INTRODUCTION: The protein C anticoagulant system is of major importance in the regulation of thrombotic risk, but it is not known whether low plasma levels of activated protein C (APC) in vivo reflect a compromised anticoagulant situation with increased thrombotic risk. Previous studies have reported low, normal or increased plasma APC levels in unselected patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We performed a population-based, case-control study in patients with a previous history of unprovoked VTE and subjected the participants to a standard fat tolerance test (1g fat/kg body weight) in order to promote physiological coagulation activation. RESULTS: VTE patients had higher BMI (28.3 ± 4.4 kg/m(2) versus 26.3 ± 3.9 kg/m(2), p=0.045) and greater waist circumference (98.2 ± 12.5 cm versus 93.4 ± 13.4 cm, p=0.041) than age and sex matched controls. APC levels were equal in fasting plasma (3.00 ± 0.74 ng/ml and 2.99 ± 0.60 ng/ml, p=0.66) but higher in postprandial plasma (3.18 ± 0.57 ng/ml and 2.81 ± 0.38 ng/ml, p=0.008) collected from VTE patients and controls, respectively. Endogenous thrombin generation in plasma following a standardized meal, assessed by thrombin-antithrombin complex (TAT), increased similarly in both groups, whereas APC increased only among the VTE patients during the postprandial state. Plasma levels of APC increased linearly with TAT in the postprandial state (p for linear trend=0.012). CONCLUSIONS: Our findings fail to support the hypothesis that low APC levels are linked to increased thrombotic risk in unprovoked VTE, and they suggest that plasma APC is a biomarker of thrombin generation. Copyright
INTRODUCTION: The protein C anticoagulant system is of major importance in the regulation of thrombotic risk, but it is not known whether low plasma levels of activated protein C (APC) in vivo reflect a compromised anticoagulant situation with increased thrombotic risk. Previous studies have reported low, normal or increased plasma APC levels in unselected patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We performed a population-based, case-control study in patients with a previous history of unprovoked VTE and subjected the participants to a standard fat tolerance test (1g fat/kg body weight) in order to promote physiological coagulation activation. RESULTS:VTEpatients had higher BMI (28.3 ± 4.4 kg/m(2) versus 26.3 ± 3.9 kg/m(2), p=0.045) and greater waist circumference (98.2 ± 12.5 cm versus 93.4 ± 13.4 cm, p=0.041) than age and sex matched controls. APC levels were equal in fasting plasma (3.00 ± 0.74 ng/ml and 2.99 ± 0.60 ng/ml, p=0.66) but higher in postprandial plasma (3.18 ± 0.57 ng/ml and 2.81 ± 0.38 ng/ml, p=0.008) collected from VTEpatients and controls, respectively. Endogenous thrombin generation in plasma following a standardized meal, assessed by thrombin-antithrombin complex (TAT), increased similarly in both groups, whereas APC increased only among the VTEpatients during the postprandial state. Plasma levels of APC increased linearly with TAT in the postprandial state (p for linear trend=0.012). CONCLUSIONS: Our findings fail to support the hypothesis that low APC levels are linked to increased thrombotic risk in unprovoked VTE, and they suggest that plasma APC is a biomarker of thrombin generation. Copyright
Authors: C T Esmon; W Ding; K Yasuhiro; J M Gu; G Ferrell; L M Regan; D J Stearns-Kurosawa; S Kurosawa; T Mather; Z Laszik; N L Esmon Journal: Thromb Haemost Date: 1997-07 Impact factor: 5.249
Authors: R M Bertina; B P Koeleman; T Koster; F R Rosendaal; R J Dirven; H de Ronde; P A van der Velden; P H Reitsma Journal: Nature Date: 1994-05-05 Impact factor: 49.962
Authors: M Cattaneo; F Franchi; M L Zighetti; I Martinelli; D Asti; P M Mannucci Journal: Arterioscler Thromb Vasc Biol Date: 1998-09 Impact factor: 8.311
Authors: K Minamikawa; H Wada; Y Wakita; M Ohiwa; M Tanigawa; K Deguchi; N Hiraoka; H Huzioka; J Nishioka; T Hayashi Journal: Thromb Haemost Date: 1994-02 Impact factor: 5.249