Platelet membrane glycoprotein polymorphisms do not influence the clinical expressivity of von Willebrand disease type 1

Jaime Pereira; Teresa Quiroga; Elisa M. Pereira; María Morales; Manuela Goycoolea; Patricia Hidalgo; Carolina Prieto; Diego Mezzano

doi:10.1160/TH03-03-0135

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(06): 1135-1140
DOI: 10.1160/TH03-03-0135

Platelets and Blood Cells

Schattauer GmbH

Platelet membrane glycoprotein polymorphisms do not influence the clinical expressivity of von Willebrand disease type 1

Jaime Pereira

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Teresa Quiroga

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Elisa M. Pereira

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

María Morales

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Manuela Goycoolea

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Patricia Hidalgo

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Carolina Prieto

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

,

Diego Mezzano

¹Departments of Haematology-Oncology and Clinical Laboratory, School of Medicine, Catholic University of Chile and Pediatric Hemophilia Ctr., Roberto del Río Hospital, Santiago, Chile

› Author Affiliations

Abstract

Summary

Von Willebrand disease (VWD) is characterized by a significant variation in bleeding symptoms among patients with similar laboratory profiles and equivalent plasma levels of von Willebrand factor (VWF) activities. Considering the recent suggestion that platelet membrane glycoprotein polymorphisms (PltGPs) may play a role as modulators of thromboembolic or haemorrhagic diseases, we investigated the role of different PltGPs and GPVI content in the clinical expression of patients with VWD type 1. The diagnosis of VWD (n = 76) was based on laboratory findings (VWF:Ag, VWF:RCo, VWF:CB, FVIII:C, and multimer analysis), family and personal history of bleeding. All patients were interviewed using a standardized questionnaire, and classified into two categories: bleeders (unequivocal bleeding tendency, n = 53) and non bleeders (absence of bleeding symptoms, n = 23). PltGPs, HPA-1, 2 and 5 and C807T of GPIa were determined by fluorophore-labelled hybridization probes on a LightCycler^TM. GPVI content was measured by western blotting.

VWF:Ag, VWF:RCo, VWF:CB and FVIII:C levels were not significantly different between symptomatic and asymptomatic patients. There were no differences in the genotype distribution and allele frequencies between bleeders and non bleeders for the platelet alloantigen systems HPA-1, 2, 5 and the GPIa C807T polymorphism. The levels of platelet GPVI were similar in symptomatic and asymptomatic VWD patients (109.6 ± 58.4 vs 114.1 ± 52.5, respectively; p: 0.77). These results show that PltGPs HPA-1, 2 and 5 or the C807T dimorphism of GPIa do not influence the clinical expressivity of VWD type 1. The wide variation in GPVI content was not associated with the severity of bleeding in the patients. Other genetic factors that may contribute to the variable expressivity of VWD type 1 should be investigated.

Keywords

von Willebrand disease - platelet glycoproteins - polymorphisms - bleeding diathesis

Full Text

References

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