Rühl H, Berens C, Winterhagen FI, et al. - In view of the recent work indicating that the FVL (factor V Leiden) mutation accelerates thrombin and APC (activated protein C) formation in carriers without a history of venous thromboembolism (VTE), researchers examined if a similar reaction pattern is induced by the FII (prothrombin) 20210G>A mutation, and if FVL and FII 20210G>A mutation carriers with prior VTE (VTE+) differ in the response rates. They infused recombinant factor VIIa (15 µg/kg) in 30 FVL carriers, 28 FII 20210G>A carriers (thereof 13 VTE+ each) and 15 healthy controls and then monitored them for changes in plasma levels of thrombin, prothrombin activation fragment 1+2 (F1+2), TAT (thrombin-antithrombin complex), APC, and D-dimer over 8 hours. FVL and FII 20210G>A carriers showed a similar increase of F1+2 and TAT levels, asymptomatic and VTE+ carriers of these mutations were also similar regarding the increase of F1+2 and TAT levels. A higher increase in median plasma levels of APC was observed among FVL carriers that FII 20210G>A carriers and among FII 20210G>A carriers than healthy controls. Most importantly, asymptomatic (n = 13) vs VTE+ (n = 12) heterozygous FVL carriers had greater APC response. These findings suggest that in vivo coagulation activation leads to higher APC formation rates among carriers of the FII 20210G>A mutation and of the FVL mutation than healthy individuals. Among the FVL carriers, there appeared a correlation of APC response rates with the thrombotic risk as individuals with a history of unprovoked VTE showed significant lower APC levels than those without thrombosis.