title: An underestimated combination of opposites resulting in enhanced thrombotic tendency.
abstract: Heterozygous carriers of factor V (FV) Leiden who also carry FV deficiency often develop venous thromboembolism, but the thrombosis risk associated with this rare condition (pseudohomozygous activated protein C resistance) is still unclear. The thrombosis risk of genetically characterized pseudohomozygotes (n = 6) was compared with that of FV Leiden heterozygotes (n = 683) and homozygotes (n = 50) recruited within a large cohort study on familial thrombophilia. Both thrombin generation and Kaplan-Meier thrombosis-free survival analyses were performed in different FV genotype groups. FV Leiden pseudohomozygotes showed significantly higher thrombosis risk than heterozygotes. The thrombin generation test in pseudohomozygotes showed a pattern similar to homozygotes. Accordingly, early thrombotic manifestations occurred in pseudohomozygotes at a similar rate as in homozygotes. Thus, failure to recognize FV deficiency in FV Leiden heterozygotes may result in an underestimate of the thrombosis risk and inadequate management of affected patients.
authors.affiliation: Department of Medical and Surgical Sciences, Second 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: Elisabetta
authors.initials: E
authors.lastname: Castoldi
authors.forename: Barbara
authors.initials: B
authors.lastname: Lunghi
authors.forename: Daniela
authors.initials: D
authors.lastname: Tormene
authors.forename: Jan
authors.initials: J
authors.lastname: Rosing
authors.forename: Francesco
authors.initials: F
authors.lastname: Bernardi
mesh_terms: D020016:Activated Protein C Resistance / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011486:Protein C / Q000378:metabolism; D012306:Risk; D013923:Thromboembolism; D013927:Thrombosis / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D011486:Protein C; C095381:factor V Leiden; D005165:Factor V