Diagnostic and prognostic values of plasma levels of fibrinolytic markers in ovarian cancer

OBJECTIVE: The aim of this study was to find out whether any of the fibrinolytic parameters could be used as tumor markers in predicting the prognosis of ovarian cancers. MATERIALS AND METHODS: In the present study, we determined the plasma concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), PAI-2, and uPA receptor (uPAR) in 25 patients with ovarian cancer, 16 patients with benign gynecologic tumor or inflammation, and 36 healthy controls in order to find out whether the plasma levels of these markers could be used to evaluate the prognostic value in patients with gynecologic cancers. We also determined two tissue concentrations of malignant tumor (one was at the tumor site itself and the other at the cut-end tissue of the tumor, which was expected to be free of tumor) in order to see the correlation between plasma and tissue concentrations. RESULTS: Plasma PAI-1 was significantly higher in patients with malignancy than in the healthy controls (P = 0.0001). There was no significant correlation between plasma and tissue concentrations, either tumor tissue or cut-end tissue, of the same parameters. Tissue concentrations of uPA, PAI-1, and PAI-2 were significantly higher and tPA significantly lower in the malignant tumor tissue than in the cut-end tissue in the patients with ovarian cancer (P = 0.014, 0.03, 0.002, and 0.01, respectively). Plasma PAI-1 was significantly higher in patients in the late stage of ovarian cancer than in the early stages and in the controls. CONCLUSION: From our study, we concluded that plasma levels of PAI-1 were correlated with the presence of malignant ovarian cancer and higher stage of disease.     

The lack of influence of normobaric oxygen on the generalized Shwartzman reaction in the rabbit

The influence of breathing oxygen on the generalized Shwartzman reaction in the rabbit was studied. We did not observe any effect of oxygen in the results of the ethanol gelation test, on the fibrinogen level in plasma nor on the fibrinolytic activity in euglobulins and in the renal cortex and outer medulla. The endotoxin-induced intraglomerular fibrin deposition was also unchanged in oxygen-breathing rabbits. It is concluded that the mechanism of the generalized Shwartzman reaction is unaffected by breathing normobaric oxygen.     

The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

Effect of bioresolving microspheric preparations of immobilized fibrinolysin on the fibrinolysis system

The effect of fibrinolysin, immobilized on microspherical carriers, on the fibrinolytic system of the blood was studied in dogs. A marked increase in fibrinolytic activity of whole blood was found at the site of deposition of the preparation on account of the enzyme introduced and increased activity of plasminogen activator. Administration of immobilized fibrinolysin leads to a more marked increase in activator activity than of plasmin activity. The results suggest the therapeutic value of this method of administration of the thrombolytic preparation.All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 16–18, January, 1980.     

Evaluation of some coagulation parameters in cerebral ischemia

ABSTRACT- In order to investigate some aspects of blood coagulation and of platelet function in cerebral ischemia, 18 healthy subjects, 24 patients with previous cerebral infarction and 12 patients with transient ischemic attacks were studied. All patients were in a non-active state of the illness. In all subjects, platelet count, prothrombin time, activated partial thromboplastin time and determination of the fibrinogen concentration were performed as routine. All subjects were tested for platelet adhesiveness, circulating platelet aggregates, factor VIII coagulant (VIII C), factor VIII-related von Willebrand factor (VIII RWF), factor VIII-related antigen (VIII RAg), antithrombin III (AT HI) concentration and activity and euglobulin clot lysis time. No significant difference between patients and controls was found in routine tests, platelet function, AT III concentration or activity. Plasma levels of VIII C, VIII RWF, VIII RAg were significantly increased in both patient groups. The VIII RAg/VIII C ratio was significantly increased only in patients with previous cerebral infarction. Euglobulin clot lysis time was significantly increased in both patient groups.     

Influence of detergents on the measurement of the fibrinolytic activity of plasminogen activators

The influence of detergents on the apparent activity of tissue plasminogen activator and of urokinase was investigated. The nonionic detergents Tween 80 and Triton X-100 and the zwitterionic detergent Zwitter-gent 314 caused a marked increase in the apparent activity of tissue plasminogen activator and, to a lesser degree, of urokinase in the fibrin plate assay, particularly at higher activator concentrations. These detergents did not enhance the plasma clot lysis in the presence of urokinase or tissue plasminogen activator. The anionic detergent sodium dodecyl sulfate had a small inhibitory action on the fibrin plate activity of urokinase and strongly inhibited the fibrin plate activity of tissue plasminogen activator. A systematic study into the mechanism of the stimulatory action of nonionic and zwitter-ionic detergents is presented.     

Pulmonary net release of tissue-type plasminogen activator during porcine primary and secondary acute lung injury

BACKGROUND: Tissue-type plasminogen activator (tPA) is a key mediator of fibrinolysis. Matching of pulmonary perfusion and ventilation is a critical denominator of oxygenation in acute lung injury (ALI). This study investigates pulmonary venoarterial plasma tPA gradients in association with acute ALI induced by bronchoalveolar lavage (BAL) and endotoxinemia (ETX). METHODS: Twenty-one anaesthetized, ventilated pigs were allocated to control (CTRL, n=5), bronchoalveolar saline lavage (BAL, n=8) or infusion of Escherichia coli endotoxin (ETX, n=8). Total tPA was analyzed in plasma (ELISA calibrated for porcine tPA). The inflammatory response was assessed by TNFa levels (ELISA). All variables were assessed at baseline and 2 h following ALI. RESULTS: Bronchoalveolar lavage and ETX induced similar increases in pulmonary shunt whereas pulmonary vascular resistance was significantly more increased in ETX animals. Cardiac output remained stable in BAL animals but decreased in ETX animals. The pulmonary venoarterial tPA plasma gradient increased in ETX animals, yielding a positive pulmonary net flux of tPA, which was absent in BAL animals. TNFalpha levels increased in ETX, but not in BAL, animals. A significant correlation was observed between TNFalpha and tPA plasma levels in ETX animals. All variables remained unchanged in CTRL animals. CONCLUSION: Plasma changes of tPA levels support a pulmonary release of tPA in early experimental ALI induced by acute ETX but not lavage, and are related to the inflammatory response. Despite increased vascular fibrinolytic capacity in ETX animals, pulmonary dysfunction was not different from BAL animals. The results demonstrate the close relation between inflammation and coagulation in early ALI.     

Serial changes in fibrinolysis and coagulation activation markers in acute and convalescent phase of ischemic stroke

BACKGROUND: The changes in the activity of a number of plasma markers of coagulation and fibrinolysis have previously been studied in patients with ischemic stroke, with conflicting results. We aimed to find out the changes in the activities of a wide array of markers of the coagulation and the fibrinolytic system of mildly or moderately affected first-ever ischemic stroke patients. METHODS: In a prospective, longitudinal, case-control study, we studied plasma plasminogen activator inhibitor type-1 (PAI-1) activity, tissue-type plasminogen activator antigen (t-PA:Ag), d-dimer, prothrombin fragment 1+2 (F 1+2), and thrombin-antithrombin III complex (TAT) levels in 55 consecutive patients on admission, 1 week, 1 month, and 3 months after an ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: PAI-1 activity was increased in the acute phase and at 3 months, D-dimer levels were significantly higher at 1 week and 1 month after stroke, whereas t-PA:Ag, TAT and F 1+2 levels remained stable during the whole study period. CONCLUSIONS: The changes of the fibrinolytic and coagulation system activity in the patients with mild or moderate ischemic stroke appeared minor compared with the results of previous studies, which included more severely ill patients.     

Tissue plasminogen activator for the treatment of intraabdominal abscesses in a neonate

Fibrinolytic agents have been used successfully in the management of loculated empyema; however, their use in the treatment of intraabdominal abscesses is limited. The authors describe the case of a 4-week-old girl with intraabdominal abscesses secondary to intestinal perforation that were not amenable to percutaneous drainage, but were managed successfully with intracavitary administration of tissue-plasminogen activator. This case represents the first report in a human, in which tissue-plaminogen activator was used to facilitate percutaneous drainage of an intraabdominal abscess. It is also the first time a fibrinolytic agent has been used for this purpose in a child.