fibrinopeptide-b and Thromboembolism

The mutual relationships between malignant tumours and mechanisms of blood coagulation are presented in a brief survey. In this connection, the mechanisms of a tumour cell entering the circulation through the vessel well and its leaving into the tissues are discussed, the theory of microtrauma being used for explaining these processes. Subsequently, the alterations to be found in the count and function of thrombocytes after contact with a malignant cell and the impact on this cell by blood platelets are represented. As a third factor the activation of blood coagulation which is exercised by substances with a procoagulatory effect produced by the malignant tissue and the frequently observed thrombosis in the course of neoplastic diseases are dealt with in connection with blood level changes of some coagulation factors. In a fourth section the significance of fibrinolysis, its activation and inhibition as well as the production of fibrinolytic activators by neoplasms are discussed.

Topics: Animals; Blood Coagulation Factors; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Neoplasms; Neoplastic Cells, Circulating; Plasminogen Activators; Platelet Aggregation; Thromboembolism

The role of active thrombosis in the pathophysiology of pulmonary embolism is unclear. We tested the hypothesis that venous thrombi significantly increase their thrombotic activity once they embolize into the high-flow circulation of the pulmonary arteries. Thrombotic activity was measured using an immunoassay that measures both fibrinopeptide B (FPB) as well as its most abundant metabolite des-arginine FPB. Thrombi were formed in the femoral veins of adult dogs. In one group, the thrombi were embolized without anticoagulation. In the second group, heparin (300 U/kg bolus, then 90 U x kg(-1) x h(-1) infusion) was administered before embolization to prevent subsequent thrombotic activity. Plasma FPB concentrations were significantly suppressed in the heparinized group relative to the nonheparinized group for 1 h postembolization (P = 0.038). We conclude that pulmonary embolization itself causes preexisting venous thrombi to greatly intensify their thrombotic activity and that embolization-associated thrombus propagation can be prevented by heparin.

Topics: Ancrod; Animals; Anticoagulants; Dogs; Fibrinogen; Fibrinopeptide B; Heparin; Humans; Male; Pulmonary Embolism; Thromboembolism; Thrombosis

In five patients with venous thromboembolic disease treated with recombinant tissue-type plasminogen activator (rt-PA), there was a marked increase in the mean concentrations of fibrinopeptide A (from 0.6 to 5.9 nM; P less than 0.0001) and desarginine fibrinopeptide B (from 5.6 nM to 24.1 nM; P less than 0.01) 30 min after a bolus of rt-PA (0.6 mg/kg). Thrombin was unlikely to be responsible because the levels of desarginine fibrinopeptide B exceeded those of fibrinopeptide A and the changes occurred despite concomitant heparin therapy. The purpose of this study therefore, was to determine whether rt-PA directly releases the fibrinopeptides from fibrinogen. Incubation of rt-PA with heparinized plasma or purified fibrinogen resulted in time and dose-dependent release of both fibrinopeptide A and B. Contaminating thrombin was not responsible for this activity by the following criteria: the rate of rt-PA mediated fibrinopeptide B release was considerably faster than that of fibrinopeptide A, and fibrinopeptide release was unaffected by heparin, hirudin, or a monospecific antithrombin IgG. Aprotinin also had no effect on fibrinopeptide release, indicating that this activity was not plasmin mediated. Fibrinopeptide release was shown to be due to rt-PA because this activity was completely blocked by a monoclonal antibody against the enzyme. Further, the specificity of rt-PA for the thrombin cleavage sites on fibrinogen was confirmed by the demonstration that rt-PA released fibrinopeptide A or fibrinopeptide B from fibrinopeptide A or B-containing substrates, respectively. These studies thus demonstrate that (a) rt-PA releases fibrinopeptides A and B from fibrinogen thereby indicating that this enzyme is not specific for plasminogen, and (b) plasma fibrinopeptide A and desarginine fibrinopeptide B levels are not specific markers of thrombin action on fibrinogen in patients receiving rt-PA.

Topics: Chromatography, High Pressure Liquid; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Heparin; Humans; Recombinant Proteins; Thrombin; Thromboembolism; Tissue Plasminogen Activator

Topics: Adolescent; Adult; Aged; beta-Thromboglobulin; Female; Fibrinopeptide A; Fibrinopeptide B; Humans; Leg; Lung; Male; Middle Aged; Platelet Factor 4; Postoperative Complications; Radionuclide Imaging; Thrombin; Thromboembolism; Thrombophlebitis; Thromboplastin

Topics: Animals; Anticoagulants; Disseminated Intravascular Coagulation; Dogs; Epitopes; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Heparin; Humans; Radioimmunoassay; Thrombin; Thromboembolism; Thrombosis