Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

1. Vögtle T, Cherpokova D, Bender M, Nieswandt B. Targeting platelet receptors in thrombotic and thrombo-inflammatory disorders. Hamostaseologie. 2015;35 [Epub ahead of print]10.5482/HAMO-14-10-004925634564Search in Google Scholar

2. Floyd CN, Ferro A. Anti-platelet drug resistance: Molecular insights and clinical implications. Prostaglandins Other Lipid Mediat. 2015; [Epub ahead of print]10.1016/j.prostaglandins.2015.03.01125868910Search in Google Scholar

3. Vlachojannis GJ, Dimitropoulos G, Alexopoulos D. Clopidogrel resistance: current aspects and future directions. Hell J Cardiol. 2011;52:236-45.Search in Google Scholar

4. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ ACC Guideline for the Management of Patients With Non- ST-Elevation Acute Coronary Syndromes. J Am Coll Cardiol. 2014;64:e139-228.10.1016/j.jacc.2014.09.01725260718Search in Google Scholar

5. Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569-619.10.1093/eurheartj/ehs21522922416Search in Google Scholar

6. Pyrgakis VN, Goudevenos JA. Clopidogrel and cardiovascular diseases: recommendations for its correct use. Hell J Cardiol. 2010;51:83-6.Search in Google Scholar

7. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49:1505-16.10.1016/j.jacc.2006.11.04417418288Search in Google Scholar

8. Papathanasiou A, Goudevenos J TAD. Resistance to Aspirin and Clopidogrel: Possible Mechanisms, Laboratory Investigation, and Clinical Significance. Hell J Cardiol. 2007;48:352-63.Search in Google Scholar

9. Dupont AG, Gabriel DA, Cohen MG. Anti-platelet therapies and the role of anti-platelet resistance in acute coronary syndrome. Thromb Res. 2009;124:6-13.10.1016/j.thromres.2009.01.01419324398Search in Google Scholar

10. Abacı O, Kılıçkesmez KO. Aspirin resistance: Where are we now? Anadolu Kardiyol Derg. 2013;13:370-3.Search in Google Scholar

11. Karaźniewicz-Łada M, Danielak D, Główka F. Genetic and nongenetic factors affecting the response to clopidogrel therapy. Expert Opin Pharmacother. 2012;13:663-83.10.1517/14656566.2012.66652422397459Search in Google Scholar

12. Abbate R, Crea F, De Servi S, et al. [Extent of platelet aggregation inhibition and clinical events: new evidence with prasugrel]. G Ital Cardiol. 2010;11:127-37.Search in Google Scholar

13. Fileti L, Campo G, Valgimigli M. Latest clinical data on testing for high on-treatment platelet reactivity. Rev Cardiovasc Med. 2011;12(Suppl 1):S14-22.10.3909/ricm12S1S0001Search in Google Scholar

14. Saraf S, Bensalha I, Gorog DA. Anti-platelet Resistance - Does it Exist and How to Measure it ? Clin Med Cardiol. 2009;3:77-91.Search in Google Scholar

15. Ahluwalia K, Bhanwra S. Anti-platelet therapy: present status and its future directions. Int J Basic Clin Pharmacol. 2014;3:260.10.5455/2319-2003.ijbcp20140402Search in Google Scholar

16. Patrono C, Coller B, FitzGerald G A., Hirsh J, Roth G. Plateletactive drugs: The relationships among dose, effectiveness, and side effects - The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Supl).10.1378/chest.126.3_suppl.234S15383474Search in Google Scholar

17. Bagoly Z, Sarkady F, Magyar T, et al. Comparison of a New P2Y12 Receptor Specific Platelet Aggregation Test with Other Laboratory Methods in Stroke Patients on Clopidogrel Monotherapy. PLoS One. 2013;8:1-11.10.1371/journal.pone.0069417Search in Google Scholar

18. Huang B, Huang Y, Li Y, et al. Adverse cardiovascular effects of concomitant use of proton pump inhibitors and clopidogrel in patients with coronary artery disease: a systematic review and meta-analysis. Arch Med Res. 2012;43:212-24.10.1016/j.arcmed.2012.04.004Search in Google Scholar

19. Bonello L, Tantry US, Marcucci R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919-33.10.1016/j.jacc.2010.04.047Search in Google Scholar

20. Mallouk N, Labruyère C, Reny J-L, et al. Prevalence of poor biological response to clopidogrel: a systematic review. Thromb Haemost. 2012;107:494-506.10.1160/TH11-03-0202Search in Google Scholar

21. Aradi D, Komócsi A, Vorobcsuk A, et al. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J. 2010;160:543-51.10.1016/j.ahj.2010.06.004Search in Google Scholar

22. Combescure C, Fontana P, Mallouk N, et al. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost. 2010;8:923-33.10.1111/j.1538-7836.2010.03809.xSearch in Google Scholar

23. Sofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF. Clopidogrel non-responsiveness and risk of cardiovascular morbidity: An updated meta-analysis. Thromb Haemost. 2010;103:841-8.Search in Google Scholar

24. Brar SS, Ten Berg J, Marcucci R, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011;58:1945-54.10.1016/j.jacc.2011.06.059Search in Google Scholar

25. Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet. 2006;367:606-17.10.1016/S0140-6736(06)68040-9Search in Google Scholar

26. Topçuoglu MA, Arsava EM, Ay H. Anti-platelet resistance in stroke. Expert Rev Neurother. 2011;11:251-63.10.1586/ern.10.203308667321306212Search in Google Scholar

27. Schwartz KA, Schwartz DE, Barber K, Reeves M, De Franco AC. Non-compliance is the predominant cause of aspirin resistance in chronic coronary arterial disease patients. J Transl Med. 2008;6:46.10.1186/1479-5876-6-46253850118759978Search in Google Scholar

28. Serebruany V, Cherala G, Williams C, et al. Association of platelet responsiveness with clopidogrel metabolism: role of compliance in the assessment of “resistance”. Am Heart J. 2009;158:925-32.10.1016/j.ahj.2009.10.012Search in Google Scholar

29. Herlitz J, Tóth PP, Naesdal J. Low-dose aspirin therapy for cardiovascular prevention: quantification and consequences of poor compliance or discontinuation. Am J Cardiovasc Drugs. 2010;10:125-41.10.2165/11318440-000000000-00000Search in Google Scholar

30. Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation. 2013;127:377-85.10.1161/CIRCULATIONAHA.112.117283Search in Google Scholar

31. Feher G, Feher A, Pusch G, et al. Clinical importance of aspirin and clopidogrel resistance. World J Cardiol. 2010;2:171-86.10.4330/wjc.v2.i7.171Search in Google Scholar

32. Mansour K, Taher AT, Musallam KM, Alam S. Aspirin resistance. Adv Hematol. 2009;2009:1-10.10.1155/2009/937352Search in Google Scholar

33. Scott SA, Owusu Obeng A, Hulot J-S. Anti-platelet drug interactions with proton pump inhibitors. Expert Opin Drug Metab Toxicol. 2014;10:175-89.10.1517/17425255.2014.856883Search in Google Scholar

34. Johnson DA, Chilton R, Liker HR. Proton-pump inhibitors in patients requiring anti-platelet therapy: new FDA labeling. Postgrad Med. 2014;126:239-45.10.3810/pgm.2014.05.2772Search in Google Scholar

35. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:713-8.10.1503/cmaj.082001Search in Google Scholar

36. Stockl KM. Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor. Arch Intern Med. 2010;170:704.10.1001/archinternmed.2010.34Search in Google Scholar

37. Neubauer H, Günesdogan B, Hanefeld C, Spiecker M, Mügge A. Lipophilic statins interfere with the inhibitory effects of clopidogrel on platelet function - A flow cytometry study. Eur Heart J. 2003;24:1744-9.10.1016/S0195-668X(03)00442-1Search in Google Scholar

38. Park Y, Jeong Y-H, Tantry US, et al. Accelerated platelet inhibition by switching from atorvastatin to a non-CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study. Eur Heart J. 2012;33:2151-62.10.1093/eurheartj/ehs08322507978Search in Google Scholar

39. Pelliccia F, Rosano G, Marazzi G, et al. Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual anti-platelet therapy. Circ J. 2014;78:679-84.10.1253/circj.CJ-13-1216Search in Google Scholar

40. Hedegaard SS, Hvas A-M, Grove EL, et al. Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration. Thromb Res. 2009;124:96-100.10.1016/j.thromres.2008.12.03419215971Search in Google Scholar

41. Ojeifo O, Wiviott SD, Antman EM, et al. Concomitant administration of clopidogrel with statins or calcium-channel blockers: insights from the TRITON-TIMI 38 (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarctio. JACC Cardiovasc Interv. 2013;6:1275-81.10.1016/j.jcin.2013.06.01424239201Search in Google Scholar

42. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000;55:843-52.10.1007/s00228005070610805063Search in Google Scholar

43. Seo K-D, Kim YD, Yoon Y-W, Kim J-Y, Lee K-Y. Anti-platelet effect of clopidogrel can be reduced by calcium-channel blockers. Yonsei Med J. 2014;55:683-8.10.3349/ymj.2014.55.3.683399009824719135Search in Google Scholar

44. Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E. The genetics of anti-platelet drug resistance. Clin Genet. 2009;75:1-18.10.1111/j.1399-0004.2008.01105.x19067731Search in Google Scholar

45. Goodman T, Ferro A, Sharma P. Pharmacogenetics of aspirin resistance: A comprehensive systematic review. Br J Clin Pharmacol. 2008;66: 222-32.10.1111/j.1365-2125.2008.03183.x249291318429969Search in Google Scholar

46. Altman R, Flockhart D, Goldstein D. Principles of pharmacogenetics and pharmacogenomics. 1st ed. 2012;121-4.10.1017/CBO9781139051194Search in Google Scholar

47. Negovan A, Voidăzan S, Pantea M, et al. AGT A-20C (rs5050) gene polymorphism and ulcer occurrence in patients treated with low-dose aspirin: a case-control study. Rev Romana Med Lab. 2015;23:179-87.Search in Google Scholar

48. Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. 2010;38:92-9.10.1124/dmd.109.02913219812348Search in Google Scholar

49. Kim KA, Park PW, Hong SJ, Park J-Y. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008;84:236-42.10.1038/clpt.2008.2018323861Search in Google Scholar

50. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 Polymorphisms and Response to Clopidogrel. N Engl J Med. 2009;360:354-62.10.1056/NEJMoa080917119106084Search in Google Scholar

51. Varenhorst C, James S, Erlinge D, et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirintreated patients with coronary artery disease. Eur Heart J. 2009;30:1744-52.10.1093/eurheartj/ehp157270988519429918Search in Google Scholar

52. Simon T, Céline V, Murielle M-K, et al. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. N Engl J Med. 2009;360:363-75.10.1056/NEJMoa080822719106083Search in Google Scholar

53. Seip RL, Duconge J, Ruaño G. Implementing genotype-guided antithrombotic therapy. Future Cardiol. 2010;6:409-24.10.2217/fca.10.6290322920462345Search in Google Scholar

54. Militaru FC, Vesa ŞC, Crişan S, Militaru V, Trifa AP, Buzoianu AD. Genotype-phenotype correlations in patients treated with acenocoumarol. Rev Romana Med Lab. 2014;22:347-54.Search in Google Scholar

55. Limdi NA, Wiener H, Goldstein JA, Acton RT, Beasley TM. Influence of CYP2C9 and VKORC1 on warfarin response during initiation of therapy. Blood Cells Mol Dis. 2009;43:119-28.10.1016/j.bcmd.2009.01.019278974119297219Search in Google Scholar

56. Michelson AD, Cattaneo M, Eikelboom JW, Gurbel P. Aspirin resistance: position paper of the Working Group on Aspirin Resistance. Haemostasis. 2005;3:1309-11.10.1111/j.1538-7836.2005.01351.x15892858Search in Google Scholar

57. Gasparyan AY, Watson T, Lip GYH. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol. 2008;51:1829-43.10.1016/j.jacc.2007.11.08018466797Search in Google Scholar

58. Nguyen NQ, Chapman MJ, Fraser RJ, et al. The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness. Intensive Care Med. 2008;34:454-60.10.1007/s00134-007-0942-218060542Search in Google Scholar

59. Hong J-Y, Oh JI. Effects of preoperative anxiety on gastric fluid acidity and volume. J Korean Med Sci. 2005; 20:232-5.10.3346/jkms.2005.20.2.232280859815831993Search in Google Scholar

60. Roush J a. The role of the stomach in drug absorption as observed via absorption rate analysis. Int J Pharm. 2014;471:112-7.10.1016/j.ijpharm.2014.05.01824853462Search in Google Scholar

61. Ganesan S, Williams C, Maslen CL, Cherala G. Clopidogrel variability: role of plasma protein binding alterations. Br J Clin Pharmacol. 2013;75:1468-77.10.1111/bcp.12017369010523116430Search in Google Scholar

62. Storm C, Schefold JC, Kerner T, et al. Prehospital cooling with hypothermia caps (PreCoCa): A feasibility study. Clin Res Cardiol. 2008;97:768-72.10.1007/s00392-008-0678-118512093Search in Google Scholar

63. Bjelland TW, Hjertner Ø, Klepstad P, Kaisen K, Dale O, Haugen BO. Anti-platelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation. 2010;81:1627-31.10.1016/j.resuscitation.2010.07.00220727659Search in Google Scholar

64. Součková L, Opatřilová R, Suk P, et al. Impaired bioavailability and anti-platelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). Eur J Clin Pharmacol. 2013;69:309-17.10.1007/s00228-012-1360-022890586Search in Google Scholar

65. Ogu CC, Maxa JL. Drug interactions due to cytochrome P450. Proc (Bayl Univ Med Cent). 2000;13:421-3.Search in Google Scholar

66. Pascoe MC, Howells DW, Crewther DP, et al. Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment. Front Neurol. 2014;5:14.10.3389/fneur.2014.00014391523924567728Search in Google Scholar

67. Wachira JK, Larson MK, Harris WS. n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights. Br J Nutr. 2014;111:1652-62.10.1017/S000711451300425X24472372Search in Google Scholar

68. Bradnam V, White R. Handbook of Drug Administration Via Enteral Feeding Tubes, 3rd edition, London, UK: Pharmaceutical Press; 2015.Search in Google Scholar

69. Powers JE, Cascella PJ. Comparison of methods used to prepare tablets for nasogastric tube administration. J Pharm Technol. 1990;6:60-2.10.1177/875512259000600209Search in Google Scholar

70. Patel V, Kukadiya H, Mashru R, Surti N, Mandal S. Development of microemulsion for solubility enhancement of clopidogrel. Iran J Pharm Res IJPR. 2010;9:327-34.Search in Google Scholar

71. Lenk E, Spannagl M. Platelet function testing - guided antiplatelet therapy. J Int Fed Clin Chem Lab Med. 2013;24:1-7.Search in Google Scholar

72. Breet NJ, Werkum JW van, Bouman HJ, et al. Comparison of Platelet Function Tests Undergoing Coronary Stent Implantation. JAMA. 2010;303:754-62.10.1001/jama.2010.18120179285Search in Google Scholar

73. Paniccia R. Assessment of platelet function: Laboratory and point-of-care methods. World J Transl Med. 2014;3:69.10.5528/wjtm.v3.i2.69Search in Google Scholar

74. Gladding P, Webster M, Ormiston J, Olsen S, White H. Antiplatelet drug nonresponsiveness. Am Heart J. 2008;155:591-9.10.1016/j.ahj.2007.12.03418371464Search in Google Scholar

75. Tousoulis D, Siasos G, Stefanadis C. Aspirin resistance: what the cardiologist needs to know? Int J Cardiol. 2009;132:153-6.Search in Google Scholar

76. Michelson AD. Platelets. 2nd ed. 2007;545-63.10.1016/B978-012369367-9/50792-8Search in Google Scholar

77. Gachet C, Aleil B. Testing anti-platelet therapy. Eur Hear J Suppl. 2008;10(Suppl A):A28-34.10.1093/eurheartj/sum081Search in Google Scholar

78. Harrison P. The role of PFA-100 testing in the investigation and management of haemostatic defects in children and adults. Br J Haematol. 2005;130:3-10.10.1111/j.1365-2141.2005.05511.x15982339Search in Google Scholar

79. Hayward CPM, Harrison P, Cattaneo M, Ortel TL, Rao AK. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost. 2006;4:312-9.10.1111/j.1538-7836.2006.01771.x16420557Search in Google Scholar

80. Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost. 2008;34:709-33.10.1055/s-0029-114525419214910Search in Google Scholar

81. Hussein HM, Emiru T, Georgiadis AL, Qureshi AI. Assessment of platelet inhibition by point-of-care testing in neuroendovascular procedures. Am J Neuroradiol. 2013;34:700-6.10.3174/ajnr.A2963796447622422188Search in Google Scholar

82. Aradi D, Storey RF, Komócsi A, et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2014;35:209-15.10.1093/eurheartj/eht375389686124067509Search in Google Scholar

83. Meybohm P, Zacharowski K, Weber CF. Point-of-care coagulation management in intensive care medicine. Crit Care. 2013;17:218.10.1186/cc12527367263423510484Search in Google Scholar

84. Adamzik M, Gorlinger K, Peters J, Hartmann M. Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis. Crit Care. 2012;16:R204.10.1186/cc11816368230723088388Search in Google Scholar

85. Short S, Kram B, Taylor S, Cheng J, Ali K, Vasquez D. Effect of platelet inhibition on bleeding complications in trauma patients on preinjury clopidogrel. J Trauma Acute Care Surg. 2013;74:1419-24.10.1097/TA.0b013e31828dac3e23694867Search in Google Scholar

86. Clareus A, Fredriksson I, Wallén H, Gordon M, Stark A, Sköldenberg O. Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients. World J Orthop. 2015;6:439-45.10.5312/wjo.v6.i5.439445849526085986Search in Google Scholar

87. Rosengart TK, Romeiser JL, White LJ, et al. Platelet activity measured by a rapid turnaround assay identifies coronary artery bypass grafting patients at increased risk for bleeding and transfusion complications after clopidogrel administration. J Thorac Cardiovasc Surg. 2013;146:1259-66, 1266.e1; discussion 1266.Search in Google Scholar

88. Mishra P, Thekkudan J, Sahajanandan R, et al. The role of point-of-care assessment of platelet function in predicting postoperative bleeding and transfusion requirements after coronary artery bypass grafting. Ann Card Anaesth. 2015;18:45.10.4103/0971-9784.148321490032725566711Search in Google Scholar

89. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009;53:849-56. 10.1016/j.jacc.2008.11.03019264241Search in Google Scholar