title: Prothrombin fragment 1+2 and thrombin-antithrombin complex levels in patients with inherited APC resistance due to factor V Leiden mutation.
abstract: Inherited activated protein C (APC) resistance is a newly described pathological condition associated with familial thrombophilia. A recent report on family with APC resistance showed increased levels of prothrombin fragment 1 + 2 (F1 + 2) in the affected individuals. No data concerning thrombin-antithrombin complex (TAT) levels in patients with inherited APC resistance are presently available. The aim of this study was to assess the plasma levels of F1 + 2 and TAT in patients with inherited APC resistance due to factor V (F.V) Leiden mutation and to evaluate F1 + 2 and TAT levels in symptomatic and asymptomatic patients with the defect ('carriers') as compared to their family members having no evidence of F.V Leiden mutation ('non-carriers'). One hundred and twenty-nine individuals belonging to 30 families with inherited APC resistance due to F.V Leiden mutation were studied. F1 + 2 and TAT levels were determined using two commercially available ELISA kits and cut-off values were defined as the higher limits of normal ranges obtained in healthy volunteers. Out of the 129 family members investigated, 36 were non-carriers, 85 were heterozygous and eight homozygous for F.V Leiden mutation. Thrombosis had occurred in 2/36 (6%) non-carriers, in 36/85 (42.3%) heterozygous and in 5/8 (63%) homozygous. Median levels of F1 + 2 and TAT were above cutoff values in carriers, whereas they were below in non-carriers. An overall percentage of 68.8% of carriers exhibited F1 +2 levels above the cut-off value as compared to 38.9% of non-carriers. For TAT, an overall percentage of 63.4% of carriers presented with levels above the cut-off compared with 28% of non-carriers. In conclusion, patients with inherited F.V Leiden mutation may exhibit increased levels of F1 + 2 and TAT. There are no differences in F1 + 2 and TAT median levels among symptomatic and asymptomatic carriers. The percentage of carriers of F.V Leiden with levels of F1 + 2 and TAT above cut-off appears to be higher than that found in other clotting inhibitors defects and in this respect the defect might be considered different. However, these findings and the presence of high percentage of non-carriers presenting with increased F1 + 2 and TAT levels may suggest the possible coexistence in these families of other unknown defects predisposing to thrombosis.
authors.affiliation: Institute of Medical Semeiotics, University of Padua Medical School, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Simioni
authors.forename: L
authors.initials: L
authors.lastname: Scarano
authors.forename: S
authors.initials: S
authors.lastname: Gavasso
authors.forename: C
authors.initials: C
authors.lastname: Sardella
authors.forename: B
authors.initials: B
authors.lastname: Girolami
authors.forename: A
authors.initials: A
authors.lastname: Scudeller
authors.forename: A
authors.initials: A
authors.lastname: Girolami
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D005165:Factor V / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D017354:Point Mutation; D011486:Protein C; D011516:Prothrombin / Q000032:analysis*; D013927:Thrombosis / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011486:Protein C; C045879:prothrombin fragment 1.2; D005165:Factor V; D011516:Prothrombin