Activation of the blood fibrinolytic enzyme system by platelets

1964 ◽  
Vol 206 (6) ◽  
pp. 1255-1261 ◽  
Author(s):  
W. O. Reid ◽  
M. J. Silver
Keyword(s):  
Fibrinolytic Activity ◽  
Room Temperature ◽  
Enzyme System ◽  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Aminocaproic Acid ◽  
Clot Retraction ◽  
Oxalate Solution ◽  
Epsilon Aminocaproic Acid ◽  
Inhibitor Of Plasminogen Activator

Fibrinolytic activity in human blood develops after the occurrence of viscous metamorphosis (VM) of platelets. Freshly drawn venous blood was held at room temperature until spontaneous VM of platelets occurred and then introduced into oxalate solution to prevent coagulation. As compared to the control (blood added to anticoagulant before VM) plasma of such samples exhibited increased fibrinolytic activity, detected by increased serial thrombin times. Clots from platelet-rich plasma exhibited an increase in the convergence of branches of the thrombelastograph and a decrease in weight after incubation for 24 hr or more. The increase in branch convergence was roughly proportional to the platelet count and was reduced or absent in thrombocytopenic blood or platelet-poor plasma. Dimethylsulfoxide blocked VM and prevented branch convergence (without preventing clot retraction). Epsilon-aminocaproic acid, an inhibitor of plasminogen activator, blocked or inhibited fibrinolytic activity without arresting VM. This evidence suggests that platelets contain significant proactivator or activator of plasminogen (or a factor which initiates their activity) which is released when VM occurs.

Human Platelet Acetylcholinesterase: The Effects of Anticholinesterases on Platelet Function

1979 ◽  
Vol 42 (05) ◽  
pp. 1615-1619 ◽  
Author(s):  
Martin J Smith ◽  
Boyd Braem ◽  
Kent D Davis
Keyword(s):  
Platelet Function ◽  
Ache Activity ◽  
Room Temperature ◽  
Platelet Rich Plasma ◽  
Complete Inhibition ◽  
Clot Retraction ◽  
Plasma Clot ◽  
Normal Platelet ◽  
Aggregation Factor

SummaryPlatelet acetylcholinesterase (AChE) activity was measured in gel-filtered platelet preparations. Three different anticholinesteratic agents (eserine, neostigmine, and diiso- propylphosphorofluoridate) at final concentrations of 10 μM caused complete inhibition of AChE activity after 30 min incubation at room temperature with either platelet-rich plasma or gel-filtered platelets. Complete inhibition of platelet AChE had no effect on platelet aggregation, factor-3 availability, and plasma clot retraction. We conclude that platelet membrane AChE activity is not required for normal platelet function as measured by these in vitro parameters.

Clot Retraction and Fibrinolysis

1963 ◽  
Vol 9 (2) ◽  
pp. 182-187 ◽  
Author(s):  
Murray Weiner
Keyword(s):  
Fibrinolytic Activity ◽  
Calcium Concentration ◽  
Enzyme System ◽  
Clot Lysis ◽  
Clot Retraction

Abstract Three different systems were employed for parallel observations of clot lysis and retraction. Potassium and calcium concentration was found to influence significantly these phenomena in some systems but not in others. Under a variety of conditions, both retraction and fibrinolysis are affected in a parallel manner, suggesting that the retraction state of a clot used as a substrate may influence the apparent fibrinolytic activity of an enzyme system.

scholarly journals Plasminogen interactions with platelets in plasma

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1530-1535 ◽  
Author(s):  
B Adelman ◽  
A Rizk ◽  
E Hanners
Keyword(s):  
Monoclonal Antibody ◽  
Binding Site ◽  
Platelet Rich Plasma ◽  
Aminocaproic Acid ◽  
Binding Domains ◽  
Fibrinogen Binding ◽  
Platelet Binding ◽  
Epsilon Aminocaproic Acid ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In this report we used a fluorescent flow cytometry-based assay to examine plasminogen binding to platelets in plasma. Our data indicate that platelets activated in platelet-rich plasma (PRP) by adenosine-5′- diphosphate (ADP) or thrombin bind plasminogen to their surface. Fab fragments of the monoclonal antibody LJ-CP8 that are directed against the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex inhibit both plasminogen and fibrinogen binding to ADP-stimulated platelets as does 5 mmol/L EDTA. Platelet aggregation and plasminogen and fibrinogen binding are also concurrently inhibited by the Gly-Arg- Asp (RGD) analogue Gly-Arg-Gly-Asp-Ser (GRGDS) when it is added to PRP before ADP stimulation. The scrambled peptide analogue SDGRG has no effect. The monoclonal antibody 6D1, directed against the von Willebrand factor binding site on GPIb, has no effect on plasminogen- platelet binding, nor does antithrombospondin antibody. epsilon- Aminocaproic acid (EACA), however, inhibits plasminogen binding to ADP- activated platelets. These data indicate that plasminogen binds to platelets activated in plasma, that binding occurs on platelet GPIIb/IIIa, and that binding may be mediated via plasminogen association with fibrinogen via lysine binding domains. Finally, we found both plasminogen and fibrinogen on resting platelets in PRP and demonstrated that they are equally displaced by EDTA, LJ-CP8, and 10E5 (an additional anti-GPIIb/IIIa monoclonal antibody). Plasminogen is also equally displaced by EACA. These data suggest that plasminogen is also bound to GPIIb/IIIa on resting platelets, possibly also via interaction with fibrinogen.

A method for monitoring antifibrinolytic therapy in patients with ruptured intracranial aneurysms

1981 ◽  
Vol 54 (1) ◽  
pp. 12-15 ◽  
Author(s):  
Kim J. Burchiel ◽  
Gottfried Schmer
Keyword(s):  
Fibrinolytic Activity ◽  
Intracranial Aneurysms ◽  
Aminocaproic Acid ◽  
Content Type ◽  
Antifibrinolytic Therapy ◽  
Epsilon Aminocaproic Acid ◽  
Ruptured Intracranial Aneurysms ◽  
Control Plasma ◽  
Fine Print

✓ A rapid fluorometric assay technique has been utilized to assess the degree of fibrinolytic inhibition in 20 patients with ruptured intracranial aneurysms treated with epsilon-aminocaproic acid (EACA). This method quantitates the available plasminogen activity (APA) of plasma, and has proven to be a reliable means of monitoring antifibrinolytic therapy. Determination of the plasma APA also permits correlation of the level of fibrinolytic activity with putative complications of EACA therapy. Normal control plasma APA was 3.1 ± 0.7 CTA units/ml, but in patients with subarachnoid hemorrhage (SAH), pretreatment fibrinolytic activity was supranormal at 3.78 ± 0.88 CTA units/ml. During continuous intravenous administration of EACA (1.5 gm/hr) in patients with SAH, the plasma fibrinolytic activity was decreased to 0.9 ± 0.31 CTA units/ml. A case is described which exemplifies the use of this assay. In addition, an approach to monitoring antifibrinolytic therapy using the plasma APA is proposed.

scholarly journals THE ENHANCEMENT OF CHLOROFORM-INDUCED PLASMA PROTEOLYTIC ACTIVITY BY EPSILON AMINOCAPROIC ACID

1962 ◽  
Vol 115 (4) ◽  
pp. 695-706 ◽  
Author(s):  
Virginia H. Donaldson ◽  
Oscar D. Ratnoff
Keyword(s):  
Ionic Strength ◽  
Proteolytic Activity ◽  
Fibrinolytic Activity ◽  
Proteolytic Enzyme ◽  
Aminocaproic Acid ◽  
Heat Stability ◽  
Hydrolytic Activity ◽  
Casein Hydrolysis ◽  
Epsilon Aminocaproic Acid ◽  
Optimal Ph

The proteolytic activity in chloroform-treated plasma euglobulins has been attributed to plasmin. Plasmin can digest both casein and fibrin. Epsilon aminocaproic acid, which inhibits the activation of plasminogen, the precursor of plasmin, by streptokinase, urokinase, and tissue activators enhanced the development of casein hydrolytic activity in a mixture of chloroform and plasma euglobulins. Fibrinolytic activity was also enhanced, but this was evident only if the epsilon aminocaproic acid was removed from the chloroform-treated euglobulins prior to assay. The reasons for the paradoxical enhancement of chloroform-induced casein hydrolysis by euglobulins containing epsilon aminocaproic acid are unclear. However, studies of optimal pH, heat stability, and the effect of ionic strength on the activation of the precursor of this proteolytic enzyme do not differentiate it from plasminogen.

scholarly journals The effect of some epsilon-aminocaproic acid derivatives on platelet responses.

2004 ◽  
Vol 51 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Irena Bruzgo ◽  
Marian Tomasiak ◽  
Halina Stelmach ◽  
Krystyna Midura-Nowaczek
Keyword(s):  
Platelet Rich Plasma ◽  
Aminocaproic Acid ◽  
Inhibitory Effect ◽  
Cysteine Hydrochloride ◽  
Similar Inhibitory Effect ◽  
Coated Surfaces ◽  
Epsilon Aminocaproic Acid ◽  
Induced Aggregation ◽  
Synthetic Derivatives ◽  
Adhesion Of Platelets

epsilon-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an increased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. epsilon-aminocaproyl-L-leucine hydrochloride (HCl*H-EACA-L-Leu-OH), II. epsilon-aminocaproyl-L-(S-benzyl)-cysteine hydrochloride (HCl*H-EACA-L-Cys(S-Bzl)-OH) and III. epsilon-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their integrity. It was found that: 1. as judged by LDH release test, none of the tested compounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the synthetic derivatives inhibited much stronger the ADP- and collagen-induced aggregation of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced thrombotic properties of these derivatives compared to EACA.

scholarly journals Plasminogen interactions with platelets in plasma

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1530-1535
Author(s):  
B Adelman ◽  
A Rizk ◽  
E Hanners
Keyword(s):  
Monoclonal Antibody ◽  
Binding Site ◽  
Platelet Rich Plasma ◽  
Aminocaproic Acid ◽  
Binding Domains ◽  
Fibrinogen Binding ◽  
Platelet Binding ◽  
Epsilon Aminocaproic Acid ◽  
Von Willebrand ◽  
Willebrand Factor

In this report we used a fluorescent flow cytometry-based assay to examine plasminogen binding to platelets in plasma. Our data indicate that platelets activated in platelet-rich plasma (PRP) by adenosine-5′- diphosphate (ADP) or thrombin bind plasminogen to their surface. Fab fragments of the monoclonal antibody LJ-CP8 that are directed against the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex inhibit both plasminogen and fibrinogen binding to ADP-stimulated platelets as does 5 mmol/L EDTA. Platelet aggregation and plasminogen and fibrinogen binding are also concurrently inhibited by the Gly-Arg- Asp (RGD) analogue Gly-Arg-Gly-Asp-Ser (GRGDS) when it is added to PRP before ADP stimulation. The scrambled peptide analogue SDGRG has no effect. The monoclonal antibody 6D1, directed against the von Willebrand factor binding site on GPIb, has no effect on plasminogen- platelet binding, nor does antithrombospondin antibody. epsilon- Aminocaproic acid (EACA), however, inhibits plasminogen binding to ADP- activated platelets. These data indicate that plasminogen binds to platelets activated in plasma, that binding occurs on platelet GPIIb/IIIa, and that binding may be mediated via plasminogen association with fibrinogen via lysine binding domains. Finally, we found both plasminogen and fibrinogen on resting platelets in PRP and demonstrated that they are equally displaced by EDTA, LJ-CP8, and 10E5 (an additional anti-GPIIb/IIIa monoclonal antibody). Plasminogen is also equally displaced by EACA. These data suggest that plasminogen is also bound to GPIIb/IIIa on resting platelets, possibly also via interaction with fibrinogen.

FIBRINOLYTIC ACTION OF RESERPINE IN RATS

1964 ◽  
Vol 42 (1) ◽  
pp. 153-156 ◽  
Author(s):  
J. G. Ashwin ◽  
W. R. Coughlin
Keyword(s):  
Fibrinolytic Activity ◽  
Aminocaproic Acid ◽  
Route Of Administration ◽  
Clot Lysis ◽  
Lysis Time ◽  
Euglobulin Clot Lysis Time ◽  
Epsilon Aminocaproic Acid ◽  
Clot Lysis Time ◽  
Fibrinolytic Action

The plasma fibrinolytic activity in rats was measured by the euglobulin clot lysis time technique after injection of reserpine, serotonin, epsilon-aminocaproic acid, and UML-491. Fibrinolytic activity was increased by reserpine and serotonin, the extent depending on the dosage and route of administration. With serotonin, clot lysis time returned to normal after 6–12 hours. With reserpine, this occurred after 4 days. The antifibrinoiysin E-ACA was able to reduce fibrinolytic activity for more than 24 hours, whether given alone or with reserpine or serotonin. The antiserotonin UML-491 had a paradoxical fibrinolytic enhancing action that lasted for several hours alone, or given with serotonin it increased the fibrinolytic effect of serotonin.

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