ELEVATED LEVELS OF PROTHROMBIN ACTIVATION FRAGMENT-1-V GENE (APC-RESISTANCE) AND(2 IN PLASMA FROM PATIENTS WITH HETEROZYGOUS ARG(506) TO GLN MUTATION IN THE FACTOR)OR INHERITED PROTEIN-S DEFICIENCY/

Inherited resistance to activated protein C (APC-resistance), caused b y a point mutation in the factor V gene leading to replacement of Arg( R)(506) with a Gin (Q), and inherited protein S deficiency are associa ted with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. , APC-resistance is often an additional genetic risk factor in thrombo sis-prone protein S deficient families. The plasma concentration of pr othrombin fragment 1+2 (F-1+2), which is a marker of hypercoagulable s tates, was measured in 205 members of 34 thrombosis-prone families har bouring the Arg(506) to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F-1+2 was significa ntly higher both in 38 individuals carrying the FV:Q(506) mutation in heterozygous stare (1.7 +/- 0.7 nM; mean +/- SD) and in 48 protein S d eficient cases (1.9 +/- 0.9 nM), than in 100 unaffected relatives (1.3 +/- 0.5 nM). Warfarin therapy decreased the F-1+2 levels, even in tho se four patients who had combined defects (0.5 +/- 0.3 nM). Our result s agree with the hypothesis that individuals with APC-resistance or pr otein S deficiency have an imbalance between pro- and anti-coagulant f orces leading to increased thrombin generation and a hypercoagulable s tate.