blood

Tập 111

3531-3539

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