Impact of the fibrinolytic enzyme system on prognosis and survival associated with non-small cell lung carcinoma

Abstract

Comprehensive studies of fibrinolysis in non-small cell lung carcinoma have been limited, and assignment of patients to high/low prognosis groups based on arbitrary cut-offs utilizing fibrinolytic measurements is unstandardized. This study was performed in 166 patients to examine the effects of cut-off values determined in three ways. Model 1 assigned patients to one of three equal groups (low, medium, high) based on fibrinolytic measurements made at diagnosis, Model 2 divided patients into low/high groups using median values, and Model 3 grouped according to the parameter being above/below normal range. In model 1, raised plasma fibrinogen, D-dimer and soluble fibrin were positively associated with poorer survival. In model 2, tissue plasminogen activator antigen was additionally related to poorer prognosis. Model 3 identified seven parameters as significantly related to survival, two not identified by the other models becoming significant [plasmin-antiplasmin, tissue plasminogen activator inhibitor-1 (PAI-1) antigen]. Using multivariate analysis, plasma fibrinogen level was the most uniformly significant parameter. Relative risk estimates indicated that raised plasma fibrinogen, soluble fibrin and D-dimer were associated with increased risk of death. Use of the normal/above normal cut-off is recommended to provide the maximum number of significant parameters relating to prognosis, and increased plasma D-dimer, PAI-1 antigen and fibrinogen were most closely related to survival/prognosis.

Plasma levels of D‐dimer in lung carcinoma

“…We focused on DD, a unique marker of coagulation and fibrinolytic activation. Our previous experience 16,17 and other studies 12,15,39 indicated that DD was the most useful variable. The weakness of the current study is that it does not provide any completely new evidence (approximately 7 of the 10 years encompassed by the current report, and 629 of 826 patients [76%] were included in the 2 previous publications).…”

“…32 As in many other human malignancies, [33][34][35][36][37][38] including lung carcinoma, DD might have prognostic significance. 12,15,39 In 1993, Seitz et al 12 reported that TAT and DD were significantly increased in patients with metastatic disease and that elevated TAT values at diagnosis might be prognostically significant. Taguchi et al 15 measured the plasma levels of DD in 70 lung carcinoma patients.…”

“…They found that low values of DD were significantly predictive of both good prognosis and longer survival times. Pavey et al 39 studied fibrinolytic markers in 166 lung carcinoma patients. Their principal aim was to evaluate the effects of cutoff values determined in three ways.…”

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

“…In cancer patients, several studies have reported high plasma concentrations of procoagulant proteins and decreased concentrations of functionally attenuated anti-coagulant factors [23][24][25]. Low fibrinolytic function has been also reported to be an important cause of vascular thrombosis in cancer patients [17]. So far, increased circulating level of PAI-1 has been ascribed as the main causative factor of hypofibrinolysis in patients with malignancy including those with lung cancer.…”

“…Tumor cells themselves may be the source of PAI-1 and PAI-2 [14,16]. The association of poor prognosis with circulating and tumor PAI-1 levels in patients with lung cancer illustrates the clinical relevance of fibrinolytic inhibitors in malignancy [17].…”