Inhibition of platelet aggregation and [14C]serotonin release by luciferin: Luciferase preparations

Summary“Early” fibrinogen degradation products are more potent inhibitors of thrombin-induced clotting than “late” products and also interfere with the ability of thrombin to release serotonin from platelets. “Early” and “intermediate” FDP cause moderate inhibition of platelet aggregation induced by adenosine diphosphate or connective tissue particles. Serotonin release by connective tissue particles is probably not inhibited by FDP.

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Inhibition of platelet aggregation by protease inhibitors. Possible involvement of proteases in platelet aggregation

Blood ◽

10.1182/blood.v52.1.1.1 ◽

1978 ◽

Vol 52 (1) ◽

pp. 1-12 ◽

Cited By ~ 20

Author(s):

N Aoki ◽

K Naito ◽

N Yoshida

Keyword(s):

Platelet Aggregation ◽

Protease Inhibitors ◽

Serine Proteases ◽

Human Platelet ◽

Serotonin Release ◽

Second Phase ◽

Inhibition Of Platelet Aggregation ◽

Naturally Occurring ◽

Human Platelet Aggregation ◽

Platelet Receptor

Abstract The possible participation of proteases in human platelet aggregation was explored using various protease inhibitors and substrates. Protease inhibitors used included naturally occurring inhibitors of serine proteases and synthetic inhibitors that modify the active site of protease. Substrates used were synthetic substrates for the trypsin type as well as for the chymotrypsin type of protease. All these inhibitors and substrates inhibited platelet aggregation and serotonin release induced by ADP, collagen, epinephrine, or thrombin. In ADP- and epinephrine-induced platelet aggregation the second phase of aggregation was most efficiently inhibited. The inhibitors suppressed the formation of malondialdehyde during platelet aggregation. Release by aggregating agents of arachidonate and its metabolites from indomethacin-treated platelets as well as nontreated platelets was also inhibited. The inhibitors apperar to interact with stimulated platelets but not with unstimulated platelets. These observations suggest that the interaction of an aggregating agent with its platelet receptor activates a unique precursor serine protease that in turn activates platelet phospholipase to liberate arachidonic acid (the precursor of the potent platelet aggregating agent thromboxane A2) from platelet phospholipids.

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3’5’-Adenosine Diphosphate (3′5′ADP):A Physiological Inhibitor of Platelet Aggregation and Platelet Release Reaction

10.1055/s-0039-1680423 ◽

1977 ◽

Author(s):

K. Subbarao ◽

K. Jaya

Keyword(s):

Platelet Aggregation ◽

Coenzyme A ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Serotonin Release ◽

Dependent Manner ◽

Release Reaction ◽

Inhibition Of Platelet Aggregation ◽

Vitro Effect ◽

Aggregation Of Platelets

Certain analogues of adenosine have been shown to inhibit ADP-induced platelet aggregation. We therefore studied the in vitro effect of 3′5′ADP and coenzyme A on human platelet aggregation and [14C]-serotonin release reaction induced by the addition of ADP, thrombin, collagen and epinephrine to human platelet rich plasma (PRP). It was found that coenzyme A Li3·2H2O at a concentration of 0.12 mM strongly inhibited ADP-induced platelet aggregation of PRP but did not show similar effect on the aggregation of platelets induced by other aggregating agents. The 3′5′ADP which is a part of coenzyme A structure, on the other hand, inhibited both ADP and thrombin induced platelet aggregation. The extent of inhibition of platelet aggregation by coenzyme A and 3′5′ADP was found to depend upon the concentration of the inhibitor and the incubation time. Whereas 3′5′ADP Li2·3H2O at a concentration of 10 μM produced about 70% inhibition of ADP-induced platelet aggregation of human PRP, total inhibition of thrombin induced platelet aggregation was observed when platelets were incubated with 60 μM of 3′5′ADP. The 3′5′ADP also inhibited the [14C]-adeonsine uptake by platelets in a concentration dependent manner. The inhibitory potency of 3′5′ADP on platelet aggregation was found to be 10-fold higher than that of N6-2′-0-dibutyryl-cyclic 3′5′-adenosine monophosphate. The inhibition of platelet aggregation by coenzyme A and 3′5′ADP was always accompanied by the inhibition of [14C]-serotonin release reaction. If coenzyme A and 3′5′ADP are indeed physiological inhibitors of platelet aggregation, then aggregation of platelets should depend on metabolic events that regulate the concentration of these agents in blood.

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Inhibition of platelet aggregation by protease inhibitors. Possible involvement of proteases in platelet aggregation

Blood ◽

10.1182/blood.v52.1.1.bloodjournal5211 ◽

1978 ◽

Vol 52 (1) ◽

pp. 1-12

Author(s):

N Aoki ◽

K Naito ◽

N Yoshida

Keyword(s):

Platelet Aggregation ◽

Protease Inhibitors ◽

Serine Proteases ◽

Human Platelet ◽

Serotonin Release ◽

Second Phase ◽

Inhibition Of Platelet Aggregation ◽

Naturally Occurring ◽

Human Platelet Aggregation ◽

Platelet Receptor

The possible participation of proteases in human platelet aggregation was explored using various protease inhibitors and substrates. Protease inhibitors used included naturally occurring inhibitors of serine proteases and synthetic inhibitors that modify the active site of protease. Substrates used were synthetic substrates for the trypsin type as well as for the chymotrypsin type of protease. All these inhibitors and substrates inhibited platelet aggregation and serotonin release induced by ADP, collagen, epinephrine, or thrombin. In ADP- and epinephrine-induced platelet aggregation the second phase of aggregation was most efficiently inhibited. The inhibitors suppressed the formation of malondialdehyde during platelet aggregation. Release by aggregating agents of arachidonate and its metabolites from indomethacin-treated platelets as well as nontreated platelets was also inhibited. The inhibitors apperar to interact with stimulated platelets but not with unstimulated platelets. These observations suggest that the interaction of an aggregating agent with its platelet receptor activates a unique precursor serine protease that in turn activates platelet phospholipase to liberate arachidonic acid (the precursor of the potent platelet aggregating agent thromboxane A2) from platelet phospholipids.

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Differing Susceptibilities of Platelets from Normal Individuals and Patients with von Willebrand’s Disease to Attack by Quinine- and Quinidine-Dependent Antiplatelet Antibodies

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646537 ◽

1989 ◽

Vol 61 (01) ◽

pp. 111-116

Author(s):

Sharron L Pfueller ◽

Robyn A Bilston ◽

Dana Logan ◽

Rosemary David ◽

Ian G Sloan ◽

...

Keyword(s):

Platelet Aggregation ◽

Platelet Rich Plasma ◽

Serotonin Release ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Antiplatelet Antibodies ◽

Normal Plasma ◽

Igg Binding ◽

Normal Individuals ◽

Drug Dependent

SummaryReactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand’s disease (vWd). One quinine-dependent antibody (Q. Ab) caused platelet aggregation and [14C] serotonin release with only 7 of 12 normal donors, while another Q. Ab and a quinidine-dependent antibody (Qd. Ab) caused aggregation and release with all 12. Drug- dependent IgG binding and PF 3 availability induced by the antibodies were, however, comparable in all donors. Differences in responsiveness were associated with platelets and not plasma. vWd platelets showed normal drug-dependent IgG binding, but decreased aggregation and serotonin release to most drug- dependent antibodies. Responsiveness was not restored by purified vWf:Ag, but, in one case, was corrected by normal plasma or cryoprecipitate. Drug-dependent binding of the Q. Ab which caused variable responsiveness in normals was to the same platelet antigens (GPIb and GPIIIa) in both normal and vWd platelets and did not require plasma components. Reduced PF 3 availability was seen with some antibodies in some vWd patients. Plasma from two of these patients inhibited aggregation of normal platelets to Q. Ab and one of these inhibited aggregation to ADP. Antiplatelet antibodies were detected in these two plasmas by ELISA. Thus some Q. Ab produce different responses with platelets from different donors. In vWd, reduced responsiveness to Q.Ab and Qd. Ab may result from production of inhibitory antiplatelet antibodies.

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Effects of Halothane on Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650105 ◽

1980 ◽

Vol 44 (03) ◽

pp. 143-145 ◽

Cited By ~ 19

Author(s):

J Dalsgaard-Nielsen ◽

J Gormsen

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Human Platelets ◽

Halothane Anaesthesia ◽

Inhibition Of Platelet Aggregation ◽

Transient Impairment ◽

High Concentrations ◽

Uptake And Release ◽

Platelet Functions

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.

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The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651610 ◽

1993 ◽

Vol 69 (04) ◽

pp. 344-350 ◽

Cited By ~ 175

Author(s):

B H Chong ◽

J Burgess ◽

F Ismail

Keyword(s):

Platelet Aggregation ◽

Heparin Therapy ◽

Serotonin Release ◽

Point System ◽

Control Groups ◽

Heparin Induced Thrombocytopenia ◽

Heparin Concentration ◽

Release Test ◽

The Mean ◽

Normal Controls

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

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Platelet Coagulant Activities and Retinal Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651475 ◽

1977 ◽

Vol 38 (02) ◽

pp. 0399-0406 ◽

Cited By ~ 10

Author(s):

Peter N. Walsh ◽

Richard E. Goldberg ◽

Richard L. Tax ◽

Larry E. Magargal

Keyword(s):

Platelet Aggregation ◽

Venous Thrombosis ◽

Retinal Vein Occlusion ◽

Serotonin Release ◽

Platelet Factor ◽

Trigger Mechanism ◽

Local Conditions ◽

Plasma Coagulation ◽

Vein Thrombosis ◽

Vein Occlusion

SummaryTo determine whether platelets play a role in the pathogenesis of retinal vein occlusion (RVO), platelets and coagulation were evaluated in 28 patients with RVO. Platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation were 2–4 fold increased in 9 patients with acute primary RVO but not in patients with acute secondary (10 patients) or chronic (9 patients) RVO. Platelet factor 3 activity, platelet aggregation, serotonin release by platelets and plasma coagulation were normal in all patients. Platelets may provide a trigger mechanism for venous thrombosis in the eye when local conditions permit.

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Inhibition of Fibrinolytic Activity In-Vivo by Dexamethasone Is Counterbalanced by an Inhibition of Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656320 ◽

1992 ◽

Vol 68 (01) ◽

pp. 069-073 ◽

Cited By ~ 16

Author(s):

J J J van Giezen ◽

J W C M Jansen

Keyword(s):

Platelet Aggregation ◽

Fibrinolytic Activity ◽

Ex Vivo ◽

Dose Range ◽

Coagulation System ◽

Loop Model ◽

Prothrombotic State ◽

Inhibition Of Platelet Aggregation ◽

Pai 1

SummaryDexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1–3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation.

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Inhibition of Platelet Aggregation by Human Placenta

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657866 ◽

1985 ◽

Vol 54 (02) ◽

pp. 431-437 ◽

Cited By ~ 1

Author(s):

M J Dembélé-Duchesne ◽

A Laghchim Lahlou ◽

H Thaler-Dao ◽

A Crastes de Paulet

Keyword(s):

Fatty Acid ◽

Platelet Aggregation ◽

Human Placenta ◽

Cyclooxygenase Inhibitor ◽

Synthetase Inhibitor ◽

Inhibition Of Platelet Aggregation ◽

Thromboxane Synthetase ◽

Rabbit Platelets ◽

High Doses ◽

Induced Aggregation

SummaryHuman placental cytosol inhibits platelet aggregation induced by high doses of collagen. The aim of this study was to investigate whether this anti-aggregating activity was caused only by the presence of various activities already described in the placenta (an ADP-consuming enzyme, a fatty acid cyclooxygenase inhibitor, and a thromboxane synthetase inhibitor) or whether another factor was present.Heating the cytosol at 50° C for 6 min destroyed the inhibitor of collagen-induced aggregation. ADPase and the AA pathway inhibitors were not modified by this treatment. We therefore show the presence of an additional anti-aggregating factor: it is destroyed by heating at 50° C.We also tested for the presence of an inhibitor of AA release in the placental cytosol using three different methods (rabbit platelets in PRP, washed rabbit platelets, and NRK fibroblasts) but no inhibition could be evidenced.We conclude that this new anti-aggregating factor, which is probably a protein, acts neither through AA release inhibition nor AA cascade inhibition.

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