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Introduction: Tissue factor (TF)-induced thrombin generation (TG) ex vivo has been suggested to be an important method to assess thrombotic risk. No studies have investigated the impact of postprandial lipemia on TF-induced TG. Since myocardial infarction (MI) is associated with elevated postprandial levels of triglycerides, we hypothesized a differential impact of postprandial lipemia on coagulation activation in MI-patients and healthy controls., Material and Methods: Elderly survivors of acute MI (n=44) and healthy age-and sex matched controls (n=43) underwent a fat tolerance test (1 gram per kg body weight) to assess coagulation activation during postprandial lipemia., Results: The incremental area under the curve (AUCi) for serum triglycerides was higher in MI-patients than in healthy age-and sex matched controls (5.64±0.52 mmol/L*h and 3.94±0.39 mmol/L*h, p=0.012) during the postprandial phase. Subsequent endogenous activation of coagulation, assessed by FVIIa and thrombin generation (F1+2), was similar among groups and not related to levels of triglycerides during the postprandial phase. Healthy individuals had a gradual decline in TF-induced thrombin generation ex vivo, assessed by endogenous thrombin potential (ETP) (AUCi=-542.4±71.4 nM*min*h, p<0.001), whereas MI-patients retained their ETP (AUCi=127.4±89.0 nM*min*h, p=0.47) in plasma during the postprandial phase (p for group difference=0.005)., Conclusions: MI-patients had elevated postprandial lipemia and retained their ability for TF-induced TG in plasma ex vivo in the postprandial phase, whereas the capacity gradually decreased in healthy individuals. Further studies are warranted to reveal underlying mechanism(s) and clinical implications., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Formation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-FVIIa complexes on ruptured atherosclerotic plaques is thought to be a key event in acute MI. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation by neutralizing FXa and inhibiting the TF-FVIIa complex. A case control study was conducted to investigate the role of coagulation activation in MI. Sixty-two patients with verified MI, 40-60 yrs of age, were recruited into the study and examined 1-4 years after the acute coronary event. Thrombin-antithrombin complex (TAT) was significantly increased in MI patients (8.2 +/- 12.9 microg/l vs. 3.9 +/- 2.6 microg/l, p=0.01). In contrast, FVIIa was lower in MI patients (41 +/- 13 mU/ml vs. 48 +/- 15 mU/ml, p=0.003) accompanied by an increase in plasma free TFPI antigen (20.9 +/- 5.0 ng/ml vs. 19.2 +/- 4.9 ng/ml, p=0.03). Significant trends for increase in triglycerides and total cholesterol across quartiles of free TFPI Ag were found in both groups, whereas HDL cholesterol decreased across quartiles of TFPI among control subjects. The compensatory increase in plasma free TFPI with established lipid and haemostatic risk factors were abrogated in the MI patients. An apparent increase in the basal activation of the coagulation system was observed in young patients with MI. Enhanced coagulation activation was accompanied by a decrease in FVIIa and increase in free TFPI Ag, probably reflecting a modest triggering of TF-induced coagulation in these patients.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation, which is increased several-fold in post-heparin plasma and thought to contribute significantly to the antithrombotic action of heparin. In the present study we investigated whether subcutaneous (s.c.) administration of a low molecular weight heparin (LMWH), enoxaparin, had a different effect on intravascular pools of TFPI compared with continuous i.v. infusion of unfractionated heparin (UFH). 18 healthy male volunteers were randomly assigned to continuous i.v. infusion with UFH (initially 450 U/kg/24 h, n = 6) or to s.c. treatment with LMWH once daily (enoxaparin, 1.5 mg/kg, n = 12) for 72 h. A bolus injection of 5000 IU UFH i.v. caused an 8–13-fold increase in plasma-free TFPI antigen (TFPI Ag), followed by a progressive decrease (81 ± 4%, P < 0.001) during the 72 h infusion with UFH. 4 h after discontinuation of the infusion, basal free TFPI Ag and heparin-releasable TFPI were significantly decreased compared with the concentrations before the infusion (30 ± 9% and 27 ± 7%, respectively). In contrast, LMWH treatment did not reduce either basal or heparin-releasable TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statistically different between groups both in pre- (P < 0.001) and post-heparin (P < 0.0001) plasma. The differential effect of UFH and LMWH on intravascular pools of TFPI may contribute to the understanding of the apparent superior efficacy of LMWHs in the treatment of both arterial and venous thrombosis. [ABSTRACT FROM AUTHOR]