scholarly journals Platelet Reactivity Is Independent of Left Atrial Wall Deformation in Patients with Atrial Fibrillation

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Nathan Procter ◽  
Vincent Goh ◽  
Gnanadevan Mahadevan ◽  
Simon Stewart ◽  
John Horowitz
Keyword(s):  
Left Atrial ◽  
Platelet Reactivity ◽  
Blood Stasis ◽  
Inhibitory Response ◽  
No Donor ◽  
Interacting Protein ◽  
Impedance Aggregometry ◽  
Mediators Of Inflammation ◽  
Wall Deformation ◽  
Induced Aggregation

It has been documented recently that left atrial (LA) deformation in AF patients (while in AF) is predictive of subsequent stroke risk. Additionally, diminished LA deformation during AF correlates with the presence of LA blood stasis. Given that endothelial function is dependent on laminar blood flow, the present study sought to investigate the effect of diminished LA deformation (during AF) on platelet reactivity and inflammation in AF patients. Patients (n=17) hospitalised with AF underwent echocardiography (while in AF) for determination of peak positive LA strain (LASp). Whole blood impedance aggregometry was used to measure extent of ADP-induced aggregation and subsequent inhibitory response to the nitric oxide (NO) donor, sodium nitroprusside. Platelet thioredoxin-interacting protein (Txnip) content was determined by immunohistochemistry. LASp tended (p=0.078) to vary inversely with CHA2DS2VASc scores. However, mediators of inflammation (C-reactive protein, Txnip) did not correlate significantly with LASp nor did extent of ADP-induced platelet aggregation or platelet NO response. These results suggest that the thrombogenic risk associated with LA stasis is independent of secondary effects on platelet aggregability or inflammation.

scholarly journals Role of Dipyrone in the High On-Treatment Platelet Reactivity amongst Acetylsalicylic Acid-Treated Patients Undergoing Peripheral Artery Revascularisation

2018 ◽  
Vol 27 (4) ◽  
pp. 356-361 ◽  
Author(s):  
Jan Hartinger ◽  
Robert Novotny ◽  
Jana Bilkova ◽  
Tomas Kvasnicka ◽  
Petr Mitas ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Peripheral Artery ◽  
Primary Resistance ◽  
Impedance Aggregometry ◽  
Number Of Patients ◽  
Light Transmission Aggregometry ◽  
Daily Dose ◽  
Induced Aggregation

Objective: To evaluate the effects of dipyrone on sensitivity to aspirin (acetylsalicylic acid [ASA]) in patients who underwent peripheral artery vascular reconstruction. Subjects and Methods: Impedance aggregometry and light transmission aggregometry were used to determine the effects of dipyrone on ASA treatment in 21 patients. Blood samples were drawn in a 7-day period after the surgery. The cut-off value for high on-treatment platelet reactivity (HTPR) was set at < 65% of aggregation inhibition for impedance aggregometry. For light transmission aggregometry the cut-off value for arachidonic acid-induced aggregation was set at > 20% of aggregating platelets, and the cut-off value for epinephrine-induced aggregation was > 44% of aggregating platelets. The cut-off value for each method was derived from a large number of patients treated with a daily dose of 100 mg of ASA. Results: We found HTPR in 14 (67%) of the 21 patients. None had primary resistance to ASA, i.e., after the addition of ASA in vitro all samples showed antiplatelet efficacy. Regression analysis showed a possible correlation between lower efficacy of ASA treatment and higher daily doses of dipyrone (p = 0.005 for impedance aggregometry, p = 0.04 for light transmission aggregometry), higher platelet count (p = 0.005 for impedance aggregometry), and shorter time from surgery (p = 0.03 for impedance aggregometry). Conclusion: HTPR occurs in 67% of ASA-treated patients after lower limb vascular surgery. The occurrence of HTPR correlates with the daily dose of dipyrone. Therefore, dipyrone should not be used as a postoperative analgesic in ASA-treated patients after peripheral artery revascularisation due to its influence on the effectiveness of ASA.

scholarly journals Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers

2019 ◽  
Vol 119 (05) ◽  
pp. 735-743 ◽  
Author(s):  
Sukhi Singh ◽  
Tor Damén ◽  
Andreas Nygren ◽  
Caroline Shams Hakimi ◽  
Sofia Ramström ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Clinical Importance ◽  
Receptor Activation ◽  
Clot Formation ◽  
Bleeding Complications ◽  
Impedance Aggregometry ◽  
Perioperative Bleeding ◽  
Adrenaline Infusion ◽  
Induced Aggregation

Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 µg/kg/min. The aggregation increased from median 17 (25−75th percentiles: 14−31) to 25 (21−34) aggregation units (p = 0.012) at 0.10 µg/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22–35] to 46 [38−57%]) and P-selectin expression (from 3.7 [3.0−4.3] to 7.7 [4.7−8.6%]), both p = 0.012. Adrenaline infusion reduced clot formation time (97 [89−110] to 83 [76−90] seconds, p = 0.008) and increased maximum clot firmness (59 [57−60] to 62 [61−64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations. Trial Registry Number ClinicalTrials.gov NCT03441412.

scholarly journals Association of low-voltage areas with the regional wall deformation and the left atrial shape in patients with atrial fibrillation: A proof of concept study

2021 ◽  
Vol 33 ◽  
pp. 100730
Author(s):  
Sotirios Nedios ◽  
Soroosh Sanatkhani ◽  
Michael Oladosu ◽  
Timm Seewöster ◽  
Sergio Richter ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Low Voltage ◽  
Proof Of Concept ◽  
Regional Wall ◽  
Concept Study ◽  
Wall Deformation

Abstract 19503: Durability of Antiplatelet Effect of a Novel Extended-release Formulation of Acetylsalicylic acid, Durlaza in Patients With Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paul A Gurbel ◽  
Kevin Blide P. P Bliden ◽  
Jeff Patrick Patrick ◽  
Katayoon Saadin Saadin ◽  
Udaya Tantry
Keyword(s):  
Adverse Events ◽  
Extended Release ◽  
Platelet Reactivity ◽  
Cvd Risk ◽  
Open Label ◽  
Serious Adverse Events ◽  
Release Formulation ◽  
Antiplatelet Effect ◽  
Immature Platelet Fraction ◽  
Induced Aggregation

Background: High platelet turnover (HPT) is implicated in incomplete platelet inhibition and high platelet reactivity (HPR) during immediate release aspirin therapy in type II diabetes patients (T2DM). Durlaza is a new, extended-release orally administered aspirin formulation developed to provide 24-hour antithrombotic effects with once-daily dosing. Methods: In this open-label, single-center study, T2DM patients (n=40) and a history of cardiovascular disease (CVD) or multiple CVD risk factors were treated with daily 162.5 mg Durlaza for 14±4 days and adverse events were collected. Antiplatelet effects were determined by conventional aggregation (LTA), Multiplate analyzer, thrombelastography with PlateletMapping, PlateletWorks ,VerifyNow Assay, and serum thromboxane B2 (TxB2) at 1, 12, 16, and 24 hrs after the last dose. HPT was defined as immature platelet fraction of ≥3.0% or MPV≥11.0 fl. Patients exhibiting HPT and/or HPR (based on previously published cutpoints in ≥2 assays) were treated with Durlaza at 325mg for 14± 4 days and platelet function testing was repeated. Results: Prevalence of HPT and HPR was 47% and 27%, respectively. There was no loss of antiplatelet effect at 12, 16 and 24 h versus 1 h by all assays (Table 1). All patients responded to 162.5mg Durlaza as measured by arachidonic acid-induced aggregation with LTA and platelet reactivity levels were low at all timepoints (Table). Serum TxB2 was lower at 12 h (p<0.03) as compared to 1 h after 162.5mg and was lower at all times with the 325 mg vs. the 162.5 mg Durlaza (p < 0.05). HPT did not affect the PD profile of Durlaza (Pts with HPT vs. no HPT, p=NS for all). Patients had no serious adverse events and low treatment related AE rate (<5%). Conclusion: In this first comprehensive assessment, a new, extended-release 162.5 Durlaza provided sustained antiplatelet effects over 24 h in T2DM patients with a favorable safety profile. Doubling the dose further lowered serum TxB2 in pts with HPT and/or HPR.

Left atrial appendage occlusion

2018 ◽  
pp. 703-714
Author(s):  
Sandeep Panikker ◽  
Tim Betts ◽  
Milena Leo
Keyword(s):  
Transient Ischaemic Attack ◽  
Left Atrial ◽  
Thrombus Formation ◽  
Blood Stasis ◽  
Progressive Increase ◽  
Thromboembolic Events ◽  
Mortality And Morbidity ◽  
Left Atrial Appendage Occlusion ◽  
Ischaemic Attack ◽  
Prior Stroke

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1.5–2% of the general population and more than 8% of those older than 80 years. Because of the progressive ageing of our population, an exponential increase in incidence is expected over the next few decades. Patients with AF have an increased mortality and morbidity, particularly owing to fatal or disabling stroke. The risk of embolic stroke is five times higher in the presence of AF, with an average annual rate around 5%, but there is a progressive increase with age and the presence of other risk factors, such as prior stroke or transient ischaemic attack, hypertension, diabetes mellitus, congestive heart failure, female sex, and vascular disease, as predicted by the CHADS2 and the CHA2DS2-VASc scores. Moreover, strokes associated with AF are more severe, with a 50% greater likelihood of becoming disabled or handicapped and more than 50% likelihood of death. Intracardiac thrombus formation due to the Virchow triad of events (endothelial or endocardial damage or dysfunction, abnormal blood stasis, and altered haemostasis, platelet function, and fibrinolysis) followed by distal embolization leads to thromboembolic events manifest as transient ischaemic attack, ischaemic stroke, and peripheral embolism in patients with AF.

Locating And Monitoring The Activity Of Intracardiac Thrombi With Indium-111 Platelet Scintigraphy

1981 ◽  
Author(s):  
M D Ezekowitz ◽  
E O Smith ◽  
A C Cox ◽  
S W Herren ◽  
F B Taylor
Keyword(s):  
Artery Bypass ◽  
Inhibitory Response ◽  
Left Ventricular ◽  
Platelet Recovery ◽  
Platelet Scintigraphy ◽  
Indium 111 ◽  
Induced Aggregation ◽  
Intracardiac Thrombi

Indium-III is 2.8 day half-life gamma emitting radionuclide which is suitable for scintigraphic study and has been used to label platelets without causing significant attenuation of function. The purpose of this study was to utilize this technique for localization of left ventricular mural thrombi in patients with regional LV dysfunction. The patient population consisted of 55 patients between the ages of 24 and 77 (53.4 ± 11.3, mean ± 1SD). Twenty-four required coronary artery bypass surgery with aneurysmectomy for intractable angina and/or heart failure. This provided an opportunity to validate the preoperative findings at surgery. Platelets were separated from 43 ml blood in ACD solution by centrifugation and were labelled in ACD:saline (1:7) solution at a pH of 6.5-7.0. A total of 3.8 ± 2.9 × 109 (mean ± 1SD) platelets labelled with 451.9 ± 111.6 μCi with a final labelling efficiency of 72.1±14.1% were injected IV. Platelet recovery at 15 minutes was 51.1 ± 17.7% (mean ± 1SD). EM studies before and after labelling showed no morphological change due to the labelling procedure. Aggregation of platelets in response to ADP and collagen was not altered significantly during the labelling process. Patients on aspirin showed the expected inhibitory effect of aspirin on collagen and ADP induced aggregation. Patients were imaged in multiple views on at least alternate days for a maximum of 8 days. Seventeen had positive studies. In those patients in which surgical confirmation of the scintigraphic studies was possible, a sensitivity of 72% and specificity of 100% was found. We conclude that: 1) Indium-111 platelet scintigraphy promises to be a reliable method of identifying intracardiac thrombi. 2) It may also be useful in monitoring thrombus activity in vivo. 3) Patients on aspirin incorporated platelets onto the thrombus surface in spite of showing the expected inhibitory response to ADP and collagen induced aggregation in vitro.

o-Raffinose cross-linked hemoglobin improves the hemostatic defect associated with anemia and thrombocytopenia in rabbits

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3630-3636 ◽  
Author(s):  
David H. Lee ◽  
Leslie Bardossy ◽  
Nichole Peterson ◽  
Morris A. Blajchman
Keyword(s):  
Blood Loss ◽  
Bleeding Time ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Clinical Settings ◽  
No Donor ◽  
Hemostatic Effect ◽  
Circulating Levels

Abstract Several different preparations of cross-linked hemoglobin (CLHb) are being evaluated for their efficacy and safety as red cell substitutes in a variety of preclinical and clinical settings. Because CLHb is known to sequester nitric oxide (NO) and inhibit NO-mediated processes, we hypothesized that CLHb would have a hemostatic effect by enhancing platelet reactivity, inducing vasoconstriction, or both. Infusion of o-raffinose CLHb shortened the prolonged microvascular bleeding time and decreased blood loss from ear incisions in rabbits rendered anemic and thrombocytopenic. Moreover, this hemostatic effect persisted for at least 24 hours after infusion. Phenylephrine induced a degree of vasoconstriction similar to that induced by CLHb but did not shorten the bleeding time or decrease blood loss, suggesting that vasoconstriction alone cannot account for the hemostatic effect of CLHb. There was no evidence of CLHb-induced activation of coagulation in vivo, since infusion of CLHb did not increase circulating levels of thrombin-antithrombin complex. In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets. This potentiating effect was not attenuated by the addition of superoxide dismutase or catalase. To evaluate the potential arterial thrombogenicity of CLHb, a model of carotid artery thrombosis was developed in rabbits without thrombocytopenia or anemia. Compared with albumin infusion, CLHb infusion shortened the time to complete carotid occlusion. These data suggest that CLHb may shift the thromboregulatory balance toward clot formation, resulting in decreased bleeding in anemic and thrombocytopenic rabbits and possibly increasing arterial thrombogenicity in normal rabbits.

Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover

2016 ◽  
Vol 116 (11) ◽  
pp. 941-948 ◽  
Author(s):  
Thomas Nührenberg ◽  
Michael Amann ◽  
Marco Cederqvist ◽  
Pascal Kleiner ◽  
Christian M. Valina ◽  
...  
Keyword(s):  
Platelet Count ◽  
Drug Exposure ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Underlying Mechanism ◽  
Entire Cohort ◽  
Reticulated Platelets ◽  
Impedance Aggregometry ◽  
The Impact

SummaryReticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all timepoints (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Hypoxia Modulates Platelet Purinergic Signalling Pathways

2019 ◽  
Vol 120 (02) ◽  
pp. 253-261 ◽  
Author(s):  
Gordon G. Paterson ◽  
Jason M. Young ◽  
Joseph A. Willson ◽  
Christopher J. Graham ◽  
Rebecca C. Dru ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Platelet Reactivity ◽  
Clinical Importance ◽  
Adenosine Diphosphate ◽  
Purinergic Signalling ◽  
Systematic Assessment ◽  
Vasp Phosphorylation ◽  
The Impact ◽  
Induced Aggregation

Abstract Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. Methods Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. Results Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. Conclusion Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.

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