Abstract
The extrinsic pathway is probably the predominant pathway in initiating blood coagulation
in inflammatory lung diseases. Tissue factor pathway inhibitor (TFPI) is a Kunitz-type
protease inhibitor of factor VIIa/tissue factor in the presence of factor Xa. As it
has been shown recently that TFPI plasma levels are increased under acute inflammatory
conditions, we studied TFPI antigen plasma levels before and after injecting 20 IU/kg
body weight of unfractionated heparin into 49 patients with different stages of sarcoidosis,
into 9 with idiopathic pulmonary fibrosis, and into 15 normal controls.
TFPI, before injecting heparin, was significantly increased in all sarcoidosis stages
(stage I: 97.6 ± 6.4 ng/mL; stage II: 116.2 ± 11.9 ng/mL; stage III: 116.3 ±7.3 ng/mL)
and in idiopathic pulmonary fibrosis (116.8 ± 16.1 ng/mL), as compared to the control
group (77.7 ± 3.3 ng/mL). No correlation was found between the intensity of the activity
of sarcoidosis, measured as BAL white cell count, and TFPI. Five minutes after heparin
administration the rise in TFPI was lower, although not statistically significant,
in all sarcoidosis stages than in controls. In contrast, idiopathic pulmonary fibrosis
had a similar or even higher TFPI elevation than the control group.
In sarcoidosis the elevated TFPI and the lower capacity by endothelial cells to release
TFPI after heparin may represent a compensatory mechanism to prevent blood clotting
and/or the endothelial cell dysfunction of the microvasculature in this condition.
In contrast, the extensive mesenchymal cell proliferation present in idiopathic pulmonary
fibrosis could explain our findings, as it has been shown that cultured human mesangial
cells produce and release TFPI.
Keywords:
Tissue factor pathway inhibitor (TFPI) - sarcoidosis - idiopathic pulmonary fibrosis
- heparin - factor VIIa/tissue factor
