VIEWPOINT
Platelet Function Monitoring in Patients With Coronary Artery Disease
Paul A. Gurbel, MD*,
Richard C. Becker, MD ,*,
Kenneth G. Mann, PhD ,
Steven R. Steinhubl, MD and
Alan D. Michelson, MD||
* Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland
Cardiovascular Thrombosis Center, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
University of Vermont, Burlington, Vermont
Division of Cardiology, University of Kentucky, Lexington, Kentucky
|| Center for Platelet Function Studies, Departments of Pediatrics, Medicine, and Pathology, University of Massachusetts Medical School, Worcester, Massachusetts.
Manuscript received January 3, 2007;
revised manuscript received July 24, 2007,
accepted July 31, 2007.
* Reprint requests and correspondence: Dr. Richard C. Becker, Duke Clinical Research Institute, 2400 Pratt Street, Terrace Level, Room 0311, Durham, North Carolina 27705. (Email: richard.becker{at}duke.edu).
Studies focused on patient responsiveness to antiplatelet therapies, particularly aspirin and clopidogrel, have increased in recent years. However, the relations of in vivo platelet function and adverse clinical events to results of ex vivo platelet function tests remain largely unknown. This article describes current methods of measuring platelet function in various clinical and research situations and their advantages and disadvantages, reviews evidence for antiplatelet response variability and resistance, discusses the potential pitfalls of monitoring platelet function, and demonstrates emerging data supporting the positive clinical and treatment implications of platelet function testing.
|
Abbreviations and Acronyms
| | ACS = acute coronary syndromes | | CAD = coronary artery disease | | COX = cyclooxygenase | | GP = glycoprotein | | INR = international normalized ratio | | LTA = light transmittance aggregometry | | MACE = major adverse cardiac events | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | VASP = vasodilator-stimulated phosphoprotein |
|
This article has been cited by other articles:

|
 |

|
 |
 
P. MacMULLAN
Guilty by Association: Platelet Reactivity and Inflammation in Psoriatic Arthritis
J Rheumatol,
February 1, 2012;
39(2):
210 - 211.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Gurbel, E. M. Ohman, Y.-H. Jeong, and U. S. Tantry
Toward a therapeutic window for antiplatelet therapy in the elderly
Eur. Heart J.,
January 22, 2012;
(2012)
ehr458v1.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. M. Hall, S. Banerjee, and D. K. McGuire
Variability of clopidogrel response in patients with type 2 diabetes mellitus
Diabetes and Vascular Disease Research,
October 1, 2011;
8(4):
245 - 253.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Parodi, R. Marcucci, R. Valenti, A. M. Gori, A. Migliorini, B. Giusti, P. Buonamici, G. F. Gensini, R. Abbate, and D. Antoniucci
High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI
JAMA,
September 21, 2011;
306(11):
1215 - 1223.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Lanza, G. Scalone, L. Barone, F. Infusino, I. Coviello, A. Di Monaco, A. Delogu, I. Battipaglia, A. De Nisco, A. Sestito, et al.
Platelet reactivity and endothelial function in children of patients with early acute myocardial infarction
Eur. Heart J.,
August 2, 2011;
32(16):
2042 - 2049.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. C. Becker, B. Jacobson, S. Singh, K. Sliwa, S. Stewart, E. Libhaber, and M. R. Essop
The Thrombotic Profile of Treatment-Naive HIV-Positive Black South Africans With Acute Coronary Syndromes
Clinical and Applied Thrombosis/Hemostasis,
June 1, 2011;
17(3):
264 - 272.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Sagdilek, A. Korkmaz, S. Oter, F. Avcu, T. Topal, M. Ozler, B. Uysal, O. Nevruz, C. Beyan, and K. Ozluk
The Similarity Between Aspirin Treatment and the Lack of Response to Epinephrine and the Frequency of Aspirin Resistance in Healthy Males
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2011;
17(2):
202 - 207.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Kimmelstiel, P. Zhang, N. K. Kapur, A. Weintraub, B. Krishnamurthy, V. Castaneda, L. Covic, and A. Kuliopulos
Bivalirudin Is a Dual Inhibitor of Thrombin and Collagen-Dependent Platelet Activation in Patients Undergoing Percutaneous Coronary Intervention
Circ Cardiovasc Interv,
April 1, 2011;
4(2):
171 - 179.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Gurbel and U. S. Tantry
An Initial Experiment With Personalized Antiplatelet Therapy: The GRAVITAS Trial
JAMA,
March 16, 2011;
305(11):
1136 - 1137.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Ambrosio, S. Steinhubl, P. Gresele, I. Tritto, C. Zuchi, M. E. Bertrand, A. M. Lincoff, J. W. Moses, E. M. Ohman, H. D. White, et al.
Impact of chronic antiplatelet therapy before hospitalization on ischemic and bleeding events in invasively managed patients with acute coronary syndromes: the ACUITY trial
European Journal of Cardiovascular Prevention & Rehabilitation,
February 1, 2011;
18(1):
121 - 128.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Antoniucci
No Role for Triple Antiplatelet Therapy?
J. Am. Coll. Cardiol.,
January 18, 2011;
57(3):
290 - 291.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Bonello, S. Armero, O. Ait Mokhtar, J. Mancini, P. Aldebert, N. Saut, N. Bonello, P. Barragan, S. Arques, M.-P. Giacomoni, et al.
Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19*2 Loss of Function Polymorphism
J. Am. Coll. Cardiol.,
November 9, 2010;
56(20):
1630 - 1636.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. J. Smit, J. W. van Werkum, J. ten Berg, R. Slingerland, J. P. Ottervanger, T. Heestermans, T. Dill, C. Hamm, A. W. J. van 't Hof, and on behalf of the Ongoing Tirofiban in Myocardial I
Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy
Heart,
November 1, 2010;
96(22):
1815 - 1820.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. L. Mega, T. Simon, J.-P. Collet, J. L. Anderson, E. M. Antman, K. Bliden, C. P. Cannon, N. Danchin, B. Giusti, P. Gurbel, et al.
Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-analysis
JAMA,
October 27, 2010;
304(16):
1821 - 1830.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Gurbel and U. S. Tantry
Acceptance of High Platelet Reactivity as a Risk Factor: Now, What Do We Do About It?
J. Am. Coll. Cardiol. Intv.,
October 1, 2010;
3(10):
1008 - 1010.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Bonello, U. S. Tantry, R. Marcucci, R. Blindt, D. J. Angiolillo, R. Becker, D. L. Bhatt, M. Cattaneo, J. P. Collet, T. Cuisset, et al.
Consensus and Future Directions on the Definition of High On-Treatment Platelet Reactivity to Adenosine Diphosphate
J. Am. Coll. Cardiol.,
September 14, 2010;
56(12):
919 - 933.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Mahla, H. Metzler, U. S. Tantry, and P. A. Gurbel
Controversies in Oral Antiplatelet Therapy in Patients Undergoing Aortocoronary Bypass Surgery
Ann. Thorac. Surg.,
September 1, 2010;
90(3):
1040 - 1051.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. M. Roden and A. R. Shuldiner
Responding to the Clopidogrel Warning by the US Food and Drug Administration: Real Life Is Complicated
Circulation,
August 3, 2010;
122(5):
445 - 448.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Kalyanasundaram, P. B. Berger, and M. J. Price
Routine Platelet Testing Should Not Be Performed on All Patients Undergoing Percutaneous Coronary Intervention
Circ Cardiovasc Interv,
June 1, 2010;
3(3):
284 - 288.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Testa, R. Bhindi, W. J. Van Gaal, R. A. Latini, S. Pizzocri, S. Lanotte, G. G. L. Biondi Zoccai, M. Valgimigli, M. L. Laudisa, N. Brambilla, et al.
What is the risk of intensifying platelet inhibition beyond clopidogrel? A systematic review and a critical appraisal of the role of prasugrel
QJM,
June 1, 2010;
103(6):
367 - 377.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. P. Alexander and E. D. Peterson
Minimizing the Risks of Anticoagulants and Platelet Inhibitors
Circulation,
May 4, 2010;
121(17):
1960 - 1970.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sibbing, W. Koch, D. Gebhard, T. Schuster, S. Braun, J. Stegherr, T. Morath, A. Schomig, N. von Beckerath, and A. Kastrati
Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement
Circulation,
February 2, 2010;
121(4):
512 - 518.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Mac Mullan, A. J. Peace, A. M. Madigan, A. F. Tedesco, D. Kenny, and G. M. McCarthy
Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target
Rheumatology,
February 1, 2010;
49(2):
240 - 245.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. C. Becker, J. Scheiman, H. L. Dauerman, F. Spencer, S. Rao, M. Sabatine, D. A. Johnson, F. Chan, N. S. Abraham, E. M.M. Quigley, et al.
Management of Platelet-Directed Pharmacotherapy in Patients With Atherosclerotic Coronary Artery Disease Undergoing Elective Endoscopic Gastrointestinal Procedures
J. Am. Coll. Cardiol.,
December 8, 2009;
54(24):
2261 - 2276.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Fauler
Clinical pharmacology of antithrombotic drugs in coronary artery disease
Therapeutic Advances in Cardiovascular Disease,
December 1, 2009;
3(6):
465 - 478.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Migliorini, R. Valenti, R. Marcucci, G. Parodi, G. Giuliani, P. Buonamici, G. Cerisano, N. Carrabba, G. F. Gensini, R. Abbate, et al.
High Residual Platelet Reactivity After Clopidogrel Loading and Long-Term Clinical Outcome After Drug-Eluting Stenting for Unprotected Left Main Coronary Disease
Circulation,
December 1, 2009;
120(22):
2214 - 2221.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Gurbel, U. S. Tantry, and A. R. Shuldiner
The Worry About Clopidogrel "Nonresponsiveness": Identification and Treatment in the Post-Percutaneous Coronary Intervention Patient
J. Am. Coll. Cardiol. Intv.,
November 1, 2009;
2(11):
1102 - 1104.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. Roldan, and D. J. Angiolillo
Pharmacogenetics in Cardiovascular Antithrombotic Therapy
J. Am. Coll. Cardiol.,
September 15, 2009;
54(12):
1041 - 1057.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Shimbo, W. Chaplin, S. Kuruvilla, L. T. Wasson, D. Abraham, and M. M. Burg
Hostility and Platelet Reactivity in Individuals Without a History of Cardiovascular Disease Events
Psychosom Med,
September 1, 2009;
71(7):
741 - 747.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A R Muir, M F McMullin, C Patterson, and P P McKeown
Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease
Heart,
August 1, 2009;
95(15):
1225 - 1229.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Hjemdahl
Aspirin resistance testing not ready for "prime time"
Heart,
August 1, 2009;
95(15):
1220 - 1222.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Valgimigli, G. Campo, N. de Cesare, E. Meliga, P. Vranckx, A. Furgieri, D. J. Angiolillo, M. Sabate, M. Hamon, A. Repetto, et al.
Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study
Circulation,
June 30, 2009;
119(25):
3215 - 3222.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Maugeri, P. Rovere-Querini, V. Evangelista, C. Covino, A. Capobianco, M. T. S. Bertilaccio, A. Piccoli, L. Totani, D. Cianflone, A. Maseri, et al.
Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program
Blood,
May 21, 2009;
113(21):
5254 - 5265.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. Wesley, F. X. McGowan, R. A. Castro, S. Dissanayake, D. Zurakowski, and J. A. DiNardo
The Effect of Milrinone on Platelet Activation as Determined by TEG(R) Platelet MappingTM
Anesth. Analg.,
May 1, 2009;
108(5):
1425 - 1429.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Tanaka, N. S. Key, and J. H. Levy
Blood Coagulation: Hemostasis and Thrombin Regulation
Anesth. Analg.,
May 1, 2009;
108(5):
1433 - 1446.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y.-H. Jeong, S.-W. Lee, B.-R. Choi, I.-S. Kim, M.-K. Seo, C. H. Kwak, J.-Y. Hwang, and S.-W. Park
Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity: Results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) Randomized Study
J. Am. Coll. Cardiol.,
March 31, 2009;
53(13):
1101 - 1109.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sibbing, S. Braun, T. Morath, J. Mehilli, W. Vogt, A. Schomig, A. Kastrati, and N. von Beckerath
Platelet Reactivity After Clopidogrel Treatment Assessed With Point-of-Care Analysis and Early Drug-Eluting Stent Thrombosis
J. Am. Coll. Cardiol.,
March 10, 2009;
53(10):
849 - 856.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Mahla, M. J. Antonino, U. S. Tantry, and P. A. Gurbel
Point-of-Care Platelet Function Analysis: Ready for Prime Time?
J. Am. Coll. Cardiol.,
March 10, 2009;
53(10):
857 - 859.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Gurbel, K. P. Bliden, J. F. Saucedo, T. A. Suarez, J. DiChiara, M. J. Antonino, E. Mahla, A. Singla, W. R. Herzog, A. K. Bassi, et al.
Bivalirudin and Clopidogrel With and Without Eptifibatide for Elective Stenting: Effects on Platelet Function, Thrombelastographic Indexes, and Their Relation to Periprocedural Infarction: Results of the CLEAR PLATELETS-2 (Clopidogrel With Eptifibatide to Arrest the Reactivity of Platelets) Study
J. Am. Coll. Cardiol.,
February 24, 2009;
53(8):
648 - 657.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Marcucci, A. M. Gori, R. Paniccia, B. Giusti, S. Valente, C. Giglioli, P. Buonamici, D. Antoniucci, R. Abbate, and G. F. Gensini
Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay: A 12-Month Follow-Up
Circulation,
January 20, 2009;
119(2):
237 - 242.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Cairns and J. Eikelboom
The Pursuit of Clinically Relevant Measures of Platelet Function After Antiplatelet Drug Therapy
J. Am. Coll. Cardiol.,
December 9, 2008;
52(24):
1978 - 1980.
[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. Y. Chan, F. Andreotti, and R. C. Becker
Hypercoagulable States in Cardiovascular Disease
Circulation,
November 25, 2008;
118(22):
2286 - 2297.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Siller-Matula, I. Lang, G. Christ, and B. Jilma
Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel
J. Am. Coll. Cardiol.,
November 4, 2008;
52(19):
1557 - 1563.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Gori, R. Marcucci, A. Migliorini, R. Valenti, G. Moschi, R. Paniccia, P. Buonamici, G. F. Gensini, R. Vergara, R. Abbate, et al.
Incidence and Clinical Impact of Dual Nonresponsiveness to Aspirin and Clopidogrel in Patients With Drug-Eluting Stents
J. Am. Coll. Cardiol.,
August 26, 2008;
52(9):
734 - 739.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. P. Bliden, J. DiChiara, L. Lawal, A. Singla, M. J. Antonino, B. A. Baker, W. L. Bailey, U. S. Tantry, and P. A. Gurbel
The Association of Cigarette Smoking With Enhanced Platelet Inhibition by Clopidogrel
J. Am. Coll. Cardiol.,
August 12, 2008;
52(7):
531 - 533.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Li, E. Yow, K. Y. Berezny, P. M. Bokesch, M. Takahashi, T. P. Graham Jr, S. P. Sanders, D. Sidi, D. Bonnet, P. Ewert, et al.
Response to Letter Regarding Article, "Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children: Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial"
Circulation,
August 12, 2008;
118(7):
e121 - e121.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. R. Holmes Jr and D. O. Williams
Catheter-Based Treatment of Coronary Artery Disease: Past, Present, and Future
Circ Cardiovasc Interv,
August 1, 2008;
1(1):
60 - 73.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sibbing, G. Busch, S. Braun, S. Jawansky, A. Schomig, A. Kastrati, I. Ott, and N. von Beckerath
Impact of bivalirudin or unfractionated heparin on platelet aggregation in patients pretreated with 600 mg clopidogrel undergoing elective percutaneous coronary intervention
Eur. Heart J.,
June 2, 2008;
29(12):
1504 - 1509.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Cairns and J. Eikelboom
Clopidogrel Resistance: More Grist for the Mill
J. Am. Coll. Cardiol.,
May 20, 2008;
51(20):
1935 - 1937.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Touat, L. Lepage, V. Ollivier, P. Nataf, U. Hvass, J. Labreuche, M. Jandrot-Perrus, J.-B. Michel, and G. Jondeau
Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm
Arterioscler Thromb Vasc Biol,
May 1, 2008;
28(5):
940 - 946.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. J. Kereiakes and P. A. Gurbel
Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention
J. Am. Coll. Cardiol. Intv.,
April 1, 2008;
1(2):
111 - 121.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|