ABSTRACT
Thrombosis at the site of atherosclerotic plaque disruption is the principal cause
of acute coronary syndromes. The severity of the clinical consequences is determined
by the extent and the progression of the thrombus that are caused by local and systemic
factors. In atherosclerotic lesions mediators induce tissue factor (TF) in macrophages,
smooth muscle cells, and endothelial cells. Procoagulant microparticles in the lipid
core further enhance the thrombogenicity of the plaque. In addition, in acute coronary
syndromes circulating monocytes and microparticles express TF and, thereby, contribute
to systemic procoagulant activity. As a regulatory mechanism surface-bound, endogenous
tissue factor pathway inhibitor-1 (TFPI) inhibits TF activity by translocation of
the quaternary complex TF-FVIIa-FXa-TFPI into glycosphingolipid-rich microdomains
more efficiently than exogenously added TFPI. This inhibition occurs not only in endothelial
cells but also on circulating monocytes and presumably microparticles. Because therapeutic
thrombolysis in acute myocardial infarction degrades TFPI, a prothrombotic state due
to unopposed TF activity may occur. Several studies have demonstrated a contribution
of local and bloodborne TF to thrombus formation; a direct relationship with the clinical
outcome, however, awaits further studies. This article discusses the current understanding
of the role of TF and its regulation by TFPI in acute coronary syndromes.
KEYWORDS
Tissue factor - acute coronary syndrome - coagulation - thrombolysis
