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.

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Blood

Tập 111

3531-3539

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