A Comparative Study of Platelet Aggregation in Man and Laboratory Animals

1970 ◽  
Vol 24 (03/04) ◽  
pp. 385-394 ◽  
Author(s):  
D. C Macmillan ◽  
A. K SIM
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Comparative Study ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Thromboembolic Disease ◽  
Considerable Importance ◽  
Laboratory Animals ◽  
Platelet Thrombi

SummaryWhen some human platelets were aggregated in vitro by exogenous adenosine diphosphate (ADP) or adrenaline they released their own ADP. As ADP is the final stimulator of most aggregation, this ability to produce its own release gave a self- propagating secondary aggregation (SA) which could be marked in certain individuals and diseased states. In a survey of several animals, this ability to produce self- propagating aggregation was also found in a marked form in cats (which can form systemic platelet thrombo-emboli) and to a less extent in baboons and some dogs. This property of the platelets of humans and cats could be an important factor in their ability to form platelet thrombi more easily than other mammals. Thus, SA and its inhibition by drugs may be of considerable importance in the management of thromboembolic disease and a study of such agents carried out in these animals may be reasonably regarded as a relevant and useful preliminary to clinical trials in man.

Interactions Between Blood Platelets and Vascular Endothelium in vitro Studies

1979 ◽  
Author(s):  
M.A. Gimbrone ◽  
K.D. Curwen ◽  
R. I. Handin
Keyword(s):  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Potent Inhibitor ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Primary Cultures ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Platelet Adherence

Endothelial cells (EC) can actively influence the hemostatic response at sites of vascular injury through multiple mechanisms. For example, EC can degrade adenosine diphosphate, release plasminogen activator, and synthesize prostacyclin (PGI2), a potent inhibitor of platelet aggregation. We have examined whether PGI2 also might account for the normal lack of platelet adherence to the uninjured EC surface. In a monolayer adherence assay, radiolabeled human platelets in citrated plasma showed minimal interaction with primary cultures of human EC (<1 platelet adhering per cell). Platelets from aspirin-treated and untreated donors behaved similarly. However, aspirin pretreatment of EC consistently resulted in ~2-fold increases in platelet adherence which could be completely abolished by exogenous PGI2 (0.5–1.0 μg/ml). SV40-transformed human EC (SVHEC), which are deficient in PGI2 production compared to primary EC, showed 10-30 times more platelet adherence. Exogenous PGI2 produced a dose - related (.001-1.0 μg/ml) decrease in platelet adherence to SVHEC but did not result in the basal levels observed with normal EC monolayers. These data suggest that : 1) In addition to its effects on platelet aggregation, PGI2 can influence platelet endothelial cell interactions; 2) The increased platelet reactivity of transformed EC is associated with, but not completely attributable, to decreased PGI2 production; and 3) Factors other than PGI2 may play a role in the thromboresistance of normal vascular endothelium.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 286-292 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Adenosine Diphosphate ◽  
Causative Factor ◽  
Respiratory Arrest ◽  
Platelet Thrombi ◽  
Eventual Death ◽  
The Brain

SummaryProstaglandins E1 and ω-homo-E1 which were shown previously to inhibit adenosine diphosphate (ADP)-induced platelet aggregation in vitro have now been found to inhibit this process also in vivo. Both prostaglandins inhibit transient thrombocytopenia induced by intravenous injection of ADP; PGE1 increases also the LD 50 of ADP when injected in high amounts into young rats. In both cases platelet aggregation in vivo is the primary cause of the phenomena observed.The symptoms observed on overdosing ADP by intravenous injection are unconsciousness within 10-20 sec after completion of the injection immediately followed by respiratory arrest and eventual death of the animal, generally within 10 min. It seems that blocking of the supply of blood to the brain by platelet thrombi, which on histological examination were found to occlude blood vessels in different organs, is the most important causative factor of the symptoms observed.

Effects of Lead Acetate on Platelet Aggregation, Ultrastructure and Serotonin Release

1971 ◽  
Vol 26 (03) ◽  
pp. 455-466 ◽  
Author(s):  
R. B Davis ◽  
G. C Holtz
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Lead Acetate ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Human Platelets ◽  
Serotonin Release ◽  
Aggregation Of Platelets

SummaryThe effects of lead on blood platelet function and ultrastructure have been investigated. Lead acetate was injected intravenously in 27 rats and was added to rat and human platelet rich plasma in vitro. In vitro studies showed that concentrations of 2.5 × 10-3 M lead acetate reduced or blocked aggregation of rat and human platelets by adenosine diphosphate, collagen, and thrombin. Radioactive serotonin release from human platelets was inhibited by 10-4 M lead acetate. One hour after the injection of lead, platelet aggregation by thrombin was reduced, but platelet aggregation by adenosine diphosphate and collagen showed little change. Three days after lead, aggregation of platelets by collagen and thrombin was blocked and aggregation by adenosine diphosphate reduced. Thrombocytopenia was present 4 days after intravenous lead acetate. Electron micrographs of platelets showed that the mean number of mitochondria per platelet was increased, whereas alpha granules were reduced. Dense bodies were not significantly changed. Lead acetate affects platelet function in concentrations reported in human bone marrow in lead poisoning, and may relate to the binding of free sulfhydryl groups by lead.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 293-298 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Primary Role ◽  
Electric Stimulus ◽  
Platelet Thrombi

SummaryIt was shown previously that prostaglandin E1 (PGE1) inhibits the aggregation of blood platelets in vitro whereas PGF1α does not; in vivo, PGE1 inhibits in rats the action of intravenously injected adenosine diphosphate. Locally administered PGE1 is found in the present experiment to inhibit in rats the formation and growth of platelet thrombi, induced by an electric stimulus in cortical veins. PGF1α appeared to be inactive.The morphology of platelet thrombi induced by an electric stimulus is shown. The probability of a primary role of erythrocytes in the formation of this type of thrombi is discussed.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

The Mechanism of Platelet Aggregation Induced by HLA-Related Antibodies

1996 ◽  
Vol 76 (05) ◽  
pp. 774-779 ◽  
Author(s):  
John T Brandt ◽  
Carmen J Julius ◽  
Jeanne M Osborne ◽  
Clark L Anderson
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Complement Activation ◽  
Thromboembolic Disease ◽  
Clinical Samples ◽  
Hla Antigen ◽  
Aggregation Response ◽  
Immune Mediated ◽  
Dependent Pathway

SummaryImmune-mediated platelet activation is emerging as an important pathogenic mechanism of thrombosis. In vitro studies have suggested two distinct pathways for immune-mediated platelet activation; one involving clustering of platelet FcyRIIa, the other involving platelet-associated complement activation. HLA-related antibodies have been shown to cause platelet aggregation, but the mechanism has not been clarified. We evaluated the mechanism of platelet aggregation induced by HLA-related antibodies from nine patients. Antibody to platelet FcyRIIa failed to block platelet aggregation with 8/9 samples, indicating that engagement of platelet FcyRIIa is not necessary for the platelet aggregation induced by HLA-related antibodies. In contrast, platelet aggregation was blocked by antibodies to human C8 (5/7) or C9 (7/7). F(ab’)2 fragments of patient IgG failed to induce platelet activation although they bound to HLA antigen on platelets. Intact patient IgG failed to aggregate washed platelets unless aged serum was added. The activating IgG could be adsorbed by incubation with lymphocytes and eluted from the lymphocytes. These results indicate that complement activation is involved in the aggregation response to HLA-related antibodies. This is the first demonstration of complement-mediated platelet aggregation by clinical samples. Five of the patients developed thrombocytopenia in relationship to blood transfusion and two patients developed acute thromboembolic disease, suggesting that these antibodies and the complement-dependent pathway of platelet aggregation may be of clinical significance.

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

1976 ◽  
Vol 36 (02) ◽  
pp. 376-387 ◽  
Author(s):  
Teruhiko Umetsu ◽  
Kazuko Sanai ◽  
Tadakatsu Kato
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Human Platelets ◽  
Rabbit Platelet ◽  
Rabbit Platelets ◽  
Β Blocker ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions

SummaryThe effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

Reaction of Acetaldehyde with Human Platelets

1992 ◽  
Vol 67 (01) ◽  
pp. 126-130 ◽  
Author(s):  
Olivier Spertini ◽  
Jacques Hauert ◽  
Fedor Bachmann
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Action ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Reaction Medium ◽  
Human Platelets ◽  
Membrane Glycoproteins ◽  
Neutral Ph

SummaryPlatelet function defects observed in chronic alcoholics are not wholly explained by the inhibitory action of ethanol on platelet aggregation; they are not completely reproduced either in vivo by short-term ethanol perfusion into volunteers or in vitro by the addition of ethanol to platelet-rich plasma. As acetaldehyde (AcH) binds to many proteins and impairs cellular activities, we investigated the effect of this early degradation product of ethanol on platelets. AcH formed adducts with human platelets at neutral pH at 37° C which were stable to extensive washing, trichloracetic acid hydrolysis and heating at 100° C, and were not reduced by sodium borohydride. The amount of platelet adducts formed was a function of the incubation time and of the concentration of AcH in the reaction medium. At low AcH concentrations (<0.2 mM), platelet bound AcH was directly proportional to the concentration of AcH in the reaction medium. At higher concentrations (≥0.2 mM), AcH uptake by platelets tended to reach a plateau. The amount of adducts was also proportional to the number of exposures of platelets to pulses of 20 pM AcH.AcH adducts formation severely impaired platelet aggregation and shape change induced by ADP, collagen and thrombin. A positive correlation was established between platelet-bound AcH and inhibition of aggregation.SDS-PAGE analysis of AcH adducts at neutral pH demonstrated the binding of [14C]acetaldehyde to many platelet proteins. AcH adduct formation with membrane glycoproteins, cytoskeleton and enzymes might interfere with several steps of platelet activation and impair platelet aggregation.This in vitro study shows that AcH has a major inhibitory action on platelet aggregation and may account for the prolonged ex vivo inhibition of aggregation observed in chronic alcoholics even in the absence of alcoholemia.

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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