This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Michelson, A. D. Search for Related Content PubMed PubMed Citation Articles by Michelson, A. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID Related Collections Arterial thrombosis Platelet function inhibitors Thrombosis risk factors Other Treatment Other diagnostic testing Antiplatelets Platelets Related Article

(Circulation. 2004;110:e489-e493.)
© 2004 American Heart Association, Inc.

Clinician Update

Platelet Function Testing in Cardiovascular Diseases

Alan D. Michelson, MD

From the Center for Platelet Function Studies, Departments of Pediatrics, Medicine, and Pathology, University of Massachusetts Medical School, Worcester, Mass.

Correspondence to Alan D. Michelson, MD, Director, Center for Platelet Function Studies, Room S5-846, 55 Lake Ave N, Worcester, MA 01655. E-mail michelson{at}platelets.org

	Introduction

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
Case presentation 1: Mr F. is a 60-year-old man with unstable angina who takes aspirin, 81 mg/day. A platelet function test demonstrates that his platelets are "resistant" to aspirin. Should his treatment be changed?

Case presentation 2:Mr K. is a 60-year-old man with unstable angina who takes aspirin, 81 mg/day, and clopidogrel, 75 mg/day. A platelet function test demonstrates that his platelets are "resistant" to clopidogrel. Should his treatment be changed?

	Normal Platelet Function

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
Platelets are small cells of great importance in thrombosis, hemorrhage, and inflammation.¹ Formation of the hemostatic plug at sites of vascular injury is described in Figure 1. Platelets localize, amplify, and sustain the coagulant response at the injury site and release procoagulant platelet-derived microparticles. Platelets contain a variety of inflammatory modulators (eg, CD40 ligand [CD40L]) that are released on platelet activation.

View larger version (28K): [in this window] [in a new window]   Figure 1. Steps in platelet plug formation. A, Before vascular injury, platelets are maintained in a resting state by endothelial inhibitory factors: prostacyclin (PGI2), nitric oxide (NO), and CD39. B, The platelet plug is initiated by the exposure of collagen and the local generation of thrombin. This causes platelets to adhere via collagen and von Willebrand factor (vWF) and spread. C, The platelet plug is extended as additional platelets are activated via the release of thromboxane A2 (TxA2), ADP, and other platelet agonists. Platelet-to-platelet aggregation is mediated primarily by activation of the platelet surface GP IIb/IIIa (integrin IIbß3; not shown). D, A fibrin meshwork helps to perpetuate and stabilize the platelet aggregate. Reprinted from reference 2 with permission from Elsevier.

	Platelet Function Testing in Cardiovascular Diseases

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
Platelets have an increasingly well-defined critical role in coronary artery thrombosis³ and in other common cardiovascular diseases, including stroke, peripheral vascular disease, and diabetes mellitus.¹ Although the role of platelets in thrombosis is well characterized, platelets may also have a role in the pathogenesis of the underlying atherosclerotic process.³ Platelet function tests have been studied in cardiovascular disease as a means to predict clinical outcomes and to monitor antiplatelet drugs. Table 1 summarizes these tests.

View this table: [in this window] [in a new window]   TABLE 1. Platelet Function Tests in Cardiovascular Disease

	Use of Platelet Function Tests to Predict Clinical Outcomes

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
In acute coronary syndromes and after coronary stenting, flow cytometric analysis of platelet activation–dependent markers predicts major adverse cardiac events (MACE).⁵ Increased platelet surface P-selectin is also a risk factor for silent cerebral infarction in patients with atrial fibrillation.⁶ However, circulating monocyte–platelet aggregates are a more sensitive marker of in vivo platelet activation than is platelet surface P-selectin in the clinical settings of stable coronary artery disease,⁷ human percutaneous coronary intervention,⁸ and acute myocardial infarction.⁸ Furthermore, circulating monocyte–platelet aggregates are an early marker of acute myocardial infarction.⁹ Measurement of plasma CD40L in the first 12 hours after the onset of ischemic symptoms in patients with unstable angina identifies a subgroup of patients that gains a much greater clinical benefit from abciximab treatment.¹⁰ High plasma concentrations of sCD40L may be associated with increased cardiovascular risk in apparently healthy women.¹¹ In patients with stable angina, the Platelet Function Analyzer-100 (PFA-100; Dade Behring) closure time may predict the presence or absence of coronary artery stenoses at angiography, thereby potentially avoiding further diagnostic investigations.¹² PFA-100 closure time may also be predictive of the severity of myocardial damage in acute myocardial infarction.¹³ In summary, although a number of studies have demonstrated that platelet function tests can predict MACE in cardiovascular diseases, none of these assays have been sufficiently studied in large clinical trials to become part of standard clinical care.

	Use of Platelet Function Tests to Monitor Antiplatelet Drugs

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
Aspirin reduces the odds of a serious arterial thrombotic event in high-risk patients by 25%.¹⁴ However, 10% to 20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term follow-up.¹⁴ The failure of aspirin to prevent an arterial thrombotic event has been termed aspirin resistance. The failure of clopidogrel to prevent an arterial thrombotic event has been termed clopidogrel resistance. Similarly, the term GP IIb/IIIa antagonist resistance could be used. Because arterial thrombosis is multifactorial, an adverse arterial thrombotic outcome in a patient may often reflect treatment failure rather than resistance to an antiplatelet drug. Furthermore, patient noncompliance with aspirin, clopidogrel, or both is a frequent and hard-to-detect confounding problem. There is well-documented variability between patients (and "normal" volunteers) with regard to laboratory test responses to aspirin,^15–20 thienopyridines,²¹ and GP IIb/IIIa antagonists.²² This variability in laboratory test response has also been termed "resistance" to antiplatelet agents. The key question is: Do laboratory tests of resistance to aspirin, clopidogrel, or GP IIb/IIIa antagonists predict clinical resistance to these drugs (ie, MACE)? Clinically meaningful definitions of aspirin, clopidogrel, and GP IIb/IIIa antagonist resistance can be based only on data linking drug-dependent laboratory tests to clinical outcomes in patients. Until such links are clearly established, MACE that occur despite an antiplatelet agent should not be termed drug resistance.

Aspirin
Aspirin irreversibly acetylates serine 530 of cyclooxygenase-1 (COX-1), resulting in the inhibition of thromboxane A₂ release from platelets and prostacyclin from endothelial cells. Because platelets lack the synthetic machinery to generate significant amounts of new COX, aspirin-induced COX-1 inhibition lasts for the lifetime of the platelet. In contrast, endothelial cells retain their capacity to generate new COX and recover normal function shortly after exposure to aspirin. Possible mechanisms of aspirin resistance are listed in Table 2. There is evidence that MACE in the settings of acute coronary syndromes, stroke/transient ischemic attacks, and peripheral arterial disease can be predicted by the following in vitro tests of aspirin resistance: arachidonic acid– and ADP-induced platelet aggregation (turbidometric), ADP- and collagen-induced platelet aggregation (impedance), VerifyNow (Accumetrics), PFA-100, or urinary 11-dehydrothromboxane B₂ (Figure 2A).^15–20 However, in all of these studies, the number of MACE was low.

View this table: [in this window] [in a new window]   TABLE 2. Possible Mechanisms of Aspirin and Clopidogrel Resistance

View larger version (27K): [in this window] [in a new window]   Figure 2. Evidence that in vitro tests of resistance to antiplatelet drugs predict MACE. A, Aspirin resistance was determined by higher quartiles of urinary 11-dehydrothromboxane B2. P indicates trend of association. B, Clopidogrel resistance in study patients (Pts) was determined by quartiles of inhibition of ADP-induced platelet aggregation. C, Abciximab resistance was determined by VerifyNow 8 h after abciximab bolus but during infusion. Clinical follow-up was (A) 5 y, (B) 6 mo, and (C) 7 d. Reproduced with permission from Circulation.17,21,22 Copyright 2001, 2002, 2004, American Heart Association.

Thienopyridines
The thienopyridines clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Aventis) and ticlopidine (Ticlid, Bristol-Myers Squibb/Sanofi Aventis) inhibit ADP from binding to its platelet surface P2Y₁₂ receptor. Possible mechanisms of clopidogrel resistance are listed in Table 2. Matetzky et al found evidence that an in vitro test of clopidogrel resistance (ADP-induced platelet aggregation) predicts MACE, but the number of MACE was again low (Figure 2B). ²¹ The P2Y₁₂ H2 haplotype is reported to be associated with peripheral artery disease.²³

GP IIb/IIIa Antagonists
The GP IIb/IIIa antagonists abciximab (ReoPro, Eli Lilly/Centocor), eptifibatide (Integrilin, Millennium Pharmaceuticals), and tirofiban (Aggrastat, Merck) inhibit fibrinogen from binding to platelet surface GP IIb/IIIa (integrin _IIbß₃), the final common pathway of platelet aggregation. Although the term resistance has not been used in the literature with regard to GP IIb/IIIa antagonists, there is substantial patient-to-patient variability in the degree of inhibition of platelet function by GP IIb/IIIa antagonists.²² Furthermore, there is evidence that an in vitro test of abciximab resistance (VerifyNow) predicts MACE (Figure 2C). ²²

	Treatment for Resistance to Antiplatelet Agents

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
Although some clinicians change treatment on the basis of platelet function testing,²⁴ the correct treatment, if any, of aspirin resistance is unknown. Noncompliance should be considered. Increasing the dose of aspirin is unlikely to be helpful.¹⁴ Addition of a thienopyridine may be useful, with²⁵ or without continued aspirin therapy. However, increased antiplatelet therapy may increase the risk of bleeding and other side effects. Most important, no published studies address the clinical effectiveness of altering therapy on the basis of a laboratory finding of resistance to aspirin, clopidogrel, or GP IIb/IIIa antagonists. In summary, therefore, other than in research trials, it is not currently appropriate to test for resistance in patients or to change therapy on the basis of such tests.

	Acknowledgments

 
Disclosure

Dr Michelson has received grant support from Accumetrics, Bristol-Myers Squibb/Sanofi-Aventis, Centocor/Eli Lilly, and Dade Behring.

	References

Top Introduction Normal Platelet Function Platelet Function Testing in... Use of Platelet Function... Use of Platelet Function... Treatment for Resistance to... References

 
1. Michelson AD, ed. Platelets. San Diego, Calif: Academic Press; 2002.

2. Woulfe D, Yang J, Prevost N, et al. Signal transduction during the initiation, extension, and perpetuation of platelet plug formation. In: Michelson AD, ed. Platelets. San Diego, Calif: Academic Press; 2002: 197–213.

3. Ruggeri ZM. Platelets in atherothrombosis. Nature Med. 2002; 8: 1227–1234.[CrossRef][Medline] [Order article via Infotrieve]

4. Deleted in proof.

5. Michelson AD, Barnard MR, Krueger LA, et al. Flow cytometry. In: Michelson AD, ed. Platelets. San Diego, Calif: Academic Press; 2002: 297–315.

6. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide. Circulation. 1998; 98: 1721–1727.[Abstract/Free Full Text]

7. Furman MI, Benoit SE, Barnard MR, et al. Increased platelet reactivity and circulating monocyte–platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol. 1998; 31: 352–358.[Abstract/Free Full Text]

8. Michelson AD, Barnard MR, Krueger LA, et al. Circulating monocyte–platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation. 2001; 104: 1533–1537.[Abstract/Free Full Text]

9. Furman MI, Barnard MR, Krueger LA, et al. Circulating monocyte–platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol. 2001; 38: 1002–1006.[Abstract/Free Full Text]

10. Heeschen C, Dimmeler S, Hamm CW, et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med. 2003; 348: 1104–1111.[Abstract/Free Full Text]

11. Schonbeck U, Varo N, Libby P, et al. Soluble CD40L and cardiovascular risk in women. Circulation. 2001; 104: 2266–2268.[Abstract/Free Full Text]

12. Lanza GA, Sestito A, Iacovella S, et al. Relation between platelet response to exercise and coronary angiographic findings in patients with effort angina. Circulation. 2003; 107: 1378–1382.[Abstract/Free Full Text]

13. Frossard M, Fuchs I, Leitner JM, et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation. 2004; 110: 1392–1397.[Abstract/Free Full Text]

14. 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.[Abstract/Free Full Text]

15. Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res. 1993; 71: 397–403.[CrossRef][Medline] [Order article via Infotrieve]

16. Mueller MR, Salat A, Stangl P, et al. Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb Haemost. 1997; 78: 1003–1007.[Medline] [Order article via Infotrieve]

17. Eikelboom JW, Hirsh J, Weitz JI, et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002; 105: 1650–1655.[Abstract/Free Full Text]

18. Gum PA, Kottke-Marchant K, Welsh PA, et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003; 41: 961–965.[Abstract/Free Full Text]

19. Chen WH, Lee PY, Ng W, et al. 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.[Abstract/Free Full Text]

20. Grundmann K, Jaschonek K, Kleine B, et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol. 2003; 250: 63–66.[CrossRef][Medline] [Order article via Infotrieve]

21. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004; 109: 3171–3175.[Abstract/Free Full Text]

22. Steinhubl SR, Talley JD, Braden GA, et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation. 2001; 103: 2572–2578.[Abstract/Free Full Text]

23. Fontana P, Gaussem P, Aiach M, et al. P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study. Circulation. 2003; 108: 2971–2973.[Abstract/Free Full Text]

24. Pollack A. For some, aspirin may not help hearts. New York Times. July 20, 2004:F1.

25. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345: 494–502.[Abstract/Free Full Text]

Related Article:

Circulation 2004 110: 2977. [Extract] [Full Text]

This article has been cited by other articles:

				R. Paniccia, E. Antonucci, N. Maggini, E. Romano, A. M. Gori, R. Marcucci, D. Prisco, and R. Abbate Assessment of Platelet Function on Whole Blood by Multiple Electrode Aggregometry in High-Risk Patients With Coronary Artery Disease Receiving Antiplatelet Therapy Am J Clin Pathol, June 1, 2009; 131(6): 834 - 842. [Abstract] [Full Text] [PDF]

				M. J. Eisenberg, P. R. Richard, D. Libersan, and K. B. Filion Safety of Short-Term Discontinuation of Antiplatelet Therapy in Patients With Drug-Eluting Stents Circulation, March 31, 2009; 119(12): 1634 - 1642. [Abstract] [Full Text] [PDF]

				L. Ang and E. Mahmud Monitoring oral antiplatelet therapy: is it justified? Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 485 - 496. [Abstract] [PDF]

				M. Lordkipanidze, C. Pharand, T. A. Nguyen, E. Schampaert, D. A. Palisaitis, and J. G. Diodati Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients Eur. Heart J., December 1, 2008; 29(23): 2877 - 2885. [Abstract] [Full Text] [PDF]

				F. Bednar, P. Osmancik, T. Vanek, H. Mocikova, M. Jares, Z. Straka, and P. Widimsky Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET). J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 1054 - 1060. [Abstract] [Full Text] [PDF]

				P. Monagle, E. Chalmers, A. Chan, G. deVeber, F. Kirkham, P. Massicotte, and A. D. Michelson Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 887S - 968S. [Abstract] [Full Text] [PDF]

				D. Aradi, A. Konyi, L. Palinkas, T. Berki, T. Pinter, T. Tahin, I. Horvath, L. Papp, and A. Komocsi Thienopyridine Therapy Influences Late Outcome After Coronary Stent Implantation Angiology, May 1, 2008; 59(2): 172 - 178. [Abstract] [PDF]

				A. D. Michelson P2Y12 Antagonism: Promises and Challenges Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): s33 - s38. [Abstract] [Full Text] [PDF]

				C. Gachet and B. Aleil Testing antiplatelet therapy Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A28 - A34. [Abstract] [Full Text] [PDF]

				G. Davi and C. Patrono Platelet Activation and Atherothrombosis N. Engl. J. Med., December 13, 2007; 357(24): 2482 - 2494. [Full Text] [PDF]

				P. A. Gurbel, R. C. Becker, K. G. Mann, S. R. Steinhubl, and A. D. Michelson Platelet Function Monitoring in Patients With Coronary Artery Disease J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1822 - 1834. [Abstract] [Full Text] [PDF]

				E. K. Tong and S. A. Glantz Tobacco Industry Efforts Undermining Evidence Linking Secondhand Smoke With Cardiovascular Disease Circulation, October 16, 2007; 116(16): 1845 - 1854. [Abstract] [Full Text] [PDF]

				J. M. Cholette, J. S. Rubenstein, G. M. Alfieris, M. P. McDermott, W. G. Harmon, R. Vermilion, M. P. Eaton, J. J. Gangemi, and N. B. Lerner Elevated Risk of Thrombosis in Neonates Undergoing Initial Palliative Cardiac Surgery Ann. Thorac. Surg., October 1, 2007; 84(4): 1320 - 1325. [Abstract] [Full Text] [PDF]

				M. Lordkipanidze, C. Pharand, E. Schampaert, J. Turgeon, D. A. Palisaitis, and J. G. Diodati A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease Eur. Heart J., July 2, 2007; 28(14): 1702 - 1708. [Abstract] [Full Text] [PDF]

				A. D. Michelson, A. L. Frelinger, and M. I. Furman Resistance to antiplatelet drugs Eur. Heart J. Suppl., October 1, 2006; 8(suppl_G): G53 - G58. [Abstract] [Full Text] [PDF]

				D. J. Angiolillo, E. Bernardo, C. Ramirez, M. A. Costa, M. Sabate, P. Jimenez-Quevedo, R. Hernandez, R. Moreno, J. Escaned, F. Alfonso, et al. Insulin Therapy Is Associated With Platelet Dysfunction in Patients With Type 2 Diabetes Mellitus on Dual Oral Antiplatelet Treatment J. Am. Coll. Cardiol., July 18, 2006; 48(2): 298 - 304. [Abstract] [Full Text] [PDF]

				T. Wang and D. L. Bhatt Aspirin and clopidogrel resistance: an emerging clinical entity: reply Eur. Heart J., July 2, 2006; 27(14): 1754 - 1755. [Full Text] [PDF]

				A. L. Frelinger III, M. I. Furman, M. D. Linden, Y. Li, M. L. Fox, M. R. Barnard, and A. D. Michelson Residual Arachidonic Acid-Induced Platelet Activation via an Adenosine Diphosphate-Dependent but Cyclooxygenase-1- and Cyclooxygenase-2-Independent Pathway: A 700-Patient Study of Aspirin Resistance Circulation, June 27, 2006; 113(25): 2888 - 2896. [Abstract] [Full Text] [PDF]

				E. D. Michos, R. Ardehali, R. S. Blumenthal, R. A. Lange, and H. Ardehali Aspirin and Clopidogrel Resistance Mayo Clin. Proc., April 1, 2006; 81(4): 518 - 526. [Abstract] [Full Text] [PDF]

				D. M. Becker, J. Segal, D. Vaidya, L. R. Yanek, J. E. Herrera-Galeano, P. F. Bray, T. F. Moy, L. C. Becker, and N. Faraday Sex Differences in Platelet Reactivity and Response to Low-Dose Aspirin Therapy JAMA, March 22, 2006; 295(12): 1420 - 1427. [Abstract] [Full Text] [PDF]

				T. H. Wang, D. L. Bhatt, and E. J. Topol Aspirin and clopidogrel resistance: an emerging clinical entity Eur. Heart J., March 2, 2006; 27(6): 647 - 654. [Abstract] [Full Text] [PDF]

				D. Paparella, A. Galeone, M. T. Venneri, M. Coviello, G. Scrascia, N. Marraudino, M. Quaranta, L. de Luca Tupputi Schinosa, and S. J. Brister Activation of the coagulation system during coronary artery bypass grafting: Comparison between on-pump and off-pump techniques J. Thorac. Cardiovasc. Surg., February 1, 2006; 131(2): 290 - 297. [Abstract] [Full Text] [PDF]

				A. O. Maree, R. J. Curtin, M. Dooley, R. M. Conroy, P. Crean, D. Cox, and D. J. Fitzgerald Platelet Response to Low-Dose Enteric-Coated Aspirin in Patients With Stable Cardiovascular Disease J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1258 - 1263. [Abstract] [Full Text] [PDF]

				A. L. Frelinger III and A. D. Michelson Clopidogrel: Linking Evaluation of Platelet Response Variability to Mechanism of Action J. Am. Coll. Cardiol., August 16, 2005; 46(4): 646 - 647. [Full Text] [PDF]

				T. A. Nguyen, J. G. Diodati, and C. Pharand Resistance to clopidogrel: A review of the evidence J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1157 - 1164. [Abstract] [Full Text] [PDF]

				A. A. Hassan and M. H. Kroll Acquired Disorders of Platelet Function Hematology, January 1, 2005; 2005(1): 403 - 408. [Abstract] [Full Text] [PDF]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Michelson, A. D. Search for Related Content PubMed PubMed Citation Articles by Michelson, A. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID Related Collections Arterial thrombosis Platelet function inhibitors Thrombosis risk factors Other Treatment Other diagnostic testing Antiplatelets Platelets Related Article