title: Soluble endothelial protein C receptor (sEPCR) levels and venous thromboembolism in carriers of two dysfunctional protein C variants.
abstract: The role of the A3 haplotype and soluble endothelial protein C receptor (sEPCR) plasma levels in predisposing the carriers of two peculiar dysfunctional protein C (PC) variants (PC Arg-1-->Cys and PC Arg-1-->Leu, also known as PC Padua(2) and PC Padua(3), respectively) to venous thromboembolism (VTE) has been evaluated. The levels of sEPCR have been assessed in family members during 6 years of follow-up and correlated to the presence of the A3 haplotype. Individuals who carried both a dysfunctional PC and the A3 haplotype and presenting with high levels of sEPCR experienced severe VTE at young age. The increased plasma levels of sEPCR were not related to excessive thrombin generation. Carriers of the A3 haplotype showed levels of sEPCR above 135 ng/ml (80th percentile of the distribution in healthy subjects), which remained elevated during the follow-up. In non-carriers of the A3 haplotype, sEPCR levels remained persistently around 100 ng/ml or lower. In conclusion, we have observed that elevated sEPCR plasma levels and the concomitant presence of the A3 haplotype of EPCR gene are associated with severe thrombotic manifestations in carriers of two dysfunctional PC variants. Whether high plasma levels of sEPCR and/or the presence of the A3 haplotype increase the risk of thrombosis in carriers of other PC defects or thrombophilic conditions remains to be clarified.
authors.affiliation: Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy. paolo.simioni@unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Olivier
authors.initials: O
authors.lastname: Morboeuf
authors.forename: Giulio
authors.initials: G
authors.lastname: Tognin
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gavasso
authors.forename: Daniela
authors.initials: D
authors.lastname: Tormene
authors.forename: Barry
authors.initials: B
authors.lastname: Woodhams
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagnan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015791:HLA-A3 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000097:blood*; D012306:Risk; D012995:Solubility; D020246:Venous Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*
chemical_list: D001779:Blood Coagulation Factors; D015791:HLA-A3 Antigen; D011486:Protein C; D011956:Receptors, Cell Surface; C091963:activated protein C receptor; C513433:protein C Padua2, human; C453259:protein C Padua3