Fibrinolysis Platelet Research Articles

Platelet-Mediated Modulation of Fibrinolysis.

Platelets are crucial to the hemostatic response. Their role in coagulation is well documented and they have been considered for some time to promote resistance of thrombi to fibrinolysis. Platelets confer resistance to lysis by promoting clot retraction of the immediate fibrin network and through release of plasminogen activator inhibitor-1 from their α-granules. However, recent developments in the field indicate that the role of platelets in fibrinolysis is much more diverse. Indeed, novel studies suggest that platelets form different subpopulations upon activation that play varied roles in regulating hemostasis. Likewise the developments in our understanding of thrombus formation, architecture, and changes in fibrin deposition and composition suggest that these different subpopulations of platelets may populate distinct areas within thrombi and potentially dictate the local hemostatic balance in these areas. This review will discuss the diverse roles of platelets in fibrinolysis and highlight the recent developments in the field and the contribution of both the intracellular pool of modulators as well as the membrane surface in regulating these processes.

Tissue Plasminogen Activator in Human Megakaryocytes and Platelets: Immunocytochemical Localization, Immunoblotting and Zymographic Analysis

Two approaches were used to identify and characterize the presence of tissue plasminogen activator (t-PA) in megakaryocytes and platelets. We investigated the fibrinolytic activity of human megakaryocytes (MK) and platelets. The presence of t-PA antigen in megakaryocytes and platelets was demonstrated using immunocytochemical techniques and polyclonal or monoclonal antibodies specific for t-PA. When cells were applied to fibrin plates, lysis zones developed around isolated human megakaryocytes, whereas no fibrinolytic activity appeared when either intact washed platelets or platelet lysate were deposited. After SDS-PAGE of platelet and MK extracts (Triton X-100) immunoblotting and peroxidase staining identified t-PA antigen in several bands. Zymographic analysis of SDS-PAGE carried out on fibrin film overlays identified one or two zones corresponding to free or complexed t-PA. These results indicate that t-PA is present in platelets as well as in the precursor cells, however, in platelets, t-PA may not be immediately available for plasminogen activation and fibrin degradation. From our findings and from previous work of others, it appears that platelets may either activate or inhibit the fibrinolytic system. Therefore the conditions of plasminogen activation by platelet t-PA and plasmin inhibition by platelet alpha 2-antiplasmin or other inhibitors have to be precised before the role of platelets in clot dissolution is understood. The physiological role of platelets in fibrinolysis and clot dissolution remains unclear. In 1953, the antifibrinolytic activity of blood platelets was demonstrated and in the early 1960's a fibrinolytic activity, increasing with platelet concentration in the experimental system, was shown.(ABSTRACT TRUNCATED AT 250 WORDS)

The potentiating effect of platelet on plasminogen activation by tissue plasminogen activator

A new role for platelets in fibrinolysis is proposed. Platelets (euglobulin from platelet rich plasma and from human platelet extract) may potentiate plasminogen activation by tissue plasminogen activator(tPA). The potentiating activity was detected by both chromogenic substrate and fibrin plate analysis. The fibrinolysispotentiating substance in the platelets required the presence of both tPA and plasminogen, suggesting that it potentiates the activation of plasminogen by tPA. This substance was not related to fibrinogen degradation products because it was also present in platelets from two afibrinogenemic patients and did not lose its activity when separated from fibrinogen-related antigen by Sepharose 2B gel filtration. Since platelets contain both activator(s) and inhibitor(s) of plasminogen activation by tPA, a balance between activator(s) and inhibitor(s) in platelets may also be required for control of the fibrinolytic pathway.

Inhibitors of fibrinolysis in platelets in polycythaemia vera and thrombocytosis.

Summary. The role of platelets in fibrinolysis was studied in relation to their content of fibrinolytic inhibitors. An antiplasmin was present in platelets when studied by the caseinolytic method, but this antiplasmin was weak when the fibrin plate method was used. Thus the fibrin plate method could be used for the study of the inhibitory action of platelets against three different types of plasminogen activator: urokinase, human heart tissue activator and human plasma plasminogen activator. It was found that normal human platelets contained inhibitors against all three plasminogen activators with the highest inhibitory activity against urokinase. Platelets from patients with thrombocytosis due to polycythaemia vera or secondary to bronchogenic carcinoma also showed similar inhibitory activity. The platelets from one patient with polycythaemia vera had an unusually high degree of inhibitory activity. The significance of these findings is discussed with respect to the relative resistance of a platelet thrombus to lysis and to its role in haemostasis.

The role of platelets in fibrinolysis: studies on the plasminogen activator and antiplasmin activity of platelets

Inhibition of plasmin and activation of plasminogen by platelet-poor plasma, intact, lysed and thrombin-aggregated platelet-rich plasma, and washed platelets was studied by means of fibrin-agar plates. No significant activation of plasminogen by platelets could be demonstrated. Maximal inhibition of plasmin occurred after 2-3hr. incubation with either platelet-rich or platelet-poor plasma; in each case the kinetics of the reaction were suggestive of non-competitive inhibition. Platelets showed both adsorbed and intrinsic antiplasmin activity, but the latter was equivalent to only about 1 % of the total plasma activity.

The Role of Platelets in Fibrinolysis.

Inhibition of plasmin and activation of plasminogen by platelet-poor plasma, intact, lysed and thrombin-aggregated platelet-rich plasma, and washed platelets was studied by means of fibrin-agar plates. No significant activation of plasminogen by platelets could be demonstrated. Maximal inhibition of plasmin occurred after 2–3 hr incubation with either platelet-rich or platelet-poor plasma; in each case the kinetics of the reaction were suggestive of non-competitive inhibition. Platelets showed both adsorbed and intrinsic anti-plasmin activity, but the latter was equivalent to only about 1% of the total plasma activity.