title: "Pseudo homozygous" activated protein C resistance due to double heterozygous factor V defects (factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: report of two cases belonging to two unrelated kindreds.
abstract: Two unrelated patients belonging to two Italian kindreds with a history of thrombotic manifestations were found to have a double heterozygous defect of factor V (F. V), namely type I quantitative F.V defect and F.V Leiden mutation. Although DNA analysis confirmed the presence of a heterozygous F.V Leiden mutation, the measurement of the responsiveness of patients' plasma to addition of activated protein C (APC) gave results similar to those found in homozygous defects. It has been recently reported in a preliminary form that the coinheritance of heterozygous F. V Leiden mutation and type I quantitative F. V deficiency in three individuals belonging to the same family resulted in the so-called pseudo homozygous APC resistance with APC sensitivity ratio (APC-SR) typical of homozygous F.V Leiden mutation. In this study we report two new cases of pseudo homozygous APC resistance. Both patients experienced thrombotic manifestations. It is likely that the absence of normal F.V, instead of protecting from thrombotic risk due to heterozygous F.V Leiden mutation, increased the predisposition to thrombosis since the patients became, in fact, pseudo-homozygotes for APC resistance. DNA-analysis is the only way to genotype a patient and is strongly recommended to confirm a diagnosis of homozygous F.V Leiden mutation also in patients with the lowest values of APC-SR. It is to be hoped that no patient gets a diagnosis of homozygous F.V Leiden mutation based on the APC-resistance test, especially when the basal clotting tests, i.e., PT and aPTT; are borderline or slightly prolonged.
authors.affiliation: Institute of Medical Semelotics, University of Padua Medical School, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Simioni
authors.forename: A
authors.initials: A
authors.lastname: Scudeller
authors.forename: P
authors.initials: P
authors.lastname: Radossi
authors.forename: S
authors.initials: S
authors.lastname: Gavasso
authors.forename: B
authors.initials: B
authors.lastname: Girolami
authors.forename: D
authors.initials: D
authors.lastname: Tormene
authors.forename: A
authors.initials: A
authors.lastname: Girolami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011486:Protein C / Q000494:pharmacology*; D013927:Thrombosis / Q000235:genetics*
chemical_list: D011486:Protein C; C095381:factor V Leiden; D005165:Factor V