Decreased platelet inhibition by P2Y12 receptor blockers in anaemia

Wadowski, Patricia P.; Kopp, Christoph W.; Koppensteiner, Renate; Lang, Irene M.; Pultar, Joseph; Lee, Silvia; Weikert, Constantin; Panzer, Simon; Gremmel, Thomas

doi:10.1111/eci.12861

Cited by 17 publications

(12 citation statements)

References 34 publications

(52 reference statements)

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“…6,40 Hemoglobin was independently associated with platelet aggregation as measured by the VerifyNow P2Y 12 assay and the Impact-R, which is also in line with prior results. 41 Triglyceride levels remained independently associated with both platelet activation and aggregation by the applied test methods after multivariate regression analyses. This is in line with previous reports of increased platelet reactivity in hypertriglyceridemia.…”

Section: Discussionmentioning

confidence: 88%

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

et al. 2018

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Low high-density lipoprotein cholesterol (HDL-C) levels are an independent predictor of ischemic events in patients with atherosclerotic cardiovascular disease. This may in part be due to decreased clopidogrel-mediated platelet inhibition in patients with low HDL-C. We investigated the association of HDL-C with on-treatment platelet reactivity to adenosine diphosphate (ADP) in 314 patients on dual antiplatelet therapy with clopidogrel and aspirin undergoing angioplasty and stenting. Platelet P-selectin expression was assessed by flow cytometry, and platelet aggregation was determined by the VerifyNow P2Y assay and the Impact-R. High-density lipoprotein cholesterol levels were inversely associated with P-selectin expression and the VerifyNow P2Y assay (both P ≤ .01). Moreover, we found a positive correlation of HDL-C with surface coverage by the Impact-R ( P = .003). Patients with low HDL-C (≤35 mg/dL) exhibited a significantly higher P-selectin expression in response to ADP and higher platelet aggregation by the VerifyNow P2Y assay and the Impact-R than patients with normal HDL-C (>35 mg/dL; all P < .05). High on-treatment residual platelet reactivity by the VerifyNow P2Y assay occurred significantly more frequently in patients with low HDL-C levels than in those with normal HDL-C (47.4% vs 30.1%, P = .01). In conclusion, low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting.

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Section: Discussionmentioning

confidence: 88%

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

et al. 2018

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“…In another study, we could demonstrate decreased platelet inhibition by P2Y12 receptor antagonists in anemic patients after elective and acute angioplasty for CAD. 10 Moreover, anemia has previously been associated with an increased risk for ischemic events over the course of 2 years in patients undergoing PCI. 11 Although not reaching statistical significance, patients with low MCV had a higher rate of anemia and lower hemoglobin level and hematocrit.…”

Section: Discussionmentioning

confidence: 99%

“…9 Anemia is associated with increased platelet reactivity, decreased platelet inhibition by antiplatelet therapy, and adverse outcomes in patients with cardiovascular disease. 10,11 Also, structural elements of RBC have been linked to morbidity and mortality in various conditions. [12][13][14] Mean corpuscular volume (MCV) has recently emerged as a potential predictor of adverse events in coronary artery disease (CAD).…”

Section: Introductionmentioning

confidence: 99%

Mean Corpuscular Volume Predicts Adverse Outcomes Following Peripheral Angioplasty With Stenting and Is Associated With On-Treatment Platelet Reactivity

et al. 2020

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Structural aspects of red blood cells have been associated with cardiovascular disease. No data linking mean corpuscular volume (MCV) to clinical outcomes and on-treatment platelet reactivity in patients with peripheral artery disease (PAD) are available. We investigated a composite of atherothrombotic events and target vessel restenosis or reocclusion following infrainguinal stenting for stable PAD. Residual platelet reactivity was measured by light transmission aggregometry (LTA) and the VerifyNow assays. We included 104 patients receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. In receiver-operating characteristic analysis, MCV effectively discriminated between patients with and without adverse outcomes and identified a MCV ≤90.8 fL as optimal cutoff. Adverse outcomes occurred significantly more often in patients with low MCV (log-rank P = .002). In univariable Cox regression analysis, low MCV was associated with an increased risk of future adverse outcomes (hazard ratio [HR]: 2.662 [95%CI: 1.304-5.434]; P = .007) and remained significantly associated after adjustment (HR: 2.591 [95%CI: 1.242-5.403]; P = .011). Mean corpuscular volume was inversely correlated with arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by LTA and with the VerifyNow aspirin assay. Low MCV is associated with adverse outcomes over 2 years following infrainguinal stenting. Mean corpuscular volume correlates inversely with AA- and ADP-inducible platelet reactivity during DAPT.

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“…This is most likely due to the fact that clopidogrel is a prodrug requiring 2 steps of hepatic biotransformation to become pharmacologically active, while prasugrel needs only 1 step of hepatic metabolization and ticagrelor acts directly without prior modification . Its complex metabolism predisposes clopidogrel‐mediated platelet inhibition to alteration by various factors like genetic polymorphisms, co‐medication, age, sex, hemoglobin levels, renal function, smoking, and obesity . In contrast to clopidogrel, prasugrel and ticagrelor provide a stronger and more consistent antiplatelet effect.…”

Section: Discussionmentioning

confidence: 99%

Protease‐activated receptor‐mediated platelet aggregation in acute coronary syndrome patients on potent P2Y12 inhibitors

Wadowski

Pultar

Weikert

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Background Despite the increasing use of potent P2Y12 inhibitors, further atherothrombotic events still impair the prognosis of many acute coronary syndrome (ACS) patients. This may in part be attributable to intact platelet aggregation via the human thrombin receptors protease‐activated receptor (PAR)‐1 and PAR‐4. Objective We studied PAR mediated platelet aggregation in ACS patients following percutaneous coronary intervention (PCI) with stent implantation in a cross‐sectional study. Methods Platelet aggregation to ADP as well as to the PAR‐1 agonist SFLLRN and the PAR‐4 agonist AYPGKF was assessed by multiple electrode aggregometry in 194 ACS patients on dual antiplatelet therapy with aspirin and either prasugrel (n = 114) or ticagrelor (n = 80) 3 days after PCI. Results Based on the consensus cutoff value, high on‐treatment residual platelet reactivity to ADP (HRPR ADP) was observed in only 2 prasugrel‐treated patients. Both patients with HRPR ADP had also a normal response to SFLLRN and AYPGKF. Among the 112 prasugrel‐treated patients with adequate P2Y12 inhibition, 50 patients (45%) still had a normal response to SFLLRN, and 70 patients (63%) still had a normal response to AYPGKF. Among the 80 ticagrelor‐treated patients with adequate P2Y12 inhibition, 25 patients (31%) still had a normal response to SFLLRN, and 50 (63%) still had a normal response to AYPGKF. Conclusion Normal platelet aggregation via PAR‐1 and PAR‐4 is preserved in many patients with adequate P2Y12 inhibition by prasugrel and ticagrelor. The present findings may at least in part explain adverse ischemic events despite potent P2Y12 inhibition.

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Decreased platelet inhibition by P2Y12 receptor blockers in anaemia

Abstract: Background: Anaemic patients undergoing angioplasty and stenting are at an

Cited by 17 publications

References 34 publications

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

Mean Corpuscular Volume Predicts Adverse Outcomes Following Peripheral Angioplasty With Stenting and Is Associated With On-Treatment Platelet Reactivity

Protease‐activated receptor‐mediated platelet aggregation in acute coronary syndrome patients on potent P2Y12 inhibitors

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