PROTHROMBIN FRAGMENT-1-ANTITHROMBIN COMPLEX LEVELS IN PATIENTS WITH INHERITED APC RESISTANCE DUE TO FACTOR-V LEIDEN MUTATION(2 AND THROMBIN)

Inherited activated protein C (APC) resistance is a newly described pa thological condition associated with familial thrombophilia. A recent report on a family with APC resistance showed increased levels of prot hrombin fragment 1+2 (F1+2) in the affected individuals. No data conce rning thrombin-antithrombin complex (TAT) levels in patients with inhe rited APC resistance are presently available. The aim of this study wa s to assess the plasma levels of F1+2 and TAT in patients with inherit ed APC resistance due to factor V (F.V) Leiden mutation and to evaluat e F1+2 and TAT levels in symptomatic and asymptomatic patients with th e defect ('carriers') as compared to their family members having no ev idence of F.V Leiden mutation ('non-carriers'). One hundred and twenty -nine individuals belonging to 30 families with inherited APC resistan ce due to F.V Leiden mutation were studied. F1+2 and TAT levels were d etermined using two commercially available ELISA kits and cut-off valu es were defined as the higher limits of normal ranges obtained in heal thy volunteers. Out of the 129 family members investigated, 36 were no n-carriers, 85 were heterozygous and eight homozygous for F.V Leiden m utation. 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-carri ers. For TAT, an overall percentage of 63.4% of carriers presented wit h levels above the cut-off compared with 28% of non-carriers. In concl usion, patients with inherited F.V Leiden mutation may exhibit increas ed levels of F1+2 and TAT. There are no differences in F1+2 and TAT me dian levels among symptomatic and asymptomatic carriers. The percentag e 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 defe cts and in this respect the defect might be considered different. Howe ver, these findings and the presence of a high percentage of non-carri ers presenting with increased F1+2 and TAT levels may suggest the poss ible coexistence in these families of other unknown defects predisposi ng to thrombosis.