scholarly journals METABOLISM AND CHEMILUMINESCENT ACTIVITY OF NEUTROPHILIC GRANULOCYTES IN PATIENTS WITH DIFFERENT SENSITIVITY TO ACETYLSALICYLIC ACID IN ACUTE CORONARY SYNDROME

2017 ◽  
Vol 8 (3) ◽  
pp. 10-17
Author(s):  
I Yu Grinshtein ◽  
A A Savchenko ◽  
Yu I Grinshtein ◽  
I I Gvozdev
Keyword(s):  
Acute Coronary Syndrome ◽  
Acetylsalicylic Acid ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Adenosine Diphosphate ◽  
Pentose Phosphate ◽  
Neutrophilic Granulocytes ◽  
Active Forms Of Oxygen ◽  
Coronary Syndrome

Objective: to study the features of the chemiluminescent state and the activity of NAD (P) -depen- dent dehydrogenases in neutrophilic granulocytes of blood in patients with different sensitivity to acetylsalicylic acid (ACA) in acute coronary syndrome (ACS).Materials and methods: The study included 53 patients with ACS. Evaluation of resistance or sensitivity to ASA was performed in vitro by incubating platelet-rich plasma with adenosine diphosphate and ASA to determine the level of aggregation. The state of respiratory explosion of neutrophils was investigated by the method of chemiluminescence. The activity of enzymes in neutrophils was studied by the bioluminescent method.Results of the study: In patients with ACS-resistant ACS, the rate of synthesis of primary and secondary active forms of oxygen was reduced, and the index of luminol-dependent activation of neutrophils was reduced. The intensity of substrate stimulation of glycolysis and oxidation of glucose by the pentose phosphate pathway is increased.Conclusion: With resistance to ASA in patients with ACS, there are abnormalities in the metabolism and functional activity of neutrophils, which is of interest in studying the intercellular relationships of thrombus formation.

Discovery, Engineering and Pre-Clinical Evaluation of an Anti-vWF A1 Domain Aptamer.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3930-3930
Author(s):  
John L. Diener ◽  
H.A. Daniel Lagasse ◽  
Madaline Gilbert ◽  
Patricia Merlino ◽  
Jason Killough ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Shear Force ◽  
In Vitro Selection ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Dna Aptamer ◽  
Coronary Syndrome ◽  
Limit Blood Flow ◽  
A1 Domain

Abstract Following coronary artery damage, von Willebrand Factor (vWF) multimers adhere to exposed collagen via the vWF A3 domain. Platelets passing through damaged vessels under the conditions of high shear force associated with stenosed arteries will adhere to the vWF A1 domain via GPIb receptors. This initial platelet binding event triggers the formation of a thrombus that can limit blood flow to the myocardium and produce the symptoms of acute coronary syndrome (ACS). Through in vitro selection (SELEX) and subsequent lead optimization, we have generated a nuclease-resistant DNA aptamer that binds to the vWF A1 domain with high affinity. The anti-vWF aptamer inhibits both botrocetin-induced platelet aggregation of platelet rich plasma and shear force-induced platelet aggregation in citrated whole blood. Continuous intravenous infusion of the aptamer in cynomolgus macaques is able to effectively inhibit thrombus formation induced by electrical injury to the carotid artery. Modest effects on template bleeding are observed with the vWF-specific aptamer relative to anti-GPIIb/IIIa therapy. Based upon these results, this aptamer is an excellent candidate for treatment of ACS.

In Vitro Reversal of the Anti-Aggregant Effect of Ticagrelor Using Untreated Platelets

2018 ◽  
Vol 118 (11) ◽  
pp. 1895-1901 ◽  
Author(s):  
Paul Kruger ◽  
Jack Hirsh ◽  
Vinai Bhagirath ◽  
Ke Xu ◽  
Brian Dale ◽  
...  
Keyword(s):  
Platelet Transfusion ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Coronary Syndrome ◽  
Coronary Artery Stent ◽  
Anti Platelet Agent ◽  
Light Transmission Aggregometry ◽  
Optimal Quantity

Background Ticagrelor is an anti-platelet agent that is indicated for prevention of thrombosis after acute coronary syndrome or intra-coronary artery stent implantation, but it increases the risk of bleeding. Platelet transfusion has the potential to treat or prevent bleeding in patients taking ticagrelor, but the optimal quantity of platelets and timing of administration have not been fully defined. Methods and Results Ten healthy subjects took ticagrelor in combination with acetylsalicylic acid for 5 days, and had blood collected prior to treatment and at 2, 10, 24, 48, 72 and 96 hours after the last doses. The potential of platelet transfusion to prevent or reverse bleeding was evaluated by mixing subject and donor platelet-rich plasma in vitro in nine different proportions, and measuring adenosine diphosphate-mediated aggregation by light transmission aggregometry. Spontaneous offset of the anti-aggregant effect of ticagrelor occurred gradually and was complete at 72 hours after the last dose. The addition of donor platelets enhanced the recovery. The addition of the equivalent of six apheresis platelet units produced a 50% relative reversal at 10 hours, and > 90% reversal at 24 hours. Conclusion Donor platelets enhance reversal of the anti-aggregant effect of ticagrelor in vitro. Donor platelets given in clinically relevant amounts partially reversed ticagrelor at 10 hours after the last dose, and almost fully reversed ticagrelor at 24 hours. The results inform on the potential to reverse ticagrelor in patients who develop bleeding or require emergency surgery.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Unique coronary vasodilator induction by leukotriene D4

1985 ◽  
Vol 249 (3) ◽  
pp. H698-H702 ◽  
Author(s):  
D. Ezra ◽  
G. Feuerstein ◽  
J. F. Czaja ◽  
F. R. Laurindo ◽  
C. K. Finton ◽  
...  
Keyword(s):  
Coronary Flow ◽  
Platelet Rich Plasma ◽  
Platelet Activating Factor ◽  
Adenosine Diphosphate ◽  
Coronary Vein ◽  
Marked Rise ◽  
Leukotriene D4 ◽  
Coronary Vasodilator ◽  
Myocardial Area

Coronary blood flow (CBF) and myocardial contractility decrease markedly in response to intracoronary administration of leukotriene D4 (LTD4). With steady infusion, however, both CBF and contractility escape, approaching preinfusion values despite ongoing LTD4 administration. To clarify the mechanism of this escape, we reinfused plasma from the coronary vein draining the myocardial area receiving LTD4. Introducing this plasma into a coronary artery caused a marked rise in coronary flow for the duration of the plasma infusion. Coronary flow reduction with vasopressin or mechanical occlusion matching that caused by LTD4 failed to elicit vasodilator production. Thus a unique coronary vasodilator factor is induced by LTD4. Whole blood or platelet-rich plasma incubated with LTD4 in vitro produced the same pattern of coronary dilation on intracoronary infusion; LTD4 incubation with platelet-poor plasma failed to elicit a vasodilation. The vasodilator factor is stable and is not potassium, a prostaglandin, catecholamine, histamine, serotonin, adenosine, adenosine diphosphate, or platelet-activating factor. Production of this leukotriene-induced vasodilator factor may account for the escape from LTD4-induced coronary constriction.

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