State and diagnostic value of plasma tissue factor in early‐hospitalised patients with chest pain

Abstract

SummaryTo study the state and diagnostic value of plasma tissue factor (TF) in patients with acute coronary syndromes (ACS), we quantitatively compared plasma TF antigen and TF activity in 90 early-hospitalised patients with chest pain. Using high-affinity antibodies, a sensitive assay for TF antigen was developed with a detection limit of 40 fmol/l. One of the antibodies was used to capture TF from plasma and, after elution and dialysis-free reconstitution in phospholipid-glucoside micelles, absolute amounts of TF activity could be measured with a detection limit of 80 fmol/l. All TF in plasma was found to be exposed, and a value of 2AE5(1AE1-14AE8) pmol/l (median with range) was found for TF antigen. Most of this TF antigen (70-80%) circulated in a (potentially) functional state. Left in its in vivo state, however, TF captured from plasma was totally inactive, probably because of the lack of a procoagulant matrix. Compared with controls with non-cardiac chest pain, TF activity was unchanged and TF antigen about 25% elevated in ACS patients. Combined with the markers prothrombin fragment F1+2 and fatty acid-binding protein, TF did not improve the early diagnosis of ACS.

Tissue factor serum levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC‐Norfolk prospective population study

“…Circulating TF is a balance between excretion and immobilization of the molecule from activated monocytes, endothelial cells or subendothelial lineage from an inflamed site on a vessel. Although there is still an ongoing debate about the functional role of TF in the circulation [21,22], it has recently been shown that circulating TF is (potentially) active but inhibited in vivo [19]. In addition, our results suggest that high production on inflamed sites does not warrant high circulating levels.…”

“…Thirdly, in our study we measured TF antigen levels, whereas other studies have measured TF activity. In patients with acute coronary syndromes, antigen levels are 20-30% higher than activity levels, and correlation coefficients of approximately 0.5 between activity and antigen have been described [19]. Finally, TF activity is influenced by natural positive and negative feedback mechanisms, i.e.…”

“…Results were related to a standard consisting of commercially available CRP (Behringwerke AG, Marburg, Germany). Serum TF levels were measured with monoclonal antihuman TF antibodies from Sanquin Reagents (Amsterdam, The Netherlands), as recently described by van der Putten et al [19]. These authors showed that TF levels measured with this ELISA are comparable between serum and plasma samples [20].…”

Plasma TF activity predicts cardiovascular mortality in patients with acute myocardial infarction

“…[ 28 ]. The increase in TF activity observed in the present study, might reflect a systemic hypercoagulable state [ 29 , 30 ]. There is growing evidence that circulating TF is potentially active in an encrypted state, where it can bind FVII, but lacks proteolytic activity [ 31 ].…”

Factor XIa and tissue factor activity in patients with coronary artery disease

“…As aconsequence of elevatedprocoagulant activity,higher levels of coagulation markers such as prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT ), fibrinopeptide A, the D-dimer,soluble fibrinogen, etc.are observed (7)(8)(9)(10). Although therea re studiess uggesting elevatedc oncentrations of soluble TF in plasma of CAD patients, the prognosticvalue of TF assays remains controversial (11)(12)(13). Forexample, Campo et al suggested that plasma TF levelisapredictor of mortality in patients with acute MI (13),while other authorsreport no significant differences in TF activity (12)orantigen (11) betweenACS patients and stable controls.…”