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Khan H, Jain S, Gallant RC, Syed MH, Zamzam A, Al-Omran M, Rand ML, Ni H, Abdin R, Qadura M. Plateletworks ® as a Point-of-Care Test for ASA Non-Sensitivity. J Pers Med 2021; 11:813. [PMID: 34442457 PMCID: PMC8398990 DOI: 10.3390/jpm11080813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/17/2021] [Accepted: 08/18/2021] [Indexed: 12/18/2022] Open
Abstract
Aspirin (ASA) therapy is proven to be effective in preventing adverse cardiovascular events; however, up to 30% of patients are non-sensitive to their prescribed ASA dosage. In this pilot study, we demonstrated, for the first time, how ASA non-sensitivity can be diagnosed using Plateletworks®, a point-of-care platelet function test. Patients prescribed 81 mg of ASA were recruited in a series of two successive phases-a discovery phase and a validation phase. In the discovery phase, a total of 60 patients were recruited to establish a cut-off point (COP) for ASA non-sensitivity using Plateletworks®. Each sample was simultaneously cross-referenced with a light transmission aggregometer (LTA). Our findings demonstrated that >52% maximal platelet aggregation using Plateletworks® had a sensitivity, specificity, and likelihood ratio of 80%, 70%, and 2.67, respectively, in predicting ASA non-sensitivity. This COP was validated in a secondary cohort of 40 patients prescribed 81 mg of ASA using Plateletworks® and LTA. Our data demonstrated that our established COP had a 91% sensitivity and 69% specificity in identifying ASA non-sensitivity using Plateletworks®. In summary, Plateletworks® is a point-of-care platelet function test that can appropriately diagnose ASA non-sensitive patients with a sensitivity exceeding 80%.
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Affiliation(s)
- Hamzah Khan
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
| | - Shubha Jain
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
| | - Reid C. Gallant
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (R.C.G.); (H.N.)
| | - Muzammil H. Syed
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
| | - Abdelrahman Zamzam
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
| | - Mohammed Al-Omran
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (R.C.G.); (H.N.)
- Department of Surgery, University of Toronto, Toronto, ON M4B 1B3, Canada
| | - Margaret L. Rand
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M4B 1B3, Canada;
- Departments of Biochemistry and Pediatrics, University of Toronto, Toronto, ON M4B 1B3, Canada
- Translational Medicine, Research Institute, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON M4B 1B3, Canada
| | - Heyu Ni
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (R.C.G.); (H.N.)
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M4B 1B3, Canada;
| | - Rawand Abdin
- Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada;
| | - Mohammad Qadura
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (H.K.); (S.J.); (M.H.S.); (A.Z.); (M.A.-O.)
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M4B 1B3, Canada; (R.C.G.); (H.N.)
- Department of Surgery, University of Toronto, Toronto, ON M4B 1B3, Canada
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Dovlatova N, Heptinstall S. Platelet aggregation measured by single-platelet counting and using PFA-100 devices. Platelets 2018; 29:656-661. [PMID: 29985716 DOI: 10.1080/09537104.2018.1492109] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Platelets play a crucial role in haemostasis and thrombosis and evaluation of platelet function in vitro, in particular platelet aggregation responses, has been one of the most common and useful ways of evaluating the risk of bleeding and thrombotic events and assessing the effects of various compounds and conditions on platelets. Traditional approaches to assessing platelet aggregation require specialised equipment and trained laboratory personnel and have other limitations. Studying platelet aggregation in whole blood offers a more physiologically relevant measurement. Additionally, certain approaches could be more widely available than in specialised laboratories. Here we summarise the application of the platelet function analyser (PFA-100), an accessible first point-of-care test for platelet function in whole blood, and the less established, but promising approach of assessing platelet aggregation by single-platelet counting that can also be performed in whole blood. The possibilities of a wider and more accessible application of the latter methodology are also discussed.
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Affiliation(s)
- Natalia Dovlatova
- a Thrombosis and Haemostasis Research Group, Division of Clinical Neuroscience , University of Nottingham , Nottingham, United Kingdom.,b Platelet Solutions Ltd ., Nottingham , United Kingdom
| | - Stan Heptinstall
- a Thrombosis and Haemostasis Research Group, Division of Clinical Neuroscience , University of Nottingham , Nottingham, United Kingdom.,b Platelet Solutions Ltd ., Nottingham , United Kingdom
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3
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Abstract
In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.
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Affiliation(s)
- Rita Paniccia
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Raffaella Priora
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | | | - Rosanna Abbate
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
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4
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Paniccia R, Priora R, Liotta AA, Maggini N, Abbate R. Assessment of platelet function: Laboratory and point-of-care methods. World J Transl Med 2014; 3:69-83. [DOI: 10.5528/wjtm.v3.i2.69] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 03/14/2014] [Accepted: 04/29/2014] [Indexed: 02/05/2023] Open
Abstract
In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. “Old” platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis in platelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.
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5
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Orlov D, McCluskey SA, Selby R, Yip P, Pendergrast J, Karkouti K. Platelet Dysfunction as Measured by a Point-of-Care Monitor is an Independent Predictor of High Blood Loss in Cardiac Surgery. Anesth Analg 2014; 118:257-263. [DOI: 10.1213/ane.0000000000000054] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
Platelet function tests have been traditionally used to aid in the diagnosis and management of patients with bleeding problems. Given the role of platelets in atherothrombosis, several dedicated platelet function instruments are now available that are simple to use and can be used as point-of-care assays. These can provide rapid assessment of platelet function within whole blood without the requirement of sample processing. Some tests can be used to monitor antiplatelet therapy and assess risk of bleeding and thrombosis, although current guidelines advise against this. This article discusses the potential utility of tests/instruments that are available.
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Affiliation(s)
- Paul Harrison
- School of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK.
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7
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Jennings LK, Kotha J. The Utility of Platelet and Coagulation Testing of Antithrombotics: Fusing Science with Patient Care. Drug Dev Res 2013; 74:587-593. [PMID: 24489427 PMCID: PMC3902984 DOI: 10.1002/ddr.21119] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Indexed: 01/09/2023]
Abstract
[Table: see text] There is an increasing need for the standardization of platelet function and coagulation testing for the assessment of antithrombotic therapies. Investigators continue to strive to identify ideal laboratory testing and monitoring procedures for acquired and inherited platelet function defects as well as for evaluating patient status when treated with existing or emerging antithrombotics. These therapies are used primarily in the treatment of ischemic complications. In patients receiving antithrombotic therapy, the balance between hemostasis and thrombosis is a challenge as there is an ongoing risk for bleeding when patients are receiving antiplatelet agents or anticoagulants to lessen their risk for secondary thrombotic events. There are several diverse tests for monitoring anticoagulant therapy; however, as new agents are developed, more specific tests will be required to directly assess these agents in relationship to overall coagulation status. Research in the platelet biology field is ongoing to provide point-of-care methodologies for the assessment of platelet reactivity in terms of both bleeding and thrombosis risk. Currently there are no instruments that reliably assess the risk of bleeding. The challenges that routinely faced are the complexity of physiology, the need for standardization of platelet testing methodology, and the necessity for appropriate interpretation of the test results.
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Affiliation(s)
- Lisa K Jennings
- The University of Tennessee Health Science Center and CirQuest Labs Memphis, TN, USA
| | - Jayaprakash Kotha
- The University of Tennessee Health Science Center and CirQuest Labs Memphis, TN, USA
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8
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9
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10
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Ainiding G, Yamashita KI, Torii T, Furuta K, Isobe N, Matsushita T, Masaki K, Matsumoto S, Kira JI. Clinical disability progression and platelet GP IIb/IIIa values in patients with atopic myelitis. J Neuroimmunol 2012; 246:108-12. [PMID: 22484027 DOI: 10.1016/j.jneuroim.2012.03.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 02/27/2012] [Accepted: 03/14/2012] [Indexed: 11/30/2022]
Abstract
We aimed to clarify the disability progression and platelet aggregative function in atopic myelitis (AM). Seventeen AM patients and 35 healthy controls were subjected to clinico-allergological evaluations and glycoprotein IIb/IIIa (GP IIb/IIIa) measurements using a VerifyNow assay system. In AM patients, the disease duration had significant positive correlations with the Kurtzke Expanded Disability Status Scale scores and Sensory Functional Scale scores. The GP IIb/IIIa values were significantly higher in AM patients than in controls as well as in females compared with males. AM is essentially a progressive disease affecting the sensory system, and involves an increased platelet aggregative function.
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Affiliation(s)
- Gulibahaer Ainiding
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Currently available methods for platelet function analysis: advantages and disadvantages. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2011; 12:312-22. [DOI: 10.1016/j.carrev.2010.09.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Accepted: 09/02/2010] [Indexed: 11/23/2022]
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12
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Point-of-care platelet function testing in patients undergoing PCI: between a rock and a hard place. Neth Heart J 2011; 15:299-305. [PMID: 18030318 DOI: 10.1007/bf03086004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Since recent studies have linked an impaired response to antiplatelet therapy with a higher incidence of atherothrombotic events, the monitoring of the efficacy of antiplatelet therapy in the individual patient has attracted much attention. In the present report, we demonstrate that platelet function testing with several point-of-care assays results in ambiguous and conflicting results: some assays indicated that the patient's platelets were insufficiently inhibited by clopidogrel whereas other assays reported an adequate response. Therefore, platelet function assays should not be used solely to guide treatment decisions, and tailor-made antithrombotic treatment has to wait for the most predictive platelet function test to emerge for measuring the risk for thrombotic complications after stenting. Until then, daily clinical practice should not be guided by point-of-care platelet function testing. (Neth Heart J 2007;15:299-305.).
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13
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Sobieraj-Teague M, Eikelboom JW. Point-of-care testing for assessment of adequacy of oral antiplatelet therapy in patients with cardiovascular disease. Future Cardiol 2010; 6:289-99. [PMID: 20462336 DOI: 10.2217/fca.10.20] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Studies with recently introduced point-of-care (POC) platelet function tests have shown that individuals are variably responsive to aspirin and clopidogrel therapy, and that hyporesponsiveness to antiplatelet therapy is associated with an increased risk of cardiovascular events. However, the currently available POC tests have undergone only limited clinical evaluation and clinicians are uncertain about the best POC test, the optimal cut-off point to define hyporesponsiveness in different patient populations and clinical settings, the appropriate management of patients demonstrating hyporesponsiveness and the cost effectiveness of adjusting treatment on the basis of the results of POC platelet function testing. Several large randomized controlled trials currently underway are examining whether adjusting antiplatelet therapy on the basis of a POC test result can improve patient-important outcomes. Until these issues are resolved, POC testing to monitor antiplatelet therapy will largely remain a research tool and patients should continue to receive oral antiplatelet therapy without routine monitoring at doses that have been demonstrated to be effective in randomized controlled trials.
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Deibele AJ, Jennings LK, Tcheng JE, Neva C, Earhart AD, Gibson CM. Intracoronary Eptifibatide Bolus Administration During Percutaneous Coronary Revascularization for Acute Coronary Syndromes With Evaluation of Platelet Glycoprotein IIb/IIIa Receptor Occupancy and Platelet Function. Circulation 2010; 121:784-91. [DOI: 10.1161/circulationaha.109.882746] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background—
Eptifibatide reduces major adverse cardiac events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Intracoronary bolus administration of eptifibatide may result in higher levels of platelet glycoprotein IIb/IIIa receptor occupancy in the local coronary bed, disaggregate thrombus in the epicardial artery and microvasculature, and thereby improve coronary flow.
Methods and Results—
Patients undergoing PCI for an acute coronary syndrome were randomized to either intracoronary or intravenous bolus administration of eptifibatide. The primary end point was the local glycoprotein IIb/IIIa receptor occupancy measured in the coronary sinus. There were no angiographic, electrophysiological, or other adverse findings attributable to intracoronary eptifibatide. Platelet glycoprotein IIb/IIIa receptor occupancy was significantly greater with intracoronary versus intravenous administration: first bolus, 94±9% versus 51±15% (
P
<0.001); and second bolus, 99±2% versus 91±4% (
P
=0.001), respectively. Microvascular perfusion was significantly improved as measured by the corrected thrombolysis in myocardial infarction frame count (cTFC) with intracoronary versus intravenous administration: pre-PCI, 36 (median) (25th and 75th percentiles, 16 and 64) versus 31 (25th and 75th percentiles, 23 and 45;
P
=0.8); and post-PCI, 18 (25th and 75th percentiles, 10 and 22) versus 25 (25th and 75th percentiles, 22 and 35;
P
=0.007), respectively. The only multivariate predictor associated with a post-PCI cTFC rank score was the first bolus glycoprotein IIb/IIIa receptor occupancy (
P
<0.001).
Conclusions—
Intracoronary bolus administration of eptifibatide during PCI in patients with acute coronary syndromes results in higher local platelet glycoprotein IIb/IIIa receptor occupancy, which is associated with improved microvascular perfusion demonstrated by an improved cTFC.
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Affiliation(s)
- Albert J. Deibele
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
| | - Lisa K. Jennings
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
| | - James E. Tcheng
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
| | - Cathy Neva
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
| | - Angela D. Earhart
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
| | - C. Michael Gibson
- From the Duluth Clinic, Division of Cardiology, Duluth, Minn (A.J.D., C.N.); University of Tennessee, Vascular Biology Center of Excellence, Memphis (L.K.J., A.D.E.); Duke University Medical Center, Division of Cardiology, Durham, NC (J.E.T.); and Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, Mass (C.M.G.)
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15
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Gibbs NM. Point-of-care assessment of antiplatelet agents in the perioperative period: a review. Anaesth Intensive Care 2009; 37:354-69. [PMID: 19499855 DOI: 10.1177/0310057x0903700317] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The aim of this paper was to review the strengths and limitations of current 'point-of-care' techniques for the detection of antiplatelet drug effects. The review was based on a Medline search for articles with key words related to "platelet function tests", "point-of-care", and "anaesthesia", published in English between January 1996 and September 2008. It was found that global assessments of 'haemostasis', such as the standard thrombelastograph, Sonoclot, Clot Signature Analyser and Hemodyne, are not specific for platelet function and are essentially insensitive to cyclooxygenase inhibitors (aspirin, non-steroidal anti-inflammatory drugs) and P2Y12 antagonists (ticlopidine, clopidogrel). Global assessments of 'platelet function', such as the PFA-100 and PlateletWorks, are more specific for platelet function, but also have limited sensitivity for cyclooxygenase inhibitors and P2Y12 antagonists. The newer devices developed specifically for the assessment of antiplatelet drugs, such as Platelet Mapping, the Impact Cone and Platelet Analyser and the VerifyNow, are more promising, but are not as sensitive as laboratory platelet aggregometry. All three categories of devices detect G(p)II(b)/III(a) antagonists (abciximab, tirofiban, eptifibatide) activity, but not all provide quantitative assessments for monitoring therapy. The limitations appeared to be related to the complexity of platelet function, the multiple pathways of platelet activation, the wide interpatient variability in platelet responses and the interdependence between platelets and other aspects of coagulation. The strengths and limitations of point-of-care devices should be appreciated before they are used to assist clinical decision-making in the perioperative period.
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Affiliation(s)
- N M Gibbs
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
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Speich HE, Earhart AD, Hill SN, Cholera S, Kueter TJ, Smith JN, White MM, Jennings LK. Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab. J Thromb Haemost 2009; 7:983-91. [PMID: 19548907 DOI: 10.1111/j.1538-7836.2009.03432.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Utilization of glycoprotein IIb-IIIa (GPIIb-IIIa) inhibitors improves outcomes of patients with acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention (PCI). These results may be related to the ability of the inhibitors to destabilize coronary thrombi, reduce microembolization, and restore vessel patency. OBJECTIVE To evaluate in vitro the ability of GPIIb-IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus. METHODS Antagonist-induced disaggregation was assayed in plasma by aggregometry, as well as in whole blood by point of care and capillary perfusion systems. Fibrinogen dissociation from the platelet surface was quantified by flow cytometry. RESULTS Significant disaggregation of 5 microm ADP-induced aggregates was observed after addition of either agent. The maximum extent and rate of disaggregation were significantly higher with eptifibatide than with abciximab. Both antagonists also dispersed 2 microg mL(-1) collagen-induced aggregates, again with eptifibatide having a greater effect. Eptifibatide, but not abciximab (up to 10 microg mL(-1)), was efficient at dissociating aggregates to single platelets in whole blood and dispersing aggregates that had been aged for 30 min before treatment. Eptifibatide also reduced existing thrombus burden in the perfusion model under arterial flow conditions. A key mechanism of aggregate dispersal was antagonist-induced displacement of platelet-bound fibrinogen, which was greater with eptifibatide, a competitive inhibitor of fibrinogen binding, than with the noncompetitive inhibitor, abciximab. CONCLUSIONS These results suggest that drug concentration and residence time, along with thrombus extent and age, may be critical determinants in promoting timely recanalization.
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Affiliation(s)
- H E Speich
- Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
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17
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Lippi G, Favaloro EJ, Salvagno GL, Franchini M. Laboratory assessment and perioperative management of patients on antiplatelet therapy: from the bench to the bedside. Clin Chim Acta 2009; 405:8-16. [PMID: 19351529 DOI: 10.1016/j.cca.2009.03.055] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2009] [Revised: 03/25/2009] [Accepted: 03/29/2009] [Indexed: 01/29/2023]
Abstract
The contribution of platelets in the pathophysiology of thromboses has established antiplatelet therapy as a cornerstone for prevention or treatment of these disorders. However, patients on antiplatelet drugs undergoing surgery face the life-threatening dilemma between the risk of perioperative thrombosis by ceasing therapy and restoring platelet function versus the risk of surgical bleeding by its continuation. According to their mechanism of action, antiplatelet drugs can be conventionally classified as agents that inhibit cyclooxygenase, block the platelet adenosine diphosphate P2Y12 receptor, inhibit phosphodiesterase, or block platelet glycoprotein IIb/IIIa. Although several tests have been developed to assess platelet inhibition by most of these compounds, studies to date have not been able to reliably evaluate the diagnostic efficiency of these tests to predict hemorrhage and/or blood loss, and accordingly perioperative assessment of drug-induced platelet inhibition cannot be recommended as yet. Although several management options are available to counteract the hemorrhagic risk of surgical patients using antiplatelet agents, perioperative discontinuation of these drugs is the preferable choice wherever possible. The use of platelet transfusions should be limited where necessary to the treatment of major, life-threatening bleeding. The contribution of newer hemostatic agents, such as desmopressin and recombinant activated factor VII, is yet to be fully determined, and there remain many challenges and unresolved issues in the clinical care of these patients.
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Affiliation(s)
- Giuseppe Lippi
- Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Italy.
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18
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van Werkum JW, Hackeng CM, Smit JJJ, van’t Hof AWJ, Verheugt FWA, ten Berg JM. Monitoring antiplatelet therapy with point-of-care platelet function assays: a review of the evidence. Future Cardiol 2008; 4:33-55. [DOI: 10.2217/14796678.4.1.33] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Multiple studies have demonstrated that subgroups of patients receiving combination therapy with aspirin and clopidogrel fail to produce the anticipated antiplatelet effect, and various terms such as ‘aspirin resistance’, ‘clopidogrel resistance’, ‘heightened post-treatment platelet reactivity’ and ‘residual platelet reactivity’ have been introduced in the medical literature. Light transmittance aggregometry is generally considered to be the gold standard for determining platelet function, but its relevance to in vivo platelet function is questionable and the logistical demands of the method make it impossible to use in daily practice. The introduction of several point-of-care platelet function assays may be the key to the widespread clinical use of platelet function testing and may identify patients who are at risk for the occurrence of adverse cardiac events. In the present paper, we discuss the current commercially available methods of assaying platelet function, including their advantages and limitations and whether they have been shown to correlate with clinical outcomes.
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Affiliation(s)
- Jochem W van Werkum
- St Antonius Center for Platelet Function Research, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
| | - Christian M Hackeng
- St Antonius Center for Platelet Function Research, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
| | - Jaap-Jan J Smit
- Isala Klinieken, Department of Cardiology, Zwolle Groot Wezenland 20, 8011 JW Zwolle, The Netherlands
| | - Arnoud WJ van’t Hof
- Isala Klinieken, Department of Cardiology, Zwolle Groot Wezenland 20, 8011 JW Zwolle, The Netherlands
| | - Freek WA Verheugt
- University Medical Center St Radboud, Department of Cardiology, PO Box 9101, Nijmegen, The Netherlands
| | - Jurriën M ten Berg
- St Antonius Center for Platelet Function Research, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands
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Harrison P, Frelinger AL, Furman MI, Michelson AD. Measuring antiplatelet drug effects in the laboratory. Thromb Res 2007; 120:323-36. [PMID: 17239428 DOI: 10.1016/j.thromres.2006.11.012] [Citation(s) in RCA: 124] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2006] [Revised: 10/14/2006] [Accepted: 11/27/2006] [Indexed: 01/29/2023]
Abstract
This review discusses the advantages and disadvantages of currently available tests for the monitoring of antiplatelet therapy (especially aspirin and clopidogrel). Many tests of platelet function are now available for clinical use, and some of these tests have been shown to predict clinical outcomes after antiplatelet therapy. However, in most of these studies, the number of major adverse clinical events was low. No published studies address the clinical effectiveness of altering therapy based on the results of monitoring antiplatelet therapy. Therefore, the correct treatment, if any, of "resistance" to antiplatelet therapy is unknown and, other than in research trials, monitoring of antiplatelet therapy in patients is not generally recommended. A clinically meaningful definition of "resistance" to antiplatelet drugs needs to be developed, based on data linking drug-dependent laboratory tests to clinical outcomes in patients.
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Affiliation(s)
- Paul Harrison
- Oxford Haemophilia Centre and Thrombosis Unit, Churchill Hospital, Oxford, United Kingdom
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