Heterogeneity of type IIA von Willebrand Disease: Studies with protease inhibitor

Batlle, J.; López-Fernández, Maŕıa; Campos, M.; Justiça, Benvindo; Pardo, A; Díaz-Cremades, Juan; Kasper, Carol K.; Ruggeri, Zaverio M.; Zimmerman, Theodore S.

doi:10.1016/0049-3848(86)91625-7

Cited by 14 publications

(13 citation statements)

References 5 publications

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“…It suggests that the molecular abnormality present in the patients favors a proteolytic fragmentation different from that occurring for normal VWF and for VWD type 2A (IIA). 29 These findings are in agreement with the potential Figure 5. DDAVP responses in plasmas of a normal subject and a patient with C1149R mutation.…”

Section: Discussionsupporting

confidence: 82%

Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

Pérez‐Rodríguez

García-Rivero²,

Lourés³

et al. 2009

Haematologica

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BackgroundMutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD). Design and MethodsEight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities, not described in earlier studies. ResultsThe patients showed notably low levels of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding (VWF:CB), and a reduced ristocetininduced platelet aggregation (RIPA). VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios were lower than 0.7. At basal conditions, all the VWF multimers were decreased in plasma, with a clearly lower relative proportion of the high molecular weight VWF multimers (HMWM). In high-resolution agarose gels, a large decrease in the relative proportions of the satellite bands was seen. The patients had a brief good response to desmopressin (DDAVP) administration, but the released VWF half-life was shorter than normal, indicating an accelerated clearance of their VWF. Platelet VWF was abnormal. ConclusionsWe conclude from the results obtained in these patients for plasma phenotypic data that this mutation should be classified as a VWD type 2A (IIE). DDAVP therapy may be somewhat helpful for this mutation, at least for mild to moderate bleeding. These data provide evidence that for VWD classification factors other than basal VWF, such as DDAVP response and platelet VWF, should be considered.

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Section: Discussionsupporting

confidence: 82%

Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

Pérez‐Rodríguez

García-Rivero²,

Lourés³

et al. 2009

Haematologica

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“…It has been reported that some patients with type 2A VWD respond better than others to DDAVP. 20,21 However, these reports predated knowledge of gene defects and the description of different mechanisms of type 2A VWD (intracellular processing defects vs increased extracellular proteolysis). [10][11][12] In this study the changes of FVIII/VWF activities, including the multimeric pattern, were documented using 4 patient examples, 2 with the features of group 1 (S1506L and V1665E) and 2 with the features of group 2 (R1597W and G1629R), as established by expression studies.…”

Section: Discussionmentioning

confidence: 99%

Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study

Federici

Mazurier

Berntorp³

et al. 2004

Blood

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2N (n ‫؍‬ 4 of 4), but in none of those with type 1 VWD. Genotype provided more information than phenotype in predicting individual responses to DDAVP only in patients with 2A and 2N VWD. This prospective study showed that the rate of biologic response to DDAVP is relatively low not only in type 2 but also in type 1 VWD when uniform and stringent criteria for patient selection and responsiveness are applied.

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“…Recently, it has been suggested that the abnormal vWF pattern seen in type IIA vWD is due to a proteolytic phenomenon [1,6], Since in our study AHF concentrate vWF showed an abnormal multimeric structure with the fastest moving component of each triplet disproportionally increased, resembling that observed in type IIA vWD [18], and also taking into account that these concentrates come from healthy donor plasma which show a normal multimeric and triplet pattern which persist in the ordi nary cryoprecipitate, it is conceivable that the abnormal structure of those concentrates is a consequence of a proteolytic attack on vWF, which could induce degrada tion of the largest multimers to the smaller forms. The heterogeneity seen between the five preparations ana lyzed in our study points to a differing degree of proteo lysis during the purification process.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Multimeric Structure and Ristocetin-Induced Binding to Platelets of Von Willebrand Factor Present in Cryoprecipitate and Different Factor VIII Concentrates

López-Fernández¹,

López-Berges²,

Corral³

et al. 1987

Vox Sanguinis

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The multimeric structure of von Willebrand factor (vWF) and its ristocetin-induced binding to platelets, using a simple and very sensitive radiomonoclonal antibody-labeled vWF method, was compared in normal plasma, single-donor cryoprecipitate (CP) and five different antihemophilic factor (AHF) concentrates. All the AFIF showed a lack of larger vWF multimers, an abnormal ‘triplet’ pattern, and much lower vWF binding to platelets than that of plasma or CP, vWF being the lowest for those with a lesser proportion of larger vWF multimers. These results suggest that the combination of vWF multimeric analysis and the radiomonoclonal-labeled vWF method may be very useful in the assessment of AHF preparations.

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Heterogeneity of type IIA von Willebrand Disease: Studies with protease inhibitor

Cited by 14 publications

References 5 publications

Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study

Assessment of Multimeric Structure and Ristocetin-Induced Binding to Platelets of Von Willebrand Factor Present in Cryoprecipitate and Different Factor VIII Concentrates

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