Red cell distribution width, other hematological parameters and atherogenic index of plasma in patients with clopidogrel and aspirin resistance

Year 2016, Volume: 2 Issue: 3, 200 - 205, 04.11.2016

Yasemin Ustundag Budak Kagan Huysal Sanem Karadag Gecgel Hasan Ari Mehmet Melek Senol Yavuz Sencer Camci Alper Karakus İbrahim Aktas Selma Ari

https://doi.org/10.18621/eurj.2016.5000200132

Abstract

Objective. Chronic inflammation might favour platelet hyperactivity, which leads to inter-individual variability in antiplatelet resistance. The aim of this study was to test the hypothesis that there is a relationship between some hematological parameters reported as measures of systemic inflammation, the atherogenic index of plasma (AIP), and antiplatelet responsiveness. Methods. This retrospective study included patients receiving aspirin (100 mg) and clopidogrel (75 mg) daily before and after stenting. Platelet inhibition was assessed using the VerifyNow P2Y12 point-of-care test. Resistance to antiplatelet therapy was defined as P2Y12 reactivity exceeding 240 units (for clopidogrel) or aspirin reaction units exceeding 550 units (for aspirin). The AIP was calculated as the logarithm of triglyceride/high density lipoprotein cholesterol. The white blood cell (WBC), platelet (P), neutrophil (N), and lymphocyte (L) counts, red cell distribution width (RDW), hemoglobin (Hb), plateletcrit, mean platelet volume (MPV), platelet distribution width, and N/L and P/L ratios were evaluated. Results. Of 232 patients (73% male; median age, 63 years; range, 38-87 years), 52 (22%) were aspirin resistant and 82 (35%) were clopidogrel resistant; 7.7% were both aspirin and clopidogrel resistant. Median RDW levels were significantly higher (14.4% [interquartile range (IQR) 3] vs. 13.9% [IQR 1.3]; p=0.01) and Hb levels significantly lower (12.0±1.6 g/dL vs. 13.2±1.7 g/dL; p<0.001) in the clopidogrel-resistant patients than in the clopidogrel responders. WBC, AIP, MPV, N/L, and P/L ratios were not statistically significant (p>0.05). Multivariate logistic regression showed that Hb (odds ratio [OR]=0.73; 95% confidence interval [CI], 0.60-0.88; p=0.001) and RDW (OR=1.26; 95% CI, 1.02-1.55; p=0.02) were independent predictors of clopidogrel resistance. Conclusion. Both RDW and Hb were independent variables associated with clopidogrel resistance, but antiplatelet resistance cannot be predicted based on other hematological parameters or AIP. 

Keywords

Red cell distribution width, hematological parameters, atherogenic index of plasma, systemic inflamation, clopidogrel resistance

References

• Wassef AW, Khafaji H, Syed I, Yan AT, Udell JA, Goodman SG, et al. Short duration vs standard duration of dual-antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents- A systematic review, meta-analysis, and meta-regression analysis of randomized controlled trials. J Invasive Cardiol 2016. pii: JIC2016915-2.
• Shirasaka Y, Chaudhry AS, McDonald M, Prasad B, Wong T, Calamia JC, et al. Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content. Pharmacogenomics J 2015;16:375-87.
• Manolis AS, Manolis TA, Papadimitriou P, Koulouris S, Melita H. Combined antiplatelet therapy: still a sweeping combination in cardiology. Cardiovasc Hematol Agents Med Chem 2013;11:136-67.
• Osmancik P, Paulu P, Tousek P, Kocka V, Vidimsky P. High leukocyte count and interleukin-10 predict high on-treatment-platelet-reactivity in patients treated with clopidogrel. J Thromb Thrombolysis 2012;33:349-54.
• Larsen SB, Grove EL, Kristensen SD, Hvas AM. Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary artery disease. Thromb Haemost 2013;109:920-9.
• Caruso R, Rocchiccioli S, Gori AM, Cecchettini A, Giusti B, Parodi G, et al. Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome. Mediators Inflamm 2015;2015:710123.
• Ozer S, Yilmaz R, Sonmezgoz E, Karaaslan E, Taskin S, Butun I, et al. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit 2015;21:298-303.
• Dobiasova M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apo B-lipoprotein-depleted plasma. Clin Biochem 2001;34:583-8.
• Karepov V, Tolpina G, Kuliczkowski W, Serebruany V. Plasma triglycerides as predictors of platelet responsiveness to aspirin in patients after first ischemic stroke. Cerebrovasc Dis 2008;26:272-6.
• Song TJ, Suh SH, Min PK, Kim DJ, Kim BM, Heo JH, et al. The influence of anti-platelet resistance on the development of cerebral ischemic lesion after carotid artery stenting. Yonsei Med J 2013;54:288-94.
• Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: A simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci 2015;52:86-105.
• Fornal M, Wizner B, Cwynar M, Krolczyk J, Kwater A, Korbut RA, et al. Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension. Clin Hemorheol Microcirc 2014;56:325-35.
• Vaya A, Sarnago A, Fuster O, Alis R, Romagnoli M. Influence of inflammatory and lipidic parameters on red blood cell distribution width in a healthy population. Clin Hemorheol Microcirc 2015;59:379-85.
• Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol 2014;5:84.
• Tresukosol D, Suktitipat B, Hunnangkul S, Kamkaew R, Poldee S, Tassaneetrithep B, et al. Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease. PLoS One 2014;9:e110188.
• Volpi E, Giusti L, Ciregia F, Da Valle Y, Giannaccini G, Berti S, et al. Platelet proteome and clopidogrel response in patients with stable angina undergoing percutaneous coronary intervention. Clin Biochem 2012;45:758-65.
• Tziakas D, Chalikias G, Grapsa A, Gioka T, Tentes I, Konstantinides S. Red blood cell distribution width: a strong prognostic marker in cardiovascular disease: is associated with cholesterol content of erythrocyte membrane. Clin Hemorheol Microcirc 2012;51:243-54.
• de Freitas MV, de Oliveira MR, dos Santos DF, et al. Influence of the use of statin on the stability of erythrocyte membranes in multiple sclerosis. J Membr Biol 2010;233:127-34.
• Koter M, Franiak I, Strychalska K, Broncel M, Chojnowska-Jezierska J. Damage to the structure of erythrocyte plasma membranes in patients with type-2 hypercholesterolemia. Int J Biochem Cell Biol 2004;36:205-15.
• Lippi G, Sanchis-Gomar F, Danese E, Montagnana M. Association of red blood cell distribution width with plasma lipids in a general population of unselected outpatients. Kardiol Pol 2013;71:931-6.
• Nada AM. Red cell distribution width in type 2 diabetic patients. Diabetes Metab Syndr Obes 2015;30:525-33.
• Bhatt DL. Aspirin resistance: more than just a laboratory curiosity. J Am Coll Cardiol 2004;43:1127-9.
• Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006;27:647-54.
• Sharma RK, Reddy HK, Singh VN, Sharma R, Voelker DJ, Bhatt G. Aspirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting. Vasc Health Risk Manag 2009;5:965-72.