scholarly journals Anti-Heparin and Platelet Aggregation Activities of Polyamino Acids

1977 ◽  
Author(s):  
Jawed Fareed ◽  
Harry L. Messmore ◽  
John U. Balis ◽  
Rogelio Moncada
Keyword(s):  
Platelet Aggregation ◽  
Contrast Media ◽  
Platelet Rich Plasma ◽  
Anticoagulant Activity ◽  
Lag Time ◽  
Thrombin Time ◽  
Irreversible Aggregation ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Biphasic Process

An earlier report from this laboratory has described the antagonism of the anticoagulant effect of heparin by certain basic polyamino acids. Of the numerous polyamino acids tested, only basic polyarnino acids such as poly-L-lysine (MW 85,000) and poly-L-omithine (MW 120,000) effectively neutralized heparinized plasma (1 u/ml) in concentrations less than 10 μg/ml. Addition of these two polyamino acids in quantities up to 50 μg/ml citrated plasma, significantly shortened the thrombin time. Poly-L-proline (MW 19,000), poly-L-histidine (MW 16,000) and poly-L-lysine (MW 85,000) possessed weak anti-heparin action. These polyamino acids also neutralized the anticoagulant activity of hirudin and polyanetholsulfonic acid in varying degrees. The effects of polyamino acids on platelet aggregation was also tested. Of the 15 basic polyamino acids tested, only poly-L-α-omithine was found to induce aggregation of platelets. Polyornithine in the amounts of 50.0, 25.0 and 12.5 μg/ml to platelet rich plasma caused a 65, 45 and 30% change in transmittance, respectively. The polyornithine induced aggregation (PIA) of platelets was only partially blocked by acetylsalicylic acid. Contrast media (6.0 mg/ml) used in diagnostic radiology and meglumine (5 mg/ml) totally blocked the PIA. The PIA of platelets was found to be a biphasic process, an initial lag time of 30 seconds, after which irreversible aggregation was observed. These studies suggest that basic polyamino acids may be used clinically to antagonize overheparinization; in addition, polyornithine may prove useful in the diagnosis of platelet function defects.

The Effect of Molecular Iodine on Platelet Aggregation in Vitro

1974 ◽  
Vol 31 (01) ◽  
pp. 160-171 ◽  
Author(s):  
Kiyomi Kikugawa
Keyword(s):  
Platelet Aggregation ◽  
Reduced Glutathione ◽  
Platelet Rich Plasma ◽  
Molecular Iodine ◽  
Sulfhydryl Groups ◽  
Rabbit Platelet ◽  
Irreversible Aggregation ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryWhen rabbit platelet-rich plasma was treated with 1-2 mM molecular iodine, marked irreversible aggregation of platelets was observed. The aggregation was characterized by inhibition by 1 mM reduced glutathione, acceleration by 0.1 mM NEM, and no interference with EDTA and adenosine which are powerful inhibitors of aggregation induced by ADP. Molecular iodine at a concentration of 0.5 mM did not induce aggregation and caused more than 60% inhibition of ADP- and collagen-induced aggregation. These findings indicated that the aggregation by molecular iodine was in quite different mechanisms from those by other aggregating agents such as ADP, and suggested that platelet aggregation by molecular iodine and ADP was greatly regulated by sulfhydryl groups.

scholarly journals Both Complement- and Fibrinogen-Dependent Mechanisms Contribute to Platelet Aggregation Mediated by Staphylococcus aureus Clumping Factor B

2007 ◽  
Vol 75 (7) ◽  
pp. 3335-3343 ◽  
Author(s):  
Helen Miajlovic ◽  
Anthony Loughman ◽  
Marian Brennan ◽  
Dermot Cox ◽  
Timothy J. Foster
Keyword(s):  
Staphylococcus Aureus ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Lag Time ◽  
Dependent Manner ◽  
Wild Type ◽  
Factor B ◽  
Fibrinogen Binding ◽  
Aggregation Of Platelets ◽  
Dependent Mechanism

ABSTRACT Staphylococcus aureus can stimulate activation and aggregation of platelets, which are thought to be factors in the development of infective endocarditis. Previous studies have identified clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as potent platelet aggregators. These proteins are able to stimulate rapid platelet aggregation by either a fibrinogen- or a fibronectin-dependent process which also requires antibodies specific to each protein. Slower aggregation has been seen in other systems where specific fibrinogen binding ligands are absent and platelet aggregation is mediated by complement and specific antibodies. Bacteria expressing ClfB aggregate platelets with a longer lag time than ClfA or FnBPA and FnBPB. In order to investigate whether ClfB causes platelet aggregation in a complement- or fibrinogen-dependent manner, a non-fibrinogen-binding mutant of ClfB (ClfB Q235A) was constructed. Lactococcus lactis expressing ClfB Q235A was able to stimulate platelet aggregation in platelet-rich plasma without a significant increase in lag time. The requirements for platelet aggregation were investigated using gel-filtered platelets. Fibrinogen and specific anti-ClfB antibodies were found to be sufficient to allow platelet aggregation mediated by the wild-type ClfB protein. It seems that ClfB causes platelet aggregation by a fibrinogen-dependent mechanism. The non-fibrinogen-binding ClfB mutant was unable to stimulate platelet aggregation under these conditions. However, bacteria expressing ClfB Q235A caused platelet aggregation in a complement-dependent manner which required specific anti-ClfB antibodies.

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.

Heparin-Induced Thrombocytopenia Platelet Aggregation Studies in the Presence of Heparin Fractions or Semi-Synthetic Analogues of Various Molecular Weights and Anticoagulant Activities

1986 ◽  
Vol 55 (01) ◽  
pp. 090-093 ◽  
Author(s):  
D Blockmans ◽  
H Bounameaux ◽  
J Vermylen ◽  
M Verstraete
Keyword(s):  
Molecular Weight ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Anticoagulant Activity ◽  
Lag Phase ◽  
Synthetic Analogues ◽  
Heparin Induced Thrombocytopenia ◽  
Molecular Weights ◽  
Induced Aggregation

SummaryOne case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions.The patient’s isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient’s platelet poor plasma (PPP).Furthermore, addition of patient’s PPP to control platelets led to heparin-induced aggregation.The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine.It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.

Effects of Ticlopidine and Indobufen on Platelet Aggregation Induced by A23187 and Adrenaline in the Presence of Different Anticoagulants

1989 ◽  
Vol 17 (6) ◽  
pp. 514-520 ◽  
Author(s):  
C. Cimminiello ◽  
M. Milani ◽  
T. Uberti ◽  
G. Arpaia ◽  
G. Bonfardeci
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Sodium Citrate ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
Ionophore A23187 ◽  
Tyrode Solution ◽  
Low Levels ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

As Ca2+ is known to play a fundamental role in platelet function, the effect of combining two platelet aggregating agents (adrenaline and the ionophore A23187) with different effects on Ca2+ was studied at levels subthreshold for aggregation using platelet-rich plasma from eight atherosclerotic patients. Adrenaline lowered the A23187 threshold required to induce aggregation. The effects of treating patients with the antiplatelet agents, indobufen and ticlopidine, on A23187 and adrenaline induced aggregation of platelets prepared in hirudin or sodium citrate was also evaluated. Aggregation was also studied using platelets resuspended in Ca2+-free and Ca2+-enriched Tyrode solution. Before treatment hirudin treated platelet-rich plasma, which has physiological extraplatelet Ca2+ levels, was more sensitive to A23187 and adrenaline than was citrated platelet-rich plasma, which has suppressed Ca2+ levels. Ticlopidine significantly raised the concentration of A23187 required to induce aggregation in citrated but not hirudin treated platelet-rich plasma. Indobufen did not significantly affect A23187 induced aggregation. Ticlopidine acts by inhibiting the glycoprotein IIb – IIIa complex on the platelet membranes. Low levels of extracellular Ca2+ and ticlopidine may act synergistically to reduce the aggregatory response of stimulated platelets.

Effect Of Ionic And Non-Ionic Contrast Media On Components Of Coagulation And Complement Pathways

1981 ◽  
Author(s):  
R Moncada ◽  
Z Parvez ◽  
J Fareed ◽  
P Agrawal ◽  
H L Messmore
Keyword(s):  
Contrast Media ◽  
Protein C ◽  
Thrombin Time ◽  
Complement Protein ◽  
Ionic Contrast ◽  
Anticoagulant Drugs ◽  
Coagulation Tests ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Ionic Forms

The effects of a recently developed non-ionic contrast media (CM) P-297 and two ionic forms Ioxigalic acid and Iothalamic acid (Laboratoire Guerbet, Paris, France) were studied on coagulation and complement systems, and their interactions with anticoagulant drugs. In coagulation studies, a 1:10 mixture of P-297 (10%) in human plasma (both normal and abnormal) was prepared and prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) were determined. Similar studies were performed with Ioxigalic acid (10%), and Iothalamic acid (10%). Separate pools of (10) individual plasmas representing disorders of intrinsic and extrinsic pathways of coagulation were similarly mixed with CM and the clotting times were determined. In all of these experiments, there was only a slight increase in TT whereas PTs and PTTs were not affected. Of the three CM tested, P-297 (10%) showed considerably less anticoagulant action than ioxigalic and iothalamic acids. All the CM exhibited a synergistic effect with 0.2u/ml heparin and greatly prolonged (>100 secs.) all coagulation tests. All of the three CM at (10 mg/ml) failed to produce any significant blockade of thrombin-induced aggregation of platelets, however at 40-80mg/ ml level did block thrombin-induced aggregation. In complement activation studies, serum C-3 levels in pre-and post-CM incubation samples were determined by a rocket technique. No consumption of the complement protein C-3 or split products of C-3 were seen in counter immunoelectrophoresis. These studies indicate that P-297 possesses mild anticoagulant and complement activating actions, and seems relatively safer than other ionic forms of CM. Furthermore, our studies suggest that non-ionic contrast agents produce minimal effects on coagulation and complement systems and can be used without much risk to patients with pre-existing coagulation and/or complement disorders.

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.

scholarly journals Effect of prostaglandin E1 alone and in combination with theophylline or aspirin on collagen-induced platelet aggregation and on platelet nucleotides including adenosine 3′:5′-cyclic monophosphate

1970 ◽  
Vol 120 (4) ◽  
pp. 709-718 ◽  
Author(s):  
G. Ball ◽  
G. G. Brereton ◽  
Mary Fulwood ◽  
D. M. Ireland ◽  
Patricia Yates
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Prostaglandin E1 ◽  
Platelet Rich Plasma ◽  
Dependent Manner ◽  
Intracellular Changes ◽  
Induced Aggregation ◽  
Dose Dependent ◽  
Aggregation Of Platelets ◽  
Collagen Treatment

1. Human platelet nucleotides were labelled by incubating platelet-rich plasma with [U-14C]adenine. With such platelets, the effects of prostaglandin E1, theophylline and aspirin were determined on collagen-induced platelet aggregation and release of platelet ATP and ADP. Intracellular changes of platelet radioactive nucleotides, particularly 3′:5′-cyclic AMP, were also determined both with and without collagen treatment. 2. Prostaglandin E1, theophylline and aspirin inhibited collagen-induced aggregation of platelets in a dose-dependent manner. Collagen-induced release of ATP and ADP and breakdown of radioactive ATP were also inhibited in a dose-dependent manner. 3. Prostaglandin E1 stimulated the formation of platelet radioactive 3′:5′-cyclic AMP in a dose-dependent manner. With a given dose of prostaglandin E1, maximum formation of radioactive 3′:5′-cyclic AMP occurred by 10–30s and thereafter the concentrations declined. The degree of inhibition of aggregation produced by prostaglandin E1, however, increased with its time of incubation in platelet-rich plasma before addition of collagen, so that there was an inverse relationship between the radioactive 3′:5′-cyclic AMP concentration measured at the time of collagen addition and the subsequent degree of inhibition of aggregation obtained. 4. Neither theophylline nor aspirin at a concentration in platelet-rich plasma of 1.7mm altered platelet radioactive 3′:5′-cyclic AMP contents. In the presence of prostaglandin E1, theophylline increased the concentration of radioactive 3′:5′-cyclic AMP over that noted with prostaglandin E1 alone, but aspirin did not. 5. Mixtures of prostaglandin E1 and theophylline had a synergistic effect on inhibition of platelet aggregation. The same was true to a lesser extent with mixtures of prostaglandin E1 and aspirin. Such mixtures also inhibited collagen-induced release of platelet ATP and ADP and breakdown of platelet radioactive ATP. 6. Certain concentrations of either theophylline or aspirin and mixtures of small concentrations of prostaglandin E1 with either theophylline or aspirin caused little or no increase of radioactive 3′:5′-cyclic AMP at the time of collagen addition, but inhibited aggregation to a marked degree, whereas higher concentrations of prostaglandin E1 alone caused a much greater increase of radioactive 3′:5′-cyclic AMP at the time of collagen addition but inhibited aggregation to a lesser extent. With these compounds there does not appear to be a correlation between these parameters.

scholarly journals Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 1027-1031 ◽  
Author(s):  
AJ Marcus ◽  
LB Safier ◽  
HL Ullman ◽  
KT Wong ◽  
MJ Broekman ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Initial Phase ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Strong Stimulus ◽  
Adp Release ◽  
Irreversible Aggregation ◽  
Induced Aggregation

Abstract AGEPC (PAF), at 1.9 x 10(-8) M or higher, induced concentration- dependent aggregation and release in human platelet-rich plasma. Comparative studies with arachidonate, collagen, ionophore, and ADP suggested that AGEPC was a strong stimulus for platelet aggregation and probably a moderate agonist for release, as well as a relatively weak inducer of TXA2 production. The initial phase of AGEPC-induced aggregation was independent of ADP release and TXA2 formation, since it was not inhibited by ASA, apyrase, or CP/CPK. Whereas irreversible aggregation always required ADP release, TXA2 formation was not essential in each instance. Thus, in several experiments, full aggregation responses took place in AGEPC-stimulated platelets that had been pretreated with ASA. AGEPC-induced release of 5-HT, beta - thromboglobulin and PF-4 occurred in parallel and were inhibited by both apyrase and ASA. Washed human platelets did not respond to exogenous AGEPC in the absence of ADP and did not appear to generate significant quantities of AGEPC upon stimulation with thrombin or ionophore.

ATP- and ADP-Induced Rat Platelet Aggregation: Significance of Plasma in ATP-Induced Aggregation

1979 ◽  
Vol 42 (05) ◽  
pp. 1580-1588 ◽  
Author(s):  
Ethan J Haskel ◽  
Kailash C Agarwal ◽  
Robert E Parks
Keyword(s):  
Creatine Kinase ◽  
Platelet Aggregation ◽  
Human Plasma ◽  
Platelet Rich Plasma ◽  
Creatine Phosphate ◽  
Rat Plasma ◽  
Human Platelets ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Rat Platelets

SummaryATP caused platelet aggregation in rat platelet-rich plasma (PRP) but in contrast strongly inhibited ADP-induced human platelet aggregation. ADP-induced aggregation of rat platelets suspended in human plasma was strongly inhibited by ATP, whereas human platelets in rat plasma were aggregated by ADP. The ATP analog β,γ-methylene ATP which is not dephosphorylated did not induce aggregation in rat PRP. Adenosine, AMP, 2- chloroadenosine, α,β-methylene ADP and β,γ-methylene ATP each inhibited ATP-induced aggregation of platelets in rat PRP to a similar extent as ADP-induced aggregation. A solution containing creatine kinase and creatine phosphate (which converts ADP to ATP) rapidly reversed both ADP- and ATP-induced aggregation in rat PRP; preincubation with this solution completely inhibited rat platelet aggregation induced by both ADP and ATP. Adenosine-8-14C-triphosphate ([14C]-ATP) conversion to [14C]-ADP was about five-fold faster in rat plasma than in human plasma. Addition of creatine phosphate to rat PRP strongly inhibited ATP-induced aggregation, while creatine or creatine kinase slightly potentiated aggregation by ATP. Creatine phosphate, creatine, or creatine kinase individually had minimal and varying effects on ADP-induced rat platelet aggregation. These results suggest that the observed phenomenon of ATP-induced aggregation in rat PRP is caused by a higher activity of creatine kinase in rat plasma than in human plasma, which converts the added ATP to ADP, a potent aggregator.

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