Effect of Blood Hematocrit and Erythrocyte Deformability on Adenosine 5′-Diphosphate Platelet Reactivity in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy

Abstract

Previous studies have explored the association between hemorheologic alterations and aspirin resistance, pointing out the possible interaction between hematologic components and platelet responsiveness to antiplatelet drugs. The aim of this study was to evaluate the association between hemorheologic variables and residual platelet reactivity in patients with acute coronary syndromes (ACSs) who underwent percutaneous coronary intervention on dual antiplatelet therapy. The study population included 528 patients with ACSs. Hemorheologic studies were performed by assessing whole blood viscosity at 0.512 and 94.5/ second, plasma viscosity, and erythrocyte deformability index. Post-treatment platelet reactivity was investigated by measuring platelet aggregation by adenosine 5=-diphosphate (ADP) 10 mol and a value >70% was defined as high ADP platelet reactivity. Significantly (p <0.01) lower values of hematocrit and erythrocyte deformability and higher values of whole blood viscosity at 94.5/second were found in patients with high ADP platelet reactivity. At multivariate analysis, lower values of hematocrit and erythrocyte deformability index and higher values of whole blood viscosity at 94.5/second and leukocytes (highest vs lowest tertile) also resulted in an independent association with high platelet reactivity, except for leukocytes, after simultaneous adjustment for hematocrit, leukocyte count, and erythrocyte deformability index. In conclusion, these results demonstrate the influence of hematocrit and of erythrocyte deformability on ADP platelet reactivity. These variables could be considered to optimize treatment with antiplatelet therapy in these patients. Use of clopidogrel in addition to acetylsalicylic acid has been demonstrated to be associated with a decrease of cardiovascular events in patients with acute coronary syndromes (ACSs) independently of stent implantation.1,2 Retrospective studies have shown that discontinuation of clopidogrel, even Ն6 months after stent implantation, is associated with an increased risk of thrombotic events in patients with drug-eluting stents.3,4 However, interindividual variabilities in response to clopidogrel and acetylsalicylic acid have been reported in patients with ACS.5 From these assumptions, the phenomenon of clopidogrel resistance has progressively gained great interest 6,7 and recent studies have shown that decreased responsiveness to clopidogrel is associated with an increased incidence of death and cardiovascular events 8 and is a strong predictor of stent thrombosis after drug-eluting stent implantation.9 Previous studies have reported an association between hemorheologic variables and aspirin resistance.10,11 The aim of this study was to evaluate the possible association between hemorheologic variables and residual platelet reactivity to adenosine 5=-diphosphate (ADP) in patients with ACS on dual antiplatelet therapy. MethodsThe study population included 528 consecutive patients with a diagnosis of ACS, 272 with ST-segment elevation myocardial infarction (STEM...

Clinical importance of aspirin and clopidogrel resistance

“…Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (OR 5.92, 95% CI: 1.83-16.9, P < 0.001). The importance of impaired hemorheological parameters in the development of aspirin resistance was confirmed by another study conducted by our workgroup and it was also confirmed by independent studies [50,51] . One potential explanation is when plasma fibrinogen levels increase red blood cells adhere and release ADP, which is a potential agonist of platelet aggregation.…”

N-3 polyunsaturated fatty acids do not influence the efficacy of dual antiplatelet therapy in stable angina pectoris patients after percutaneous coronary intervention

“…These findings are in accordance with previously published observations [23,24] and suggest that the analysis of standard morphology, i.e. PTL count, may be helpful in the prediction of ASA and CLO responsiveness.…”

Determinants to optimize response to clopidogrel in acute coronary syndrome

“…Some hemorheologic variables are also associated with high on-treatment platelet reactivity in patients with ACS on dual antiplatelet therapy. In particular, decreased erythrocyte deformability is significantly associated with increased platelet aggregation induced by ADP 29. A possible explanation for this association is that erythrocytes with decreased deformability tend to release a larger amount of ADP in the circulation compared to those without93 and this released ADP can compete with clopidogrel for purinergic receptors present on the platelet surface.…”