Tomoya Yamakami

Coagulation-Fibrinolysis System and Markers of Collagen Metabolism in Lung Cancer

Background. Evidence suggests that the fibrinolysis system and peritumoral connective tissue play important roles in tumor spread.

Alteration of Coagulation and Fibrinolysis Systems After Multidrug Anticancer Therapy for Lung Cancer

Recently, an increased frequency of thromboembolic events has been reported after the administration of anticancer drugs. The precise mechanism by which these vascular phenomena occur is unknown. The current work aims at evaluating the alterations of the coagulation and the fibrinolysis systems during the administration of antineoplastic agents by means of newly developed markers of haemostasis. This investigation comprised 25 lung cancer patients treated with multidrug combination chemotherapy. D-dimer, plasmin-alpha 2-antiplasmin complex, fibrin degradation products, fibrinogen, antithrombin III, thrombin-antithrombin III complex, prothrombin time and activated partial thromboplastin time were measured from samples taken before and on days 2, 5, 7, 14 and 21 after the administration of antineoplastic drugs. A significant reduction in plasma concentration of fibrinolytic activity markers, DD and PAP, was observed on days 5 and 7, and on days 2, 5, 7 and 14, respectively, following the administration of chemotherapeutic drugs. Statistically significant shortening of PT and APTT on days 2, 5, 7 and 14, as well as significant elevation of the thrombin generation marker TAT were observed on days 5 and 7 after chemotherapy. These results show that relatively higher levels of coagulation activation and a lower fibrinolytic activity occur during cytotoxic drug therapy compared with basal values. Small variations of haemostatic values and a short follow-up period may explain why no thrombotic events were observed during this study. Although further studies must be done to clarify these findings, the results of this investigation suggest that an imbalance of the coagulation-fibrinolysis system might be a contributing factor in the pathogenesis of thrombotic complications during chemotherapy.

High plasma level of plasmin-α2-plasmin inhibitor complex is predictor of poor prognosis in patients with lung cancer

The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.

Correlation between increased granulocyte elastase release and activation of blood coagulation in patients with lung cancer

Background. Coagulopathies often are associated with malignant tumors. The pathogenesis of these complications in cancer is not clear. Host inflammatory (monocyte/macrophage) cell‐mediated triggering of clotting activation has been suggested.