Platelet function and response to aspirin: Gender-specific features and implications for female thrombotic risk and management

Seminars in Thrombosis and Hemostasis

Volumn 35, Issue 3, 2009, Pages 295-306

  Zuern, Christine S ^a,b   Lindemann, Stephan ^a   Gawaz, Meinrad ^a  

^a Medizinische Klinik III   (Germany)

^b Abteilung III   (Germany)

Author keywords

Aspirin; Coronary artery disease; Platelets; Sex differences; Women

Indexed keywords

ACETYLSALICYLIC ACID; CLOPIDOGREL; CYCLOOXYGENASE 1; PLACEBO; SEX HORMONE; ANTITHROMBOCYTIC AGENT;

ATHEROSCLEROSIS; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DISTRIBUTION VOLUME; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG MECHANISM; HEART INFARCTION; HORMONE ACTION; HUMAN; HYPERTENSION; LOW DRUG DOSE; MORTALITY; NONHUMAN; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; SEX DIFFERENCE; THROMBOCYTE AGGREGATION; THROMBOCYTE COUNT; THROMBOCYTE FUNCTION; THROMBOSIS; TREATMENT RESPONSE; AGE; ANIMAL; BLOOD; DRUG EFFECT; FEMALE; MALE; PHYSIOLOGY; RISK FACTOR;

AGE FACTORS; ANIMALS; ASPIRIN; CLINICAL TRIALS AS TOPIC; FEMALE; GONADAL STEROID HORMONES; HUMANS; MALE; MYOCARDIAL INFARCTION; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; RISK FACTORS; SEX FACTORS; THROMBOSIS;

EID: 67649158641     PISSN: 00946176     EISSN: 10989064     Source Type: Journal    
DOI: 10.1055/s-0029-1222608     Document Type: Review

References (97)

1. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005;352:1293-1304
2. Hansson L, Zanchetti A, Carruthers SG, et al; HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-1762
3. de Gaetano G; Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 2001;357:89-95
4. Kjeldsen SE, Kolloch RE, Leonetti G, et al. Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment. J Hypertens 2000; 18:629-642 (Pubitemid 30303495)
5. Steering Committee of the Physicians' Health Study Research Group. Final report on the aspirin component of the ongoing Physicians Health Study. N Engl J Med 1989; 321:129-135
6. Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988;296:313-316 (Pubitemid 18042841)
7. The Medical Research Council's General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998;351:233-241
8. Gattellari M, Worthington J, Zwar N. Warfarin: an inconvenient truth. Stroke 2009;40:5-7
9. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med 1999;341:217-225
10. Hochman JS, Tamis JE, Thompson TD, et al. Sex, clinical presentation and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. N Engl J Med 1999;341:226-232
11. Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature 1975;253:355-357
12. Stevens RF, Alexander MK. A sex difference in the platelet count. Br J Haematol 1977;37:295-300
13. Zwierzina WD, Kunz F, Kogelnig R, Herold M. Sex-related differences in platelet aggregation in native whole blood. Thromb Res 1987;48:161-171 (Pubitemid 18050943)
14. Kelton JG, Carter CJ, Santos A, Hirsh J. Sex related differences in platelet function: the effect of aspirin. Blood 1982;59:625-627 (Pubitemid 12187484)
15. Harrison MJ, Weisblatt E. A sex difference in the effect of aspirin on "spontaneous" platelet aggregation in whole blood. Thromb Haemost 1983;50:773-774
16. Kurrelmeyer K, Becker L, Becker D, Yanek L, Goldschmidt-Clermont P, Bray PF. Platelet hyperreactivity in women from families with premature atherosclerosis. J Am Med Womens Assoc 2003;58:272-277
17. Leng XH, Hong SY, Larrucea S, et al. Platelets of female mice are intrinsically more sensitive to agonists than are platelets of males. Arterioscler Thromb Vasc Biol 2004; 24:376-381 (Pubitemid 38197593)
18. Meade TW, Vickers MV, Thompson SG, Stirling Y, Haines AP, Miller GJ. Epidemiological characteristics of platelet aggregability. Br Med J (Clin Res Ed) 1985;290:428-432
19. Faraday N, Goldschmidt-Clermont PJ, Bray PF. Gender differences in platelet GPIIb-IIIa activation. Thromb Haemost 1997;77:748-754 (Pubitemid 27182975)
20. Becker DM, Segal J, Vaidya D, et al. Sex differences in platelet reactivity and response to low-dose aspirin therapy. JAMA 2006;295:1420-1427
21. Ivandic BT, Giannitsis E, Schlick P, Staritz P, Katus HA, Hohlfeld T. Determination of aspirin responsiveness by use of whole blood platelet aggregometry. Clin Chem 2007;53: 614-619 (Pubitemid 46580230)
22. Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost 2008;34:709-733
23. Favaloro EJ. Clinical application of the PFA-100. Curr Opin Hematol 2002;9:407-415
24. Favaloro EJ. The utility of the PFA-100 in the identification of von Willebrand disease: a concise review. Semin Thromb Hemost 2006;32:537-545 (Pubitemid 44157393)
25. Favaloro EJ. Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA-100® and von Willebrand factor collagen-binding activity as coupled strategies. Semin Thromb Hemost 2006;32:566-576
26. Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an in vitro platelet function analyzer - PFA-100. Semin Thromb Hemost 1995; 21(Suppl 2):106-112
27. Cho YU, Jang S, Park CJ, Chi HS. Variables that affect platelet function analyzer-100 (PFA-100) closure times and establishment of reference intervals in Korean adults. Ann Clin Lab Sci 2008;38:247-253
28. Böck M, De Haan J, Beck KH, et al. Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives. Br J Haematol 1999;106:898-904 (Pubitemid 29463001)
29. Sestito A, Sciahbasi A, Landolfi R, Maseri A, Lanza GA, Andreotti F. A simple assay for platelet-mediated hemostasis in flowing whole blood (PFA-100): reproducibility and effects of sex and age. Cardiologia 1999;44:661-665
30. Haubelt H, Anders C, Vogt A, Hoerdt P, Seyfert UT, Hellstern P. Variables influencing Platelet Function Analyzer-100 closure times in healthy individuals. Br J Haematol 2005;130:759-767 (Pubitemid 43906649)
31. Porto I, Leone AM, Nanni L, et al. Interplay of platelet polymorphisms, risk factors, and von Willebrand factor in determining collagen-adenosine diphosphate PFA-100 results in patients with coronary artery disease. Blood Coagul Fibrinolysis 2005;16:97-104 (Pubitemid 40418587)
32. Cho YU, Chi HS, Jang S, Park CJ. [Reconfirmation of preanalytical variables and establishment of reference intervals of platelet function analyzer-100 closure times in Korean adults]. Korean J Lab Med 2007;27:318-323
33. Brockmann MA, Beythien C, Magens MM, Wilckens V, Kuehnl P, Gutensohn K. Platelet hemostasis capacity in smokers. In vitro function analyses with 3.2% citrated whole blood. Thromb Res 2001;104:333-342
34. Kluft C, Lansink M. Effect of oral contraceptives on haemostasis variables. Thromb Haemost 1997;78:315-326 (Pubitemid 27289261)
35. Crescente M, Di Castelnuovo A, Iacoviello L, Vermylen J, Cerletti C, de Gaetano G. Response variability to aspirin as assessed by the platelet function analyzer (PFA)-100. A systematic review. Thromb Haemost 2008;99:14-26 (Pubitemid 351705320)
36. Gum PA, Kottke-Marchant K, Poggio ED, et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001;88:230-235 (Pubitemid 32721947)
37. Abaci A, Caliskan M, Bayram F, et al. A new definition of aspirin non-responsiveness by platelet function analyzer-100 and its predictors. Platelets 2006;17:7-13 (Pubitemid 41759235)
38. Pamukcu B, Oflaz H, Onur I, et al. Aspirin-resistant platelet aggregation in a cohort of patients with coronary heart disease. Blood Coagul Fibrinolysis 2007;18:461-465 (Pubitemid 46975949)
39. Hayward CP, Harrison P, Cattaneo M, Ortel TL, Rao A; KThe Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006;4:312-319
40. Smith SC Jr, Allen J, Blair SN, et al; AHA/ACCNational Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006;113:2363-2372
41. Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med 2002;162:2197-2202
42. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40 000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. On behalf of the CAST and IST collaborative groups. Stroke 2000;31:1240-1249 (Pubitemid 30351240)
43. Maree AO, Fitzgerald DJ. Aspirin and coronary artery disease. Thromb Haemost 2004;92:1175-1181
44. Schrör K. Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis. Semin Thromb Hemost 1997;23:349-356 (Pubitemid 27360075)
45. Schafer AI. Antiplatelet therapy. Am J Med 1996;101:199-209
46. Mousa SA, Forsythe MS, Bozarth JM, Reilly TM. Effect of single oral dose of aspirin on human platelet functions and plasma plasminogen activator inhibitor-1. Cardiology 1993; 83:367-373
47. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86
48. Antiplatelet Trialists' Collaboration. Collaborative overview of randomized trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106
49. ISIS-2 (Second international Study of Infarct Survival) collaborative group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988;2:349-360
50. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86
51. Becker RC, Meade TW, Berger PB, et al; American College of Chest Physicians. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6, Suppl):776S-814S
52. Wenger NK. Drugs for cardiovascular disease prevention in women: implications of the AHA Guidelines - 2007 Update. Drugs 2008;68:339-358
53. Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart 2001;85:265-271 (Pubitemid 32973555)
54. Mosca L, Appel LJ, Benjamin EJ, et al; American Heart Association. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004;109:672-693
55. Shafazand M, Schaufelberger M, Lappas G, Swedberg K, Rosengren A. Survival trends in men and women with heart failure of ischaemic and non-ischaemic origin: data for the period 1987-2003 from the Swedish Hospital Discharge Registry. Eur Heart J 2008; December 24 (Epub a head of print)
56. Barrett-Connor EL, Cohn BA, Wingard DL, Edelstein SL. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study JAMA 1991;265:627-631
57. O'Sullivan JB, Mahan CM. Mortality related to diabetes and blood glucose levels in a community study. Am J Epidemiol 1982;116:678-684 (Pubitemid 12037000)
58. Legrand DA, Scheen AJ. [Aspirin for primary prevention of cardiovascular diseases in diabetic patients: focus on gender difference and insulin resistance]. Rev Med Liege 2006; 61:682-690
59. Elsaesser A, Hamm CW. Acute coronary syndrome: the risk of being female. Circulation 2004;109:565-567 (Pubitemid 38198861)
60. Duvall WL, Vorchheimer DA. Multi-bed vascular disease and atherothrombosis: scope of the problem. J Thromb Thrombolysis 2004;17:51-61 (Pubitemid 39069462)
61. American Heart Association. Heart disease and stroke statistics - 2007 update. Available at: http://circ.ahajournals. org. Accessed June 29, 2007
62. Länne T, Ahlgren AR. Increased arterial stiffness in IDDM women - methodological considerations. Diabetologia 1996;39:871-872 (Pubitemid 26228122)
63. Hu J, Norman M, Wallensteen M, Gennser G. Increased large arterial stiffness and impaired acetylcholine induced skin vasodilatation in women with previous gestational diabetes mellitus. Br J Obstet Gynaecol 1998;105:1279-1287 (Pubitemid 29002829)
64. Pepine CJ, Kerensky RA, Lambert CR, et al. Some thoughts on the vasculopathy of women with ischemic heart disease. J Am Coll Cardiol 2006;47(3, Suppl):S30-S35
65. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med 1999;341:217-225
66. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J 1986;111:383-390
67. Marrugat J, Sala J, Masiá R, et al. Mortality differences between men and women following first myocardial infarction. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempo de Espera. JAMA 1998;280:1405-1409
68. Sanderson S, Emery J, Baglin T, Kinmonth AL. Narrative review: aspirin resistance and its clinical implications. Ann Intern Med 2005;142:370-380 (Pubitemid 40293410)
69. Berger JS, RoncaglioniMC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006; 295:306-313 (Pubitemid 43112959)
70. Manson JE, Stampfer MJ, Colditz GA, et al. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. JAMA 1991;266:521-527
71. Yerman T, Gan WQ, Sin DD. The influence of gender on the effects of aspirin in preventing myocardial infarction. BMC Med 2007;5:29 (Pubitemid 350269071)
72. Chen WH, Lee PY, Ng W, Tse HF, Lau CP. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004;43:1122-1126 (Pubitemid 38353000)
73. Mosca L, Banka CL, Benjamin EJ, et al; on behalf of the Expert Panel/Writing Group; American Academy of Physician Assistants; American Association for Clinical Chemistry; American Association of Cardiovascular and Pulmonary Rehabilitation; American College of Chest Physicians; American College of Emergency Physicians; American Diabetes Association; American Geriatrics Society; American Society for Preventive Cardiology; American Society of Echocardiography; American Society of Nuclear Cardiology; Association of Women's Health, Obstetric and Neonatal Nurses; Global Alliance for Women's Health; Mended Hearts, Inc; National Black Nurses Association; National Black Women's Health Imperative; National Women's Health Resource Center; North American Menopause Society; Partnership for Gender-Specific Medicine at Columbia University; Preventive Cardiovascular Nurses Association; Society for Vascular Medicine and Biology; Society for Women's Health Research; Society of Geriatric Cardiology; Women in Thoracic Surgery; WomenHeart: the National Coalition forWomen with Heart Disease. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol 2007;49:1230-1250
74. Buchanan MR, Rischke JA, Butt R, Turpie AG, Hirsh J, Rosenfeld J. The sex-related differences in aspirin pharmacokinetics in rabbits and man and its relationship to antiplatelet effects. Thromb Res 1983;29:125-139 (Pubitemid 13140093)
75. Ho PC, Triggs EJ, Bourne DW, Heazlewood VJ. The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. Br J Clin Pharmacol 1985;19:675-684 (Pubitemid 16255938)
76. Miners JO, Grgurinovich N, Whitehead AG, Robson RA, Birkett DJ. Influence of gender and oral contraceptive steroids on the metabolism of salicylic acid and acetylsalicylic acid. Br J Clin Pharmacol 1986;22:135-142
77. Ridker PM, Hennekens CH, Tofler GH, Lipinska I, Buring JE. Anti-platelet effects of 100 mg alternate day oral aspirin: a randomized, double-blind, placebo-controlled trial of regular and enteric coated formulations in men and women. J Cardiovasc Risk 1996;3:209-212 (Pubitemid 26266495)
78. Escolar G, Bastida E, Garrido M, Rodríguez-Gómez J, Castillo R, Ordinas A. Sex-related differences in the effects of aspirin on the interaction of platelets with subendothelium. Thromb Res 1986;44:837-847 (Pubitemid 17228885)
79. Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease. The Framingham Study. Ann Intern Med 1978;89:157-161
80. Rosenberg L, Hennekens CH, Rosner B, Belanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139: 47-51 (Pubitemid 11213576)
81. Leinwand LA. Sex is a potent modifier of the cardiovascular system. J Clin Invest 2003;112:302-307
82. Milcent C, Dormont B, Durand-Zaleski I, Steg PG. Gender differences in hospital mortality and use of percutaneous coronary intervention in acute myocardial infarction: microsimulation analysis of the 1999 nationwide French hospitals database. Circulation 2007;115:833-839
83. Manson JE, Hsia J, Johnson KC, et al; Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-534
84. Frederiksen H, Ravenholt RT. Thromboembolism, oral contraceptives, and cigarettes. Public Health Rep 1970;85: 197-205
85. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321-333
86. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000;132:689-696
87. Langer RD, Pradhan AD, Lewis CE, et al. Baseline associations between postmenopausal hormone therapy and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health Initiative Observational Study. Thromb Haemost 2005;93:1108-1116
88. Howard BV, Hsia J, Ouyang P, et al. Postmenopausal hormone therapy is associated with atherosclerosis progression in women with abnormal glucose tolerance. Circulation 2004;110:201-206 (Pubitemid 38924589)
89. Alexandersen P, Tankó LB, Bagger YZ, Qin G, Christiansen C. The long-term impact of 2-3 years of hormone replacement therapy on cardiovascular mortality and atherosclerosis in healthy women. Climacteric 2006;9:108-118
90. Pelzer T, Shamim A, Wölfges S, Schumann M, Neyses L. Modulation of cardiac hypertrophy by estrogens. Adv Exp Med Biol 1997;432:83-89
91. Grohe C, Briesmeister G, Stimpel L, Karas RH, Vetter H, Neyses L. Functional estrogen receptors in myocardial and myogenic cells. Circulation 1994;90:I-538
92. Grohé C, Kahlert S, Löbbert K, et al. Modulation of hypertensive heart disease by estrogen. Steroids 1996;61:201-204 (Pubitemid 26144423)
93. Klein-Hitpass L, Schorpp M, Wagner U, Ryffel GU. An estrogen-responsive element derived from the 5′ flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell 1986;46:1053-1061 (Pubitemid 17182729)
94. Grohé C, Kahlert S, Löbbert K, et al. Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett 1997;416:107-112 (Pubitemid 27470812)
95. Spranger M, Aspey BS, Harrison MJ. Sex difference in antithrombotic effect of aspirin. Stroke 1989;20:34-37 (Pubitemid 19040210)
96. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007;297:2018-2024 (Pubitemid 46740354)
97. Rumilla K, Chen D, Baudhuin LM. Pharmacogenetics in hemostasis: friend or foe? Semin Thromb Hemost 2009;35: 42-49