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

Castaman, Giancarlo; Lethagen, Stefan LU ; Federici, Augusto B; Tosetto, Alberto; Goodeve, Anne; Budde, Ulrich; Batlle, Javier; Meyer, Dominique; Mazurier, Claudine and Fressinaud, Edith, et al. (2008) In Blood 111(7). p.3531-3539
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... (More)
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. (Less)
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Blood
volume
111
issue
7
pages
3531 - 3539
publisher
American Society of Hematology
external identifiers
  • wos:000254569300040
  • scopus:43549097149
ISSN
1528-0020
DOI
10.1182/blood-2007-08-109231
language
English
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yes
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3a6e4b8c-bc31-4b94-9be4-bc116ee03e3c (old id 1182688)
date added to LUP
2008-09-19 14:29:13
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2017-11-05 03:32:37
@article{3a6e4b8c-bc31-4b94-9be4-bc116ee03e3c,
  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.},
  author       = {Castaman, Giancarlo and Lethagen, Stefan and Federici, Augusto B and Tosetto, Alberto and Goodeve, Anne and Budde, Ulrich and Batlle, Javier and Meyer, Dominique and Mazurier, Claudine and Fressinaud, Edith and Goudemand, Jenny and Eikenboom, Jeroen and Schneppenheim, Reinhard and Ingerslev, Jorgen and Vorlova, Zdena and Habart, David and Holmberg, Lars and Pasi, John and Hill, Frank and Peake, Ian and Rodeghiero, Francesco},
  issn         = {1528-0020},
  language     = {eng},
  number       = {7},
  pages        = {3531--3539},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD},
  url          = {http://dx.doi.org/10.1182/blood-2007-08-109231},
  volume       = {111},
  year         = {2008},
}