Summary
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.
Thrombinantithrombin complex (TAT) was significantly increased in MI patients (8.2
± 12.9 µg/l vs. 3.9 ± 2.6 µg/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.
Keywords
Tissue factor pathway inhibitor (TFPI) - tissue factor / factor VII - ischaemic heart
disease - thrombin