ABSTRACT
The protease inhibitor, tissue factor pathway inhibitor (TFPI), is an endogenous Kunitz-type
inhibitor of the tissue factor (TF)-mediated coagulation pathway that plays an important role in
hemostasis. TFPI exerts its action by first binding to factor Xa (FXa) and forming a TFPI-FXa
complex, which then, in a second step, binds and effectively inhibits the tissue factor (TF)–factor
VIIa (FVIIa) complex. Both full-length TFPI and chemically modified forms (e.g., truncated,
glycosylated, or phosphorylated TFPI variants) exert various pharmacological effects. The
anticoagulant and antiplatelet actions of TFPI, its potency in inhibiting thrombin and factor
Xa generation, as well as its antithrombotic effect shown in different animal models of venous
and arterial thrombosis make this inhibitor a promising agent that could be potentially useful for
several clinical indications. The inhibitory action of TFPI is accelerated by both heparins and
other glycosaminoglycans that are capable of releasing TFPI from the vascular endothelium,
which contributes to the antithrombotic effectiveness of these drugs. The clinical relevance of
TFPI continues to be explored. From the beneficial actions in animal studies and on the results
obtained in the first clinical investigations, TFPI is expected to be effective in the treatment of
various diseases, such as disseminated intravascular coagulation (DIC), sepsis, coronary
syndromes, stroke, and acute respiratory distress syndrome (ARDS). Further clinical trials
designed to clarify the role of TFPI and especially its potential usefulness as a prophylactic or
therapeutic agent are ongoing.
