Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples

Abstract

Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.

Gene targeting in hemostasis. tissue factor pathway inhibitor

“…Not surprisingly, TFPI plasma concentrations correlate directly with plasma LDL levels, such that levels are increased in diet-induced hypercholesterolemia , and decreased in those with abetalipoproteinemia (11). These latter patients however demonstrate no tendency for thrombosis.…”

Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients

“…It has two major isoforms: TFPI-ß is an active, truncated form anchored to the endothelial surface via a glycosylphosphatidylinositol moiety; TFPI-a is an active, full-length form found in plasma. In addition, a large reservoir of TFPI-a (two to four times the plasma concentration (14,15)) is noncovalently bound to endothelial cell heparan sulfate proteoglycans such as SDC-1. Platelets also contain TFPIa, with the platelet-associated pool amounting to $10% of the total plasma pool.…”