scholarly journals Platelet-to-lymphocyte and Neutrophil-to-lymphocyte Ratios Predict Target Vessel Restenosis after Infrainguinal Angioplasty with Stent Implantation

2020 ◽  
Vol 9 (6) ◽  
pp. 1729 ◽  
Author(s):  
Silvia Lee ◽  
Timothy Hoberstorfer ◽  
Patricia P. Wadowski ◽  
Christoph W. Kopp ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Limb Ischemia ◽  
Target Vessel ◽  
Light Transmission Aggregometry ◽  
Platelet Aggregate ◽  
Artery Disease ◽  
Underlying Mechanisms ◽  
Angioplasty And Stenting

Platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte (LMR) ratios are associated with the occurrence of critical limb ischemia in peripheral artery disease (PAD). We therefore investigated whether PLR, NLR or LMR are linked to target vessel restenosis (TVR) following infrainguinal angioplasty and stenting. Moreover, we studied on-treatment platelet reactivity and neutrophil-platelet aggregate (NPA) formation as potential underlying mechanisms. Platelet, neutrophil, lymphocyte and monocyte counts were determined one day after angioplasty and stenting in 95 stable PAD patients. Platelet reactivity and NPA formation in response to protease-activated receptor−1 stimulation were measured by light transmission aggregometry (LTA) and flow cytometry, respectively. PLR and NLR were significantly higher in patients who subsequently developed TVR (both p < 0.05). In contrast, LMR did not differ significantly between patients without and with TVR (p = 0.28). A PLR ≥ 91 and NLR ≥2.75 were identified as the best thresholds to predict TVR, providing sensitivities of 87.5% and 81.3%, and specificities of 34.9% and 50.8%, respectively, and were therefore defined as high PLR and high NLR. TVR occurred significantly more often in patients with high PLR and high NLR than in those with lower ratios (both p < 0.05). Patients with high PLR and high NLR exhibited significantly increased on-treatment platelet aggregation compared to those with lower ratios, and patients with high PLR had higher levels of NPA formation (all p < 0.01). In conclusion, PLR and NLR predict TVR after infrainguinal angioplasty with stent implantation. Platelet activation and neutrophil-platelet interaction may be involved in the underlying pathomechanisms

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Pharmacology ◽  
2018 ◽  
Vol 103 (1-2) ◽  
pp. 23-29 ◽  
Author(s):  
Amin Polzin ◽  
Lisa Dannenberg ◽  
Theresa Schneider ◽  
Betül Knoop ◽  
David Naguib ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Operating Characteristic ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Area Under The Curve ◽  
Healthy Individuals ◽  
Antibody Assay ◽  
Light Transmission Aggregometry ◽  
Artery Disease

Aspirin is essential in secondary prevention of patients after myocardial infarction and with coronary artery disease. However, impaired pharmacodynamic response to aspirin is frequent (high on-treatment platelet reactivity [HTPR]). This leads to an enhanced prevalence of cardiovascular events and to an impaired clinical outcome. The current specific assays to evaluate aspirin antiplatelet effects are complex, time-consuming and demand for a high laboratory expertise. Therefore, we developed a potentially bedside assay based on the determination of malondialdehyde (MDA). MDA is a by-product of the thromboxane (TX) formation, which is synthesized in equimolar concentrations. In this study, we compared this MDA assay to the conventional assays in determination of pharmacodynamic aspirin response. For this, aspirin antiplatelet effects were measured in 22 healthy individuals and 63 aspirin treated patients using TX B2 formation enzyme-linked antibody assay, arachidonic acid induced light transmission aggregometry (LTA) and the new fluorometric MDA assay. In patients, MDA levels correlated well with TX formation (R = 0.81; 95% CI 0.69–0.88; p < 0.001) and LTA (R = 0.84; CI 0.74–0.91; p < 0.001). Receiver operating characteristic analyses revealed that the MDA assay does detect HTPR to aspirin sufficiently (area under the curve: 0.965; p < 0.001). The optimal cut-off was > 128 nmol/L (sensitivity of 100%, specificity of 91%). The new MDA assay is reliable in detecting HTPR. It is highly specific in the evaluation of antiplatelet effects by aspirin. This promising and potential bedside assay needs to be evaluated in clinical practice.

Comparison of VASP-phosphorylation assay to light-transmission aggregometry in assessing inhibition of the platelet ADP P2Y12 receptor

2006 ◽  
Vol 96 (12) ◽  
pp. 767-773 ◽  
Author(s):  
Agnieszka Pampuch ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Light Transmission ◽  
Platelet Reactivity ◽  
Flow Cytometric Analysis ◽  
Individual Variability ◽  
P2y12 Receptor ◽  
Reactivity Index ◽  
Drug Induced ◽  
Light Transmission Aggregometry ◽  
Adp Receptor

SummaryThere is need to improve platelet function testing to monitor the response to antiplatelet drugs. We compared flow-cytometric analysis of intraplatelet vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) to light-transmission aggregometry for the detection of drug-induced in-vitro inhibition of the platelet P2Y12 ADP receptor on 22 healthy subjects (10 males, 12 females, 28.5 ± 6.6 years). The platelet reactivity index (PRI) of VASP was calculated both from mean fluorescence intensity (MFI) and percent of fluorescence-positive platelets in the presence of PGE1 with or without ADP (10 µM). Platelet aggregation was induced by ADP (1.25, 2.5 and 5 µM). Cangrelor, a competitive inhibitor of the P2Y12 receptor, preincubated 5 minutes, induced a concentration-dependent inhibition of platelet ADP-receptor function in both tests. Indeed PRI (%) based on either MFI or percent platelets gated were highly correlated with each other (r = 0.97, p<0.0001) and with aggregation in- duced by ADP. The IC50 of cangrelor against each of the three ADP concentrations used in aggregometry increased from 5.8 ± 3.4 nM to 23.1 ± 4.0 nM and to 98 ± 25 nM, respectively. The IC50 of cangrelor based on VASP-P was within the same range (25.5 ± 7.7 nM). No correlation was observed between IC50 values of cangrelor and ADP concentrations giving 50% effect (EC50) in the absence of the drug. However, at 10 nM cangrelor seven subjects could be identified by the VASP-P assay as “low responders” to the drug (PRI> 50%), and six of them also had an aggregation response to 5 µM ADP > 50%. These six subjects showed the lowest ADP EC50 values in the absence of the drug, possibly reflecting high sensitivity of their platelet P2Y12 receptors to ADP. In conclusion, both the VASP-P assay and light-transmission aggregometry detect in a comparable way in-vitro pharmacological inhibition of the platelet P2Y12 ADP receptor and its individual variability.

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.

Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation

2009 ◽  
Vol 101 (02) ◽  
pp. 333-339 ◽  
Author(s):  
Sabine Steiner ◽  
Daniela Seidinger ◽  
Renate Koppensteiner ◽  
Thomas Gremmel ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Percutaneous Intervention ◽  
Adverse Outcomes ◽  
Gold Standard Method ◽  
Platelet Aggregometry ◽  
Increased Risk ◽  
The Impact

SummaryA high on-treatment residual ADP-inducible platelet reactivity in light transmission aggregometry (LTA) has been associated with an increased risk of adverse outcomes after percutaneous coronary intervention (PCI). However, LTA is weakly standardized, and results obtained in one laboratory may not be comparable to those obtained in another one. We therefore sought to determine the test correlating best with LTA to estimate clopidogrel-mediated platelet inhibition in 80 patients on dual antiplatelet therapy after elective percutaneous intervention with stent implantation. We selected the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode platelet aggregometry and the Impact-R for comparisons with LTA. Cut-off values for residual ADP-inducible platelet reactivity were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on the results from LTA. The results from all four assays correlated significantly with those from LTA. The VerifyNow P2Y12 assay revealed the strongest correlation (r = 0.61, p < 0.001). Sensitivities and specificities ranged from 35% to 55%, and from 78.3% to 85%, respectively. In conclusion, although all assays correlated significantly with LTA, they need to be improved to become clinically used diagnostic tests. Further, it may be too early to define the gold standard method for assessing residual ADP-inducible platelet reactivity and generally acceptable cut-off values.

miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression

2019 ◽  
Vol 119 (09) ◽  
pp. 1451-1460
Author(s):  
Wen Wen Liu ◽  
Hao Wang ◽  
Xia Huan Chen ◽  
Sidney W. Fu ◽  
Mei Lin Liu
Keyword(s):  
Platelet Aggregation ◽  
Bioinformatics Analysis ◽  
Light Transmission ◽  
Lower Quartile ◽  
Thromboxane Synthase ◽  
Gene Profiles ◽  
Light Transmission Aggregometry ◽  
Cell Proliferation Inhibition ◽  
Human Blood Samples ◽  
Artery Disease

AbstractAspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes—PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B—and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B2 (TXB2) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3′-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.

A 70-Year-Old Female with Unexpected Platelet Function Testing Results

2019 ◽  
Vol 51 (3) ◽  
pp. 310-314
Author(s):  
Moon Joo Kim ◽  
Pragna Patel ◽  
Niti Vyas ◽  
Christopher Leveque ◽  
Orlando Diaz ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
P2y12 Inhibitor ◽  
Light Transmission Aggregometry ◽  
P2y12 Reaction Unit ◽  
History Of ◽  
Reaction Unit ◽  
The Mean ◽  
Function Testing

Abstract A 70-year-old female with a history of hypertension and left A2 segment aneurysm was scheduled for pipeline embolization device (PED) placement. Preinterventional antiplatelet prophylaxis included aspirin and ticagrelor. Unexpectedly, after 13 days of treatment, VerifyNow showed a P2Y12 reaction unit (PRU) value of 216, approximately &gt;5 times the mean PRU of other patients on aspirin and ticagrelor. We confirmed platelet reactivity and ticagrelor resistance with light transmission aggregometry. Antiplatelet therapy was switched to prasugrel, and aspirin was continued. Eight days later, the P2Y12 reaction value (PRU) was 164. PED was placed without complications. Unlike clopidogrel, ticagrelor is a direct P2Y12 inhibitor that does not require metabolism to an active metabolite. Ticagrelor resistance is very rarely reported. To the best of our knowledge, there has been no case of ticagrelor resistance reported in the context of pre-PED placement prophylaxis.

scholarly journals Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status

2017 ◽  
Vol 117 (05) ◽  
pp. 940-947 ◽  
Author(s):  
Mark R. Thomas ◽  
Dominick J. Angiolillo ◽  
Marc P. Bonaca ◽  
Ramzi A. Ajjan ◽  
Heather M. Judge ◽  
...  
Keyword(s):  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Inhibitory Effect ◽  
Post Dose ◽  
Pharmacodynamic Response ◽  
Diabetes Status ◽  
Light Transmission Aggregometry ◽  
Patients With Diabetes ◽  
High Level

SummaryDiabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 ?M: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.

Evaluation of Residual Platelet Reactivity in Patients Treated with Aspirin and or Clopidogrel: Comparison of Results Obtained On Multiplate®, PFA-100TM and Classical Light Transmission Aggregometry.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3129-3129
Author(s):  
Annick Ankri ◽  
Isabelle Martin-Toutain ◽  
Anne Baranger ◽  
Marie-Claude Couty ◽  
Jean Philippe Collet ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Biological Activities ◽  
Impedance Aggregometry ◽  
Increased Risk ◽  
Light Transmission Aggregometry ◽  
Group A ◽  
Platelet Functions ◽  
Good Agreement

Abstract Abstract 3129 Poster Board III-66 Residual platelet reactivity (RPR), despite antiplatelet therapy (AT), is currently associated with an increased risk of recurrent ischemic events and is linked to a biological resistance to AT. We determined whether whole blood impedance aggregometry using the Multiplate® (Dynabyte and IL France) detects the effects of AT as reliably as does classical light transmission aggregometry (LTA) (PAP-8, Biodis). We compared also results with those obtained on PFA-100TM (Siemens). Patients and Methods Ninety-three controls, healthy volunteers or patients without intake of AT or other drugs or pathology impairing platelet functions and 182 consecutive patients on AT were studied. Among patients, 61 received Aspirin 100mg (group A), 36 Clopidogrel 75mg (group C) and 85 the association of the two drugs. Among these 85 patients, 58 received continuously Aspirin 75mg and Clopidogrel 75mg (group AC) and 27 received a loading dose for both drugs before coronarography (group LAC). Venous blood samples were obtained on Becton Dickinson vacutainer containing citrate 0.129M. Multiplate® measures change in electrical resistance as arbitrary aggregation units (AU) over time. Aggregation is quantified as AU and area under the curve (AUC) of AU.min. On LTA, aggregation was quantified according to manufacturer's recommendations as AUC. “Resistance” to Aspirin or Aspirin RPR was determined on Multiplate® (M) using arachidonic acid at 0.5 mM (ASPITEST), in LTA with arachidonic acid at 1 mM (AA-LTA) and on PFA-100TM using the cartridge with membrane coated with epinephrine (PFA-EPI). In the same way, “resistance” to Clopidogrel was determined on M using ADP at 6.4 μM (ADPTEST), in LTA with the presence of ADP at 10 μM (ADP-LTA) and occlusion time on PFA-100TM using cartridge with membrane coated with ADP (PFA-ADP). Results All patients were tested on M, 169 on PFA-100TM and 37 with LTA. Significant correlations (p<.0001) were observed between ASPITEST and AA-LTA (r = .771), ASPITEST and PFA-EPI (r = -.42), AA-LTA and PFA-EPI (r = -.47), ADPTEST and ADP-LTA (r = .6) ADPTEST and PFA-ADP (r = -.39) and ADP-LTA and PFA-ADP (r = -.56). To define RPR on M and LTA, cut-off values (5th percentile) were determined from controls for each inducer. Treated patients presenting reactivity higher than the threshold value were considered as ‘resistant’. For PFA-100TM, results of patients under cut-off point defined by the manufacturer were considered as ‘resistant’. The frequency of “resistant” patients according to the different platelet functions tests was: a) for Aspirin: 10% on M, 4.5% with LTA and 32.8% with PFA-EPI. b) for Clopidogrel 23.1% on M 16.1% with LTA and 54.5% with PFA-ADP. A good agreement was found between ASPITEST and AA-LTA and between ADPTEST and ADP-LTA (respectively 92% and 88.7%). On the other hand, results on comparison between ASPITEST and PFA-EPI and LTA and PFA-EPI were respectively 70% and 72.6%. Results for ADPTEST and PFA-ADP were 69% and 72.3% for ADP-LTA and PFA-ADP. A significant gradation of mean AUC was observed using ASPITEST on M between all groups of subjects: controls (mean = 494±176); group A (mean = 214±186); group C (mean = 310±198); group AC (mean = 118±109); group LAC (mean = 74±45). Similar results are obtained with LTA and on PFA-100TM (except for the group C, Clopidogrel alone). Thus, a potentiating effect of Aspirin by the association with Clopidogrel may be postulated in this study. Using ADPTEST to assess the treatment response by clopidogrel, mean AUC were significantly lower for all group of patients with Clopidogrel than for controls. No gradient has been observed. Mean AUC of patients with Aspirin alone was similar to controls. In conclusion, our results confirm that Multiplate® is more effective than PFA-100TM in monitoring patients on AT. The good agreement between Multiplate® and LTA could lead to use the Multiplate® in first intention to detect RPR in these patients. Furthermore the easiness of Multiplate® use may contribute to development of new studies on biological activities of AT. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document