Demonstration of a Plasmatic Cofactor Different from Fibrinogen Necessary for Platelet Release by ADP and Adrenaline

1970 ◽  
Vol 24 (03/04) ◽  
pp. 409-418 ◽  
Author(s):  
S Cronberg ◽  
P Kubisz ◽  
J. P Caen
Keyword(s):  
Salicylic Acid ◽  
Acetyl Salicylic Acid ◽  
Secondary Wave ◽  
Platelet Factor ◽  
Washed Platelet ◽  
Release Reaction ◽  
Platelet Aggregates ◽  
Platelet Release ◽  
Second Wave ◽  
Possible Cause

SummarySecondary wave production and release of platelet factor 4 were studied in washed platelet suspensions and citrate plasma. Induction of a secondary wave requires the presence of large aggregates and a plasmatic cofactor different from fibrinogen. Acetyl-salicylic acid inhibited the production of a second wave both in plasma and platelet suspensions. Plasma taken after the intake of acetyl-salicylic acid induced a second wave in platelets harvested before the intake. The possible production of thrombin or allied enzyme inside the platelet aggregates due to changed internal milieu is suggested as a possible cause of the release reaction induced by ADP and adrenaline. Fundamental differences existed between the release induced by ADP and adrenaline and that induced by collagen, kaolin and other particles.

scholarly journals Thrombocytopathia Due to Abnormalities in Platelet Release Reaction—Studies on Six Unrelated Patients

Blood ◽  
1972 ◽  
Vol 39 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Harvey J. Weiss ◽  
John Rogers
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
General Term ◽  
Platelet Factor ◽  
Patients Âgés ◽  
Release Reaction ◽  
Prolonged Bleeding Time ◽  
Adp Release ◽  
Platelet Release ◽  
Induced Aggregation

Abstract The prolonged bleeding time in six unrelated patients ages 24-63, was attributed to impaired platelet aggregation; this could be accounted for by the decreased release of platelet adenosine diphosphate (ADP) that was obtained in all patients. As a consequence of this "platelet release abnormality," collagen-induced platelet aggregation was impaired, the second wave of epinephrine-induced aggregation was decreased (although not invariably absent), and the normal initial wave of ADP-induced aggregation was followed by rapid disaggregation at 37°C. In four patients, the abnormality in collagen-induced aggregation and ADP release appeared to be different than the defect produced by aspirin, whereas two patients appeared to have an "aspirinlike defect." The platelets of all patients adhered normally to connective tissue fibers but were poorly retained in glass bead filters. Other abnormalities included impaired kaolin-induced platelet factor 3 availability in four patients, large platelets (which aggregated normally with bovine fibrinogen) in two, and small platelets in one patient. The general term thrombocytopathia is suggested to describe abnormalities in platelet function; where a specific defect in the release reaction has been demonstrated, "platelet release abnormality" is suggested as an appropriate, specific term.

Effect of Acetyl Salicylic Acid on Platelet Function in Yivo

1975 ◽  
Author(s):  
A. A. Hassanein ◽  
N. Afifi ◽  
M. Badr
Keyword(s):  
Salicylic Acid ◽  
Single Dose ◽  
Platelet Aggregation ◽  
Inhibitory Effect ◽  
Acetyl Salicylic Acid ◽  
Clotting Time ◽  
Significant Prolongation ◽  
Platelet Disaggregation ◽  
Platelet Release ◽  
Coagulation Pathway

The ingestion of a single dose of 300 mg. acetyl salicylic acid (ASA) cause after two hours, significant diminution in ADP-induced platelet aggregation and increase in platelet disaggregation. The calcium-induced platelet aggregation test, a turbidimetric modification of the Chandler tube technique, showed significant prolongation in the onset of aggregation and in the clotting time. A test based on the contact product forming activity of platelets showed inhibition after ASA intake.It is suggested that acetyl salicylic acid in addition to its inhibitory effect on platelet release reaction, also affects primary aggregation by ADP and possibly interferes with the ability of platelets to activate the contact system of the intrinsic blood coagulation pathway.

Hereditary Bleeding Disorder due to Primary Defects in Platelet Release Mechanism

1979 ◽  
Author(s):  
K.K. Wu ◽  
Y.C. Chen ◽  
J. Walasek ◽  
C. Smith
Keyword(s):  
Calcium Ionophore ◽  
Secondary Wave ◽  
Release Mechanism ◽  
Ionophore A23187 ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Genetic Characteristics ◽  
Recurrent Epistaxis ◽  
Platelet Release ◽  
Induced Aggregation

Aspirin-like platelet release defect remains a poorly defined entity. To gain understa nd of its pathophysiologic and genetic characteristics, 5 kindreds were investigated. All 5 propOsiti were females with ages ranging from 26 to 62 years. Each patient had had easy bruising, recurrent epistaxis and hypermenorrhea since early childhood. Abnormalities in release reaction were characterized by an absence of secondary- wave aggregation in response to ADP and epinephrine, a marked reduction of collagen-and arachidonate induced aggregation and a reduc tion in l4C-se rotonin release. The plateiet ADP, ATP content and ATP/ADP ratio were normal in all the patients. Ther elease defect was definitely not due to drug usage. No salicylates were detectable in the blood. Bleeding time war prlonged in only 2 patients. Platelet factor 3 availability was abnormal in approximatly 40% of the affected subjects. The platelet count, morphology and retention, clot retraction and ristocetin-induced aggregation were normal. The inheritance pattern which could be adequately evaluated in 4 kindreds is consistent with an autosomal dominant trait. Calcium ionophore A23187 aggregated the patient platelets normally, indicating that the intracellular calcium transport mechanism is intact in this disorder. We conclude that primary platelet release defectis an entity of he reditary thrombocy topathies with welldefined clinical and laboratory manifes tations.

Granule stores from cellubrevin/VAMP-3 null mouse platelets exhibit normal stimulus-induced release

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1716-1722 ◽  
Author(s):  
Todd D. Schraw ◽  
Tara W. Rutledge ◽  
Garland L. Crawford ◽  
Audrey M. Bernstein ◽  
Amanda L. Kalen ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Null Mouse ◽  
Wild Type ◽  
Platelet Factor ◽  
Release Reaction ◽  
Molecular Machinery ◽  
Platelet Release ◽  
Dense Core Granules ◽  
Platelet Exocytosis ◽  
Induced Aggregation

AbstractIt is widely accepted that the platelet release reaction is mediated by heterotrimeric complexes of integral membrane proteins known as SNAREs (SNAP receptors). In an effort to define the precise molecular machinery required for platelet exocytosis, we have analyzed platelets from cellubrevin/VAMP-3 knockout mice. Cellubrevin/VAMP-3 has been proposed to be a critical v-SNARE for human platelet exocytosis; however, data reported here suggest that it is not required for platelet function. Upon stimulation with increasing concentrations of thrombin, collagen, or with thrombin for increasing time there were no differences in secretion of [3H]-5HT (dense core granules), platelet factor IV (alpha granules), or hexosaminidase (lysosomes) between null and wild-type platelets. There were no gross differences in bleeding times nor in agonist-induced aggregation measured in platelet-rich plasma or with washed platelets. Western blotting of wild-type, heterozygous, and null platelets confirmed the lack of cellubrevin/VAMP-3 in nulls and showed that most elements of the secretion machinery are expressed at similar levels. While the secretory machinery in mice was similar to humans, mice did express apparently higher levels of synaptobrevin/VAMP-2. These data show that the v-SNARE, cellubrevin/VAMP-3 is not a requirement for the platelet release reaction in mice.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

The Effect of the Phospholipase Inhibitor Mepacrine on Platelet Aggregation, the Platelet Release Reaction and Fibrinogen Binding to the Platelet Surface

1981 ◽  
Vol 45 (03) ◽  
pp. 257-262 ◽  
Author(s):  
P D Winocour ◽  
R L Kinlough-Rathbone ◽  
J F Mustard
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Surface ◽  
Release Reaction ◽  
Fibrinogen Binding ◽  
Platelet Release

SummaryWe have examined whether inhibition by mepacrine of freeing of arachidonic acid from platelet phospholipids inhibits platelet aggregation to collagen, thrombin or ADP, and the release reaction induced by thrombin or collagen. Loss of arachidonic acid was monitored by measuring the amount of 14 C freed from platelets prelabelled with 14 C-arachidonic acid. Mepacrine inhibited 14 C loss by more than 80% but did not inhibit thrombin-induced platelet aggregation and had a small effect on release. ADP-induced platelet aggregation did not cause 14 C loss. Mepacrine inhibited ADP-induced platelet aggregation by inhibiting the association of fibrinogen with platelets during aggregation. The effect of mepacrine on fibrinogen binding could be considerably decreased by washing the platelets but the inhibition of 14 C loss persisted. Platelets pretreated with mepacrine and then washed show restoration of aggregation to collagen. Thus, mepacrine has two effects; 1. it inhibits phospholipases, 2. it inhibits fibrinogen binding. Freeing of arachidonic acid is not necessary for platelet aggregation or the release reaction.

Systemic Effects of ADP-induced Platelet Aggregation and Their Modification by Aspirin and by Pyridinolcarbamate

1973 ◽  
Vol 30 (01) ◽  
pp. 178-190 ◽  
Author(s):  
Itsuro Kobayashi ◽  
Paul Didisheim
Keyword(s):  
Platelet Aggregation ◽  
Venous Pressure ◽  
Systemic Effects ◽  
Central Venous ◽  
Platelet Aggregates ◽  
Induced Changes ◽  
Second Wave ◽  
Carotid Arterial ◽  
Arterial Po2

SummaryADP, AMP, or ATP was injected rapidly intravenously in rats. ADP injection resulted in the f olio wing transient changes: a drop in platelet count, a rise in central venous pressure, a fall in carotid arterial PO2, bradycardia, arrhythmia, flutter-fibrillation, and arterial hypotension. AMP and ATP produced some of these same effects; but except for hypotension, their frequency and severity Avere much less than those following ADP.Prior intravenous administration of acetylsalicylic acid or pyridinolcarbamate, two inhibitors of the second wave of ADP-induced platelet aggregation in vitro, significantly reduced the frequency and severity of all the above ADP-induced changes except hypotension. These observations suggest that many of the changes (except hypotension) observed to follow ADP injection are produced by platelet aggregates which lodge transiently in various microcirculatory beds then rapidly disaggregate and recirculate.

Inhibition by Phenol and Phenolic Acids of Platelet Release Reaction

1973 ◽  
Vol 30 (02) ◽  
pp. 334-338 ◽  
Author(s):  
Felisa C. Molinas
Keyword(s):  
Renal Failure ◽  
Phenolic Compounds ◽  
Phenolic Acids ◽  
Platelet Function ◽  
Deleterious Effect ◽  
Release Reaction ◽  
Contributory Factors ◽  
Adp Release ◽  
Platelet Release

SummaryIt has been postulated that the high phenol and phenolic acids plasmatic levels found in patients with chronic renal failure are contributory factors in the abnormal platelet function described in these patients. This hypothesis was corroborated by “in vitro” studies showing the deleterious effect of these compounds on certain platelet function after pre-incubation of PRP with phenol and phenolic compounds. The present studies were conducted to determine the influence of phenolic compounds on platelet release reaction. It was found that phenol inhibited from 62.5 to 100% the effect of the aggregating agents thrombin, adrenaline and ADP on platelet 5-HT-14C release. The phenolic acids p-, m-, and o-HPAA inhibited from 36.35 to 94.8% adrenaline and ADP-induced platelet 5-HT-14C release. Adrenaline-induced platelet ADP release was inhibited from 27.45 to 38.10% by the phenolic compounds. These findings confirm the hypothesis that phenolic compounds interfere with platelet function through the inhibition of the release reaction.

Release, Aggregation and Lysis of Human Platelets by Antilymphocyte Globulin and Antiplatelet Serum

1976 ◽  
Vol 36 (02) ◽  
pp. 411-423 ◽  
Author(s):  
Nicholas Lekas ◽  
J. C Rosenberg
Keyword(s):  
Platelet Aggregation ◽  
Gamma Globulin ◽  
Human Platelets ◽  
Plasma Medium ◽  
Release Reaction ◽  
Clinical Events ◽  
Thrombotic Complications ◽  
Platelet Release ◽  
Free Media

SummaryHuman platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.

Platelet Aggregation Induced in Vitro by Therapeutic Ultrasound

1977 ◽  
Vol 38 (03) ◽  
pp. 0640-0651 ◽  
Author(s):  
B. V Chater ◽  
A. R Williams
Keyword(s):  
Platelet Aggregation ◽  
Direct Action ◽  
Adenosine Diphosphate ◽  
Ultrasonic Cavitation ◽  
Related Phenomenon ◽  
Release Reaction ◽  
Physical Conditions ◽  
Platelet Aggregates ◽  
Active Substances

SummaryPlatelets were found to aggregate spontaneously when exposed to ultrasound generated by a commercial therapeutic device. At a given frequency, aggregation was found to be a dose-related phenomenon, increasing intensities of ultrasound inducing more extensive and more rapid aggregation. At any single intensity, the extent aggregation was increased as the frequency of the applied ultrasound was decreased (from 3.0 to 0.75 MHz).Ultrasound-induced platelet aggregation was found to be related to overall platelet sensitivity to adenosine diphosphate. More sensitive platelets were found to aggregate spontaneously at lower intensities of sound, and also the maximum extent of aggregation was found to be greater. Examination of ultrasound-induced platelet aggregates by electron microscopy demonstrated that the platelets had undergone the release reaction.The observation that haemoglobin was released from erythrocytes in whole blood irradiated under identical physical conditions suggests that the platelets are being distrupted by ultrasonic cavitation (violent gas/bubble oscillation).It is postulated that overall platelet aggregation is the result of two distinct effects. Firstly, the direct action of ultrasonic cavitation disrupts a small proportion of the platelet population, resulting in the liberation of active substances. These substances produce aggregation, both directly and indirectly by inducing the physiological release reaction in adjacent undamaged platelets.

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