Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications.
BACKGROUND
Mutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD).


METHODS
Eight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities, not described in earlier studies.


RESULTS
The patients showed notably low levels of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding (VWF:CB), and a reduced ristocetin-induced 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.


CONCLUSIONS
We 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.
Pérez-Rodríguez
Almudena
A
Servicio de Hematología y Hemoterapia, Complexo Hospitalario, Universitario Juan Canalejo (Edificio Hospital Materno Infantil), Carretera del Pasaje s/n, La Coruña, Spain.
García-Rivero
Aranzazu
A
Lourés
Esther
E
López-Fernández
Maria Fernanda
MF
Rodríguez-Trillo
Angela
A
Batlle
Javier
J
D001792:Blood Platelets / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage; D004587:Electrophoresis, Agar Gel; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009154:Mutation; D010641:Phenotype; D055503:Protein Multimerization / Q000187:drug effects; D013997:Time Factors; D014842:von Willebrand Diseases / Q000097:blood / Q000145:classification / Q000235:genetics*; D014841:von Willebrand Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin