Elsevier

Thrombosis Research

Volume 99, Issue 2, 15 July 2000, Pages 111-117
Thrombosis Research

Original article
Relevance of Tissue Factor and Tissue Factor Pathway Inhibitor for Hypercoagulable State in the Lungs of Patients with Idiopathic Pulmonary Fibrosis

https://doi.org/10.1016/S0049-3848(00)00237-1Get rights and content

Abstract

We investigated the role of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Bronchoalveolar lavage (BAL) fluid was obtained from 22 patients with IPF, and the levels of TF and TFPI antigen were measured by ELISA. The TF and TFPI levels in BAL fluid supernatant were significantly higher in IPF patients than in normal controls. In addition, both levels were significantly higher in advanced cases than in nonadvanced cases. There was a significant correlation between the TF and TFPI levels Rs=0.541, p<0.05. Localization of TF and TFPI antigens was investigated by immunohistochemical staining. Both antigens were mainly localized in hyperplastic cuboidal epithelial cells, suggesting that the widespread distribution of these cells contributed to the increase of TF and TFPI antigen levels in the lungs of IPF patients. To assess whether TF activity is counterbalanced by TFPI in the lungs of IPF patients, we examined procoagulant activity and TF activity. It was found, however, that both procoagulant and TF activities were significantly higher in the BAL fluid supernatant of IPF patients than in that of normal controls, which suggested that TFPI was actually increased, but the increase was insufficient to counterbalance TF, leading to the development of a hypercoagulable state in the lungs of IPF patients.

Section snippets

Patients

A total of 22 patients with IPF were included in this study after giving their informed consent. All patients exhibited findings commonly seen in IPF, and usual interstitial pneumonia (UIP) findings were confirmed by either video-thoracoscopic or open-lung biopsy.

The clinical and laboratory findings of the patients are summarized in Table 1. Patients were divided into two groups according to the severity of pulmonary impairment: Patients with respiratory failure [PaO2 level less than 55 torr

TF and TFPI Antigen Levels in BAL Fluid Supernatant

Both TFPI and TF antigen levels were significantly higher in IPF patients than in controls. In addition, both TF and TFPI antigen levels were significantly higher in “advanced” patients than in “nonadvanced” patients (Table 2).

Regression analysis revealed a significant positive correlation between the TF and TFPI antigen levels in IPF patients (Figure 1).

PC Activity and TF Activity in BAL Fluid Supernatant

Both PC activity and TF activity were significantly higher in IPF patients than in normal controls (Table 2). However, there was no

Discussion

Our study showed that both TF and TFPI antigens were mainly positive in hyperplastic cuboidal alveolar epithelial cells in the lungs of IPF patients. The distribution of TF was quite consistent with previous observations by Imokawa et al. [4]. Regarding TFPI, the present study is the first report showing its localization in alveolar epithelial cells. Previous studies have indicated that TFPI is exclusively expressed in endothelial cells under physiologic conditions [10], and limited information

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