scholarly journals Adenosine Diphosphate Induced Aggregation and Release Reaction in Heparinized Platelet Rich Plasma

1977 ◽  
Author(s):  
S. Heptinstall ◽  
G.P. Mulley
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Exchange Chromatography ◽  
Second Phase ◽  
Release Reaction ◽  
Ionised Calcium ◽  
Irreversible Aggregation ◽  
Induced Aggregation ◽  
Citrate Release

Preparations of heparinized platelet rich plasma (PRP) from 54 different volunteers were examined to determine the extent of platelet aggregation and release reaction both in the absence and presence of citrate. Platelet aggregation was studied in fresh untreated samples of PRP using a range of concentrations of ADP. To study release reaction platelets in a portion of each preparation were labelled with 3H-5-hydroxytryptamine. Released radioactivity was measured after stirring with ADP or with ADP and citrate.Even in the absence of citrate release was considerable in 26 of the preparations. There was a good correlation between extent of aggregation and extent of release reaction. When second phase aggregation occurred release was extensive, when release was low or absent the higher concentrations of ADP were required to bring about “irreversible” aggregation. Whenever citrate was present release reaction was enhanced. Enhanced release reaction was also observed in PRP in which the bulk of plasma calcium had been exchanged for sodium by ion exchange chromatography.It is concluded that ADP induced release reaction can occur in heparinized PRP but that it is enhanced by reducing the concentration of extracellular ionised calcium.

Evidence for Separate Mechanisms of Induction of the Platelet Release Reaction by Collagen and Adrenaline

1975 ◽  
Author(s):  
O. Tangen ◽  
S. Bygdeman
Keyword(s):  
Platelet Aggregation ◽  
Blood Clotting ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Human Platelet Aggregation ◽  
Small Doses ◽  
Platelet Release ◽  
Induced Aggregation

The effect of some selected inhibitors of platelet release reaction and blood clotting on collagen- and adrenaline-induced human platelet aggregation was investigated by means of the turbidimetric method according to Born. Acetylsalicylic acid (ASA) inhibited both collagen- and adrenaline-induced platelet aggregation in citrated platelet rich plasma (PRP). Addition of sufficient amounts of Ca++ to give concentrations similar to those in native blood suppressed the inhibition by small doses of ASA (5–10 μg/ml) on collagen-induced aggregation and the second phase of adrenaline-induced aggregation. Higher concentrations of ASA (13–30 μg/ml) could partly overcome this effect of Ca++. Heparin, which had no effect on primary adenosine diphosphate (ADP)-induced aggregation, inhibited platelet aggregation induced by collagen. In contrast, both the first and second phase of adrenaline-induced aggregation was markedly potentiated by heparin. Dextran sulphate had effects basically similar to heparin, Nicotinic acid inhibited collagen-induced aggregation, but had no effect on the second phase of adrenaline-induced aggregation. These results indicate that the platelet release reaction induced by collagen and adrenaline is mediated via separate receptors or reaction pathways.

The effects of an ASA-like hydroperoxide compound on adenosine diphosphate induced platelet aggregation

1984 ◽  
Vol 62 (3) ◽  
pp. 338-340
Author(s):  
J. J. F. Killackey ◽  
B. A. Killackey ◽  
I. Cerskus ◽  
R. B. Philp
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Pharmacological Property ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Human Platelet Aggregation ◽  
Second Phases ◽  
Induced Aggregation

A hydroperoxide compound structurally related to acetylsalicylic acid, 3-hydroperoxy-3-methylphthalide, inhibits both the first and second phases of adenosine diphosphate induced, biphasic, human platelet aggregation. This occurs over the same concentration range (0.05–0.5 mM) that acetylsalicylic acid inhibits second phase aggregation and the release reaction only. The complete inhibition of adenosine diphosphate induced aggregation is a unique pharmacological property for an acetylsalicylic-acid-like compound.

The Effect of Neuraminidase on Platelet Aggregation Induced by ADP, Norepinephrine, Collagen or Serotonin

1972 ◽  
Vol 28 (02) ◽  
pp. 221-227 ◽  
Author(s):  
James W. Davis ◽  
Kenneth T. N. Yue ◽  
Phyllis E. Phillips
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Acetylneuraminic Acid ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
Second Phases ◽  
Induced Aggregation

SummaryIncubation of human platelet-rich plasma (PRP) with neuraminidase enhanced platelet aggregation induced by adenosine diphosphate (ADP), norepinephrine, collagen or serotonin. Both first and second phases of ADP- and norepinephrine -induced aggregation were enhanced. In two plasmas a second phase of ADP-induced aggregation occurred after incubation with neuraminidase, but not in the control preparations. In one plasma a second phase of serotonin-induced platelet aggregation occurred after incubation with neuraminidase. The incubation of PRP with exogenous N-acetylneuraminic acid (a product of the action of neuraminidase) had no effect on platelet aggregation. A possible explanation of the observed enhancement of platelet aggregation by neuraminidase is that the enzyme may have released sialic acid from platelet membranes and thereby reduced their net negative surface charge.

PLATELET AGGREGATION DYNAMICS TO ADENOSINE DIPHOSPHATE IN NON-STIRRED SUSPENSIONS: LONG-RANGEINTERACTIONS FOR HUMAN, BUT NOT RABBIT, PLATELETS

1987 ◽  
Author(s):  
K Longmire ◽  
M M Frojmovic
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Linear Regression Analysis ◽  
Time Lag ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Dense Granule ◽  
Second Phase ◽  
Particle Count ◽  
Induced Aggregation

The simplest experimental approach for a theoretical description of platelet aggregation is based on kinetics of early multiplet formation (‹4 platelets per aggregate)occurring with diffusion-dependent particle collisions (no flow). The Smoluchowski theory was used to calculate collision efficiencies, αβ, from a linear plot of platelet particle count (Nt)−1 vs time (t) following addition of adenosine diphosphate (ADP) to citrated platelet-rich-plasma (PRP) for 7 human (H) and 2 rabbit (R) donors. A 0.1 ml sample of PRP was stirred with ADP for 0.5s, then immediately transferred to a 37°C bath for no-stir (diffusion) studies or further stirred with ADP for stir-induced aggregation studies. Samples were fixed with 0.5 ml 0.8% glutaraldehyde with particle count (Nt) determined with a resistive counter and % aggregation (PA) computed (reproducibility/sensitivity ‹ 5%). For stir conditions, R platelets were as sensitive and as rapidly aggregated by ADP (2-10 μM) as H platelets, with ∼ 1 s time lag for onset of PA. However, for no-stir conditions, linear regression analysis of data for ADP (5-10 μM) induced PA for H platelets for 0-30 s gave αβ = 7.5±4.6 (r = 0.9±0.05). Analysis at longer “diffusion” times showed a second phase (60-300 s) in some H donors with aB = 0.5±0.4 (4/9 donors), while R platelets showed only 1 phase with αβ = 0.65±0.15 (0-60 to 0-900 s) (r = 0.8±0.1). The ADP sensitivity ([ADP]½ corresponding to 50% of maximal changes) for the abnormally rapid PA in no stir H PRP for early times, measured over 0.4-100 μM range, was found to be ∼9 μM (5-17 μM range) and 3.5 μM (3-10 μM) for measurements respectively at 5-10 and 20-30s; these values were ∼ 3-8 × greater than lADPji measured for stirred suspensions for rate/extent of PA or rate of turbidometrically-measured macroaggregation (TA), while › [ADP] threshold for secondary aggregation in TA (10 H donors). These abnormally large aB values and their ADP sensitivity observed for human platelets are consistent with long-range interactions mediated by“chemotactic” agents released from the cells but distinct from normal dense granule release requiring macroaggregation, or by as yet uncharacterized membrane or polymetric bridges.

scholarly journals Zinc-induced platelet aggregation is mediated by the fibrinogen receptor and is not accompanied by release or by thromboxane synthesis

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 213-219 ◽  
Author(s):  
P Heyns A du ◽  
A Eldor ◽  
R Yarom ◽  
G Marx
Keyword(s):  
Platelet Aggregation ◽  
Dense Body ◽  
Platelet Rich Plasma ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Creatine Phosphate ◽  
Calcium Flux ◽  
Fibrinogen Receptor ◽  
Induced Aggregation

Abstract We demonstrate that zinc (0.1 to 0.3 mmol/L) induces aggregation of washed platelet suspensions. Higher concentrations (1 to 3 mmol/L) of zinc were needed to aggregate platelets in platelet-rich plasma obtained from blood anticoagulated with low-molecular-weight heparin, probably due to the binding of zinc to the plasma proteins. Zinc- induced aggregation of normal washed platelets required added fibrinogen and no aggregation occurred with thrombasthenic platelets or with normal platelets pretreated with a monoclonal antibody (10E5) that blocks the platelet fibrinogen receptor. These data indicate that the platelet membrane fibrinogen receptor-glycoproteins IIb and IIIa mediate the effect of zinc. Zinc-induced aggregation was blocked by the agent TMB-8, which interferes with the internal calcium flux, and by prostacyclin, which elevates platelet cyclic adenosine monophosphate levels. Zinc-induced aggregation was not accompanied by thromboxane synthesis or by the secretion of dense-body serotonin and was not affected by preexposure of platelets to acetylsalicylic acid. Experiments with creatine phosphate/creatine phosphokinase showed that the zinc effect on platelets was independent of extracellular adenosine diphosphate (ADP). Zinc had an additive effect when platelet aggregation was stimulated with subthreshhold concentrations of collagen or ADP. Together with the known effects of nutritional zinc on in vivo bleeding, on platelet aggregation, and on lipid metabolism, the results suggest that zinc may have an important bearing on normal hemostasis, thrombosis, and atherosclerosis.

scholarly journals Abnormalities of factor VIII and platelet aggregation--use of ristocetin in diagnosing the von Willebrand syndrome

Blood ◽  
1975 ◽  
Vol 45 (3) ◽  
pp. 403-412 ◽  
Author(s):  
HJ Weiss
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Low Concentrations ◽  
Platelet Defects ◽  
Von Willebrand ◽  
Induced Aggregation

Ristocetin was used to study platelet aggregation in platelet-rich plasma and to assay the von Willebrand factor activity of factor VIII (VIII-VWF). Ristocetin-induced platelet aggregation (RIPA) was decreased in 13 of 18 patients with von Willebrand's disease (VWD) who had decreased plasma levels of VIII-VWF. The five patients with normal RIPA appeared to have mild VWD but did not constitute a separate subclass. RIPA was also abnormal in some patients with intrinsic platelet defects, but in no case was the defect corrected by normal plasma. The latter type of correction appears to be specific for VWD. Aspirin ingestion inhibited the second phase of RIPA (at low concentrations of ristocetin only) but did not affect the initial phase of aggregation or the level of VIII-VWF. We also studied a group of patients who had both abnormalities of the factor VIII complex and intrinsic platelet defects, such as impaired collagen-induced aggregation, as well. The findings in these patients and in those with typical von Willebrand's disease appear to comprise a spectrum of disorders (the von Willebrand syndrome) in which some abnormality of the factor VIII complex is associated with impaired platelet function. At present, ristocetin would appear to be a useful reagent for evaluating patients with bleeding disorders and for studying patients with the von Willebrand syndrome.

Inhibition of ADP-Induced Platelet Aggregation by Adenosine Tetraphosphate

1976 ◽  
Vol 36 (02) ◽  
pp. 388-391 ◽  
Author(s):  
Margaret J. Harrison ◽  
R Brossmer
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Action ◽  
Platelet Rich Plasma ◽  
Release Reaction ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryIn contrast to previous reports, highly purified adenosine tetraphosphate (AP4) does not induce the aggregation of platelets but inhibits the aggregation and release reaction in platelet-rich plasma promoted by ADP. The inhibitory action of AP4 on the aggregation by ADP is compared with that of AMP and ATP. The data presented suggest a competitive manner of inhibition of the ADP-induced aggregation by AP4.

Second Phase Platelet Aggregation Induced by Adenosine Diphosphate in Patients with Cerebral Vascular Disease and in Control Subjects

1970 ◽  
Vol 23 (01) ◽  
pp. 159-169 ◽  
Author(s):  
G Danta
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Vascular Disease ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Cerebral Vascular Disease ◽  
The Mean ◽  
Phase Platelet ◽  
Cerebral Vascular

SummaryAdenosine diphosphate-induced second phase platelet aggregation was studied in 70 patients with established cerebral vascular disease, 27 patients with chronic cerebral vascular disease taking dipyridamole, and 53 control subjects. The appearances of aggregation graphs relating changes in optical density in platelet-rich plasma to time after addition of adenosine diphosphate are described. An intermediate rate change in optical density was observed between first and second phase aggregation.Induction of second phase aggregation depends on the concentration of adenosine diphosphate and the platelet count of the plasma. Individual rseponses vary greatly, and there is appreciable variability in repeated estimations, but in the same plasma responses to adenosine diphosphate are accurately reproducible.In both patients and controls the mean logarithm of the adenosine diphosphate concentration that just induces second phase aggregation is inversely proportional to the mean platelet count of platelet-rich plasma. At all platelet concentrations studied, the smallest concentration of adenosine diphosphate that brought about second phase aggregation was significantly less in the patients than in controls. There was no significant correlation between the means of the two variables in patients taking dipyridamole. The findings in this group of patients accord with the assumption that dipyridamole favourably affects the abnormal reaction of platelets to adenosine diphosphate in some of the patients with cerebral vascular disease.

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.

scholarly journals Secretory mechanisms. Behaviour of adenine nucleotides during the platelet release reaction induced by adenosine diphosphate and adrenaline

1972 ◽  
Vol 129 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Holm Holmsen ◽  
H. James Day ◽  
Carol A. Setkowsky
Keyword(s):  
Adenine Nucleotides ◽  
Specific Radioactivity ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Concentration Time ◽  
Aggregation Pattern ◽  
Induced Aggregation ◽  
Phasic Release

1. Platelets containing adenine nucleotides labelled with3H and14C in vitro were aggregated biphasically with ADP and adrenaline. Amounts of ATP and ADP as well as the radioactivity of ATP, ADP, AMP, IMP, hypoxanthine and adenine were determined in platelets and plasma at different stages of aggregation. 2. ATP and ADP were released during the second aggregation phase and had a low specific radioactivity compared with the ATP and ADP retained by the cells. The specific radioactivity of intracellular nucleotides increased during release. The parameters observed with ADP and adrenaline as release inducers were the same as for collagen and thrombin. 3. Release induced by all four inducers was accompanied by conversion of cellular [3H]ATP into extracellular [3H]-hypoxanthine. By variation of temperature, inducer concentration, time after blood withdrawal and use of acetylsalicylic acid, the aggregation pattern caused by adrenaline and ADP could be made mono- or bi-phasic. Release or second-phase aggregation was intimately connected with the ATP–hypoxanthine conversion, whereas first phase aggregation was not. 4. The [3H]ATP–hypoxanthine conversion started immediately after ADP addition. With adrenaline it usually started with the appearance of the second aggregation phase. The conversion was present during first phase of ADP-induced aggregation only if a second phase were to follow. 5. When secondary aggregation took place while radioactive adenine was being taken up by the platelets, increased formation of labelled hypoxanthine still occurred, but there was either no change or an increase in the concentration of labelled ATP. 6. Biphasically aggregated platelets converted [3H]adenine more rapidly into [3H]-ATP and -hypoxanthine than non-aggregated platelets. Addition of [3H]adenine at different stages of biphasic aggregation showed that more [3H]hypoxanthine was formed during than after the release step. 7. We conclude that ADP and adrenaline, like thrombin and collagen, cause extrusion of non-metabolic granula-located platelet adenine nucleotides. During release metabolic ATP breaks down to hypoxanthine, and this process might reflect an ATP-requiring part of the release reaction.

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