Heightened thrombin generation in individuals with resistance to activated protein C.
We chose to evaluate whether or not a state of biochemical hypercoagulability was present in 74 individuals (69 heterozygotes and 5 homozygotes) resistant to activated protein C (APC) due to the Arg506 --> Gln mutation in the factor V gene. To this end, plasma levels of two markers of thrombin formation, prothrombin fragment 1 + 2 (F1+2) and thrombin-antithrombin complexes (TAT) were measured. High levels of F1+2 and TAT were found in 32% and 23% of APC-resistant individuals vs 4% in controls. The levels of these markers tended to be particularly elevated in three homozygous subjects. A significant positive correlation between F1+2 and TAT was present in APC-resistant individuals. No relationship between marker values and the previous occurrence of thrombotic episodes was found. Therefore, by measuring F1+2 and TAT a state of biochemical hypercoagulability has been identified in about one-third of APC-resistant individuals. This frequency is similar to that previously observed in comparable individuals with inherited deficiencies of protein C and protein S, which are usually associated with a stronger thrombotic tendency than APC-resistant individuals.
Martinelli
I
I
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Italy.
Bottasso
B
B
Duca
F
F
Faioni
E
E
Mannucci
P M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D002648:Child; D004351:Drug Resistance / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D011486:Protein C / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000032:analysis* / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000209:etiology / Q000235:genetics
D000925:Anticoagulants; D011486:Protein C; D005165:Factor V; D011516:Prothrombin; D013917:Thrombin