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Gender-based differences in platelet function and platelet reactivity to P2Y12 inhibitors


Autoři: Marco Ranucci aff001;  Tommaso Aloisio aff001;  Umberto Di Dedda aff001;  Lorenzo Menicanti aff002;  Carlo de Vincentiis aff002;  Ekaterina Baryshnikova aff001
Působiště autorů: Department of Cardiothoracic, Vascular Anaesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy aff001;  Department of Cardiac Surgery, IRCCS Policlinico San Donato, Milan Italy aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225771

Souhrn

Background

Gender influences platelet biology. Women have a larger platelet count, but gender-based differences in platelet function remain debated. We performed a study addressing gender-based differences in platelet function using point-of-care platelet function tests (PFT).

Methods

The patient population consisted of 760 cardiac surgery patients where preoperative PFT (multiple-electrode aggregometry [MEA]) were available. Platelet count and function at the ADPtest and TRAPtest were compared in the overall population and separately in patients with or without residual effects of P2Y12 inhibitors.

Results

Women had a significantly (P = 0.001) higher platelet count but a non-significantly higher platelet reactivity to ADP. In clopidogrel-treated patients, the platelets ADP reactivity was significantly (P = 0.031) higher in women, and platelet count was the main determinant of platelet hyper-reactivity. Within patients under full clopidogrel effects, women with a platelet count ≥ 200,000 cells/μL had a significantly (P = 0.023) higher rate of high-on-treatment platelet reactivity (HTPR, 45.5%) with respect to males with a platelet count < 200,000 cells/μL (11.9%), with a relative risk of 6.2 (95% confidence interval 1.4–29).

Conclusions

Our findings confirm that women have a larger platelet count than men, and that this is associated to a trend towards a higher platelet reactivity. HTPR is largely represented in women with a high platelet count. This generates the hypothesis that women requiring P2Y12 inhibitors could potentially benefit from larger doses of drug or should be treated with anti-platelet agents with a low rate of HTPR.

Klíčová slova:

Body Mass Index – bilirubin – Obesity – Creatinine – Platelets – Platelet aggregation – Cardiac surgery – Hematocrit


Zdroje

1. Patti G, De Caterina R, Abbate R, Andreotti F, Biasucci LM, Calabrò P, et al. Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A 'state-of-the-art' paper. Eur Heart J. 2014;35:2213–2223b. doi: 10.1093/eurheartj/ehu279 25024407

2. Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature. 1975;253:355–357. doi: 10.1038/253355a0 1110780

3. Stevens RF, Alexander MK. A sex difference in the platelet count. Br J Haematol. 1977; 37:295–300. doi: 10.1111/j.1365-2141.1977.tb06847.x 603762

4. Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol. 2006;16:12

5. Faraday N, Goldschmidt-Clermont PJ, Bray PF. Gender differences in platelet GPIIb-IIIa activation. Thromb Haemost. 1997;77:748–754. 9134654

6. Haque SF, Matsubayashi H, Izumi S, Sugi T, Arai T, Kondo A, et al. Sex difference in platelet aggregation detected by new aggregometry using light scattering. Endocr J. 2001;48:33–41. doi: 10.1507/endocrj.48.33 11403101

7. Zwierzina WD, Kunz F, Kogelnig R, Herold M. Sex-related differences in platelet aggregation in native whole blood. Thromb Res. 1987;48:161–171. doi: 10.1016/0049-3848(87)90412-9 3122357

8. Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996; 334:1090–1094. doi: 10.1056/NEJM199604253341703 8598867

9. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373:1849–1860. doi: 10.1016/S0140-6736(09)60503-1 19482214

10. Wang TY, Angiolillo DJ, Cushman M, Sabatine MS, Bray PF, Smyth SS, et al. Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease. J Am Coll Cardiol. 2012;59:891–900. doi: 10.1016/j.jacc.2011.09.075 22381424

11. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015. doi: 10.1056/NEJMoa0706482 17982182

12. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–1057. doi: 10.1056/NEJMoa0904327 19717846

13. Berger JS, Bhatt DL, Cannon CP, Chen Z, Jiang L, Jones JB, et al. The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis. J Am Coll Cardiol. 2009; 54:1935–1945. doi: 10.1016/j.jacc.2009.05.074 19909874

14. Dehghani P, Lavoie A, Lavi S, Crawford JJ, Harenberg S, Zimmermann RH, et al. Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI. Am Heart J. 2017;192:105–112. doi: 10.1016/j.ahj.2017.07.013 28938956

15. Ottani F, Femia EA, Cattaneo M, Caravita L, Attanasio C, Galvani M. Switching from clopidogrel to prasugrel to protect early invasive treatment in acute coronary syndromes: Results of the switch over trial. Int J Cardiol. 2018;255:8–14. doi: 10.1016/j.ijcard.2017.12.055 29336914

16. Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, et al. Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation. 2016;134:780–792. doi: 10.1161/CIRCULATIONAHA.116.023402 27559041

17. Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013;6:1111–1128. doi: 10.1016/j.jcin.2013.06.011 24262612

18. Di Dedda U, Ranucci M, Baryshnikova E, Castelvecchio S; Surgical and Clinical Outcome Research Group. Thienopyridines resistance and recovery of platelet function after discontinuation of thienopyridines in cardiac surgery patients. Eur J Cardiothorac Surg. 2014;45:165–170. doi: 10.1093/ejcts/ezt279 23828846

19. Ranucci M, Colella D, Baryshnikova E, Di Dedda U; Surgical and Clinical Outcome Research (SCORE) Group. Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery. Br J Anaesth. 2014;113:970–976. doi: 10.1093/bja/aeu315 25209096

20. Ranucci M, Pistuddi V, Di Dedda U, Menicanti L, De Vincentiis C, Baryshnikova E; Surgical and Clinical Outcome REsearch (SCORE) group. Platelet function after cardiac surgery and its association with severe postoperative bleeding: the PLATFORM study. Platelets. 2018; doi: 10.1080/09537104.2018.1535706 30365338

21. Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013; 62:2261–2273. doi: 10.1016/j.jacc.2013.07.101 24076493

22. Ranucci M, Baryshnikova E, for The Surgical And Clinical Outcome Research Score Group. The interaction between preoperative platelet count and function and its relationship with postoperative bleeding in cardiac surgery. Platelets. 2017;28:794–798. doi: 10.1080/09537104.2017.1280148 28277058

23. Li YG, Ni L, Brandt JT, Small DS, Payne CD, Ernest CS 2nd, et al. Inhibition of platelet aggregation with prasugrel and clopidogrel: an integrated analysis in 846 subjects. Platelets. 2009;20:316–327. doi: 10.1080/09537100903046317 19637095

24. Rath CL, Rye Jørgensen N, Wienecke T. High On-Treatment Platelet Reactivity in Danish hyper-acute ischaemic stroke patients. Front Neurol. 2018;9:712. doi: 10.3389/fneur.2018.00712 30210437

25. Musallam A, Orvin K, Perl L, Mosseri M, Arbel Y, Roguin A, et al. Effect of modifying antiplatelet treatment to Ticagrelor in high-risk coronary patients with low response to Clopidogrel (MATTIS). Can J Cardiol. 2016;32:1246.e13–1246.e1

26. Lemesle G, Schurtz G, Bauters C, Hamon M. High on-treatment platelet reactivity with ticagrelor versus prasugrel: a systematic review and meta-analysis. J Thromb Haemost. 2015;13:931–942. doi: 10.1111/jth.12907 25809392

27. Bavishi C, Panwar S, Messerli FH, Bangalore S. Meta-analysis of comparison of the newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2015;116:809–817. doi: 10.1016/j.amjcard.2015.05.058 26119655

28. Jastrzebska M, Marcinowska Z, Oledzki S, Chelstowski K, Siennicka A, Klysz M, et al. Variable gender-dependent platelet responses to combined antiplatelet therapy in patients with stable coronary-artery disease. J Physiol Pharmacol 2018; 69; ePaub ahead of print.

29. Sowers MR, Matthews KA, Jannausch M, Randolph JF, McConnell D, Sutton-Tyrrell K, et al. Hemostatic factors and estrogen during the menopausal transition. J Clin Endocrinol Metab. 2005;90:5942–5948. doi: 10.1210/jc.2005-0591 16105968

30. Caulin-Glaser T, Garcia-Cardena G, Sarrel P, SessaWC,Bender JR. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res. 1997;81:885–892. doi: 10.1161/01.res.81.5.885 9351464

31. Williams ET, Leyk M, Wrighton SA, Davies PJA, Loose DS, Shipley GL, et al. Estrogen regulation of the Cytochrome P450 3A subfamily in humans. J Pharmacol Exp Ther. 2004;311:728–735. doi: 10.1124/jpet.104.068908 15282264

32. Al-Husein BA, Al-Azzam SI, Alzoubi KH, Khabour OF, Nusair MB, Alzayadeen S. Investigating the effect of demographics, clinical characteristics, and polymorphism of MDR-1, CYP1A2, CYP3A4, and CYP3A5 on clopidogrel resistance. J Cardiovasc Pharmacol. 2018;72:296–302. doi: 10.1097/FJC.0000000000000627 30422888


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