Prothrombin activity and concentration in healthy subjects with and without the prothrombin G20210A mutation

A common mutation in the prothrombin gene (G20210A) is associated with elev ated prothrombin levels and thrombosis. The pathomechanism related to the G 20210A mutation is currently not understood and the interdependence of prot hrombin activity and prothrombin concentration in plasma is still poorly de fined. Six of 191 blood donors examined in the present study carried the pr othrombin allele G20210A. Despite the small number of cases, plasma samples from these individuals had significantly higher prothrombin activities tha n wild type carriers (131+/-7.1% vs. 114+/-18.3%, P=0.017), whereas their p rothrombin concentrations-although elevated-did not differ significantly fr om wild type (122+/-30.7 mg/L vs. 107+/-20.6 mg/L, P=0.245). In subjects wi th the G20210A mutation there was also no significant correlation between p rothrombin activity and concentration (n=6, r=0.200. P=0.704). Analyzing da ta from healthy blood donors without the prothrombin G20210A mutation (n=18 5), we found only weak correlations between prothrombin activity and concen tration of immunoreactive prothrombin (r=0.287; p<0.001). Samples with a re latively high prothrombin concentration but low activity were observed as w ell as samples with a relatively high activity for a given concentration (h yperactive prothrombin). F1+2 concentrations as indicators of activated coa gulation were only elevated in 13 of 125 investigated samples and could not explain any of these findings. Dysfunctional variants of prothrombin, a we ll known phenomenon, may be responsible for the former, and we speculate th at posttranscriptionally modified prothrombin species may explain the obser ved functional diversity of this factor including hyperactivity. The genoty pe-phenotype association of the non-coding G20210A mutation is not clear cu t. Therefore, further studies are needed to determine which factors apart f i-om the known G20210A poly morphism regulate prothrombin concentration and /or activity and may trigger the manifestation of thrombosis. (C) 2000 Else vier Science Ltd. All rights reserved.