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Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an immune-mediated mechanism. However, abnormalities of the clotting system have also been incriminated as having an important role in the pathogenesis of this disease. This study aims at assessing the clotting system and collagen metabolism alterations and the relationship between perturbances of the hemostatic pathway and the destructive and fibroproliferative processes in patients with rheumatoid arthritis. The coagulation system was evaluated by measuring thrombin-antithrombin III complex (TAT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis system was assessed by measuring fibrin degradation products (FDP), fibrinogen (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2-antiplasmin complex (PAP). As markers of collagen metabolism, the type III procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen) were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen were significantly higher in rheumatoid arthritis patients compared to controls. Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP, and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This study demonstrated the occurrence of a subclinical intravascular coagulation in rheumatoid arthritis and suggested the important role of blood coagulation in the alteration of the extracellular matrix metabolism in this disease.

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., Methods: The objective of this study was to evaluate the role of neutrophil-derived elastase in the activation of blood coagulation and fibrinolysis in lung cancer. The study population was 42 consecutive patients with lung cancer (34 men and 8 women). Thirteen patients had small cell lung cancer (SCLC), 13 had squamous cell lung cancer, and 16 had adenocarcinoma. Hemostatic function was assessed by measuring D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-antiplasmin complex (PAP), fibrin degradation product (FDP), fibrinogen, prothrombin time (PT) and activated partial thromboplastin time (APTT). Elastase-alpha 1-protease inhibitor (EPI) complex was measured as a marker of neutrophil activation., Results: Significant elevation of the elastase plasma levels and coagulation-fibrinolysis parameters was found in patients with cancer compared with control subjects. Among all patients, the plasma concentration of EPI was significantly correlated with APTT, DD, TAT, PAP, and fibrinogen. Although in patients with non-small cell lung cancer (non-SCLC), DD, TAT, PAP, APTT, and fibrinogen were significantly correlated with EPI, such a correlation was not found in patients with SCLC. Patients with non-SCLC had stronger correlation of EPI with TAT, PAP, and PT than did patients with advanced stages of disease., Conclusion: The activation of coagulation-fibrinolysis system in lung cancer may be triggered, at least in part, by an increased release of neutrophil elastase. This mechanism is stage related and seems to operate predominantly in non-SCLC.

Clotting abnormalities are well-recognized complications that occur with high frequency in patients suffering from underlying malignant diseases. New and highly sensitive molecular markers of hemostasis, thrombin-antithrombin III complex (TAT III), D-dimer fragments (DD), and plasmin-alpha 2-antiplasmin complex (PIC) were measured in 58 consecutive lung cancer patients. Significant elevation in the blood concentrations of DD, PIC, and TAT was found in lung cancer patients, with either extensive or limited disease compared with values obtained in a healthy control group and in another group of patients with chronic obstructive pulmonary disease. Patients with distant metastasis exhibited significantly higher levels of these parameters as compared to those without metastasis. These data indicated that there was a subclinical activation of blood coagulation and fibrinolysis in lung cancer from the early clinical stages of the disease. In addition, there appeared to be different levels of clotting activation according to histologic type of tumor and response to chemotherapy.