The rediscovery and isolation of TFPI

Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type proteinase inhibitor that produces factor (F)Xa-dependent feedback inhibition of the factor VIIa/tissue factor (FVIIa/TF) catalytic complex that is responsible for the initiation of coagulation. Since 1985, when Rapaport and colleagues reported that the lipoprotein fraction of plasma contained a FXa-dependent inhibitor of FVIIa/TF, myriad articles have established its biochemical structure, its mechanism of action, and its physiological importance. This brief personal account reviews historical studies that established the existence of the inhibitor and the events that led to its initial isolation.