Platelet Function Testing: Quality Assurance

ABSTRACT

Platelet function tests are widely used for the diagnosis of platelet disorders. In recent years there has been increasing interest in the use of platelet function tests to monitor antiplatelet drug therapy. Quality assurance is important to optimize the performance of laboratory assays but it has not been widely applied to platelet function tests. This deficiency likely reflects the need to use freshly collected blood samples for platelet function tests, and the complex, time-consuming nature of some assays such as aggregation studies. Platelet function testing lacks guidelines, is poorly standardized between laboratories, and rarely is evaluated by internal and external quality assurance exercises. The sensitivity, specificity, and diagnostic utility of some newer, simplified assays of platelet function have been evaluated in a range of clinical settings but corresponding quality assurance data for many established as well as emerging platelet function assays are lacking. Quality assurance issues relevant to testing platelet function are reviewed in this article, with a focus on their application to established and to new and emerging tests.

KEYWORDS

Platelet function testing - quality assurance - platelet disorders - platelet aggregation - platelet secretion - Platelet Function Analyzer-100 closure time - bleeding time

REFERENCES

• 1 Hayward C P, Rao A K, Cattaneo M. Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment.  Haemophilia. 2006;  12(suppl 3) 128-136
• 2 Michelson A D, Cattaneo M, Eikelboom J W et al.. Aspirin resistance: position paper of the Working Group on Aspirin Resistance.  J Thromb Haemost. 2005;  3 1309-1311
• 3 Hayward C P, Harrison P, Cattaneo M, Ortel T L, Rao A K. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function.  J Thromb Haemost. 2006;  4 312-319
• 4 Moffat K A, Ledford-Kraemer M R, Nichols W L, Hayward C P. Variability in clinical laboratory practice in testing for disorders of platelet function: results of two surveys of the North American Specialized Coagulation Laboratory Association.  Thromb Haemost. 2005;  93 549-553
• 5 Clark G B. Quality assurance, an administrative means to a managerial end: Part I. A historical overview.  Clin Lab Manage Rev. 1990;  4 7-15
• 6 Nichols J H, Poe S S. Quality assurance, practical management, and outcomes of point-of-care testing: laboratory perspectives, Part I.  Clin Lab Manage Rev. 1999;  13 341-350
• 7 Dybkaer R. Quality assurance, accreditation, and certification: needs and possibilities.  Clin Chem. 1994;  40 1416-1420
• 8 Uldall A. Quality assurance in clinical laboratories. An updated supplement to a bibliography.  Eur J Haematol Suppl. 1990;  53 22-37
• 9 May J A, Heptinstall S. Effects of anticoagulants used during blood collection on human platelet function.  Methods Mol Biol. 2004;  272 3-11
• 10 Guidelines on platelet function testing. The British Society for Hematology, BCSH Haemostasis and Thrombosis Task Force.  J Clin Pathol. 1988;  41 1322-1330
• 11 Breddin H K. Can platelet aggregometry be standardized?.  Platelets. 2005;  16 151-158
• 12 Cunningham M T, Brandt J T, Chandler W L et al.. Quality assurance in hemostasis: the perspective from the College of American Pathologists Proficiency Testing Program.  Semin Thromb Hemost. 2007;  33 249-258
• 13 Bowbrick V A, Mikhailidis D P, Stansby G. Influence of platelet count and activity on thromboelastography parameters.  Platelets. 2003;  14 219-224
• 14 Agarwal S, Coakely M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy: a comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry.  Anesthesiology. 2006;  105 676-683
• 15 Lombard F W, Welsby I J, Alexander M J, Borel C O. Thromboelastography detects inadequate response to abciximab therapy during stent-assisted cerebral aneurysm coil embolization complicated by stroke.  Neurocrit Care. 2006;  4 32-34
• 16 Diamandis M, Adam F, Kahr W H et al.. Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.  J Thromb Haemost. 2006;  4 1086-1094
• 17 Sweeney J D, Hoernig L A, Michnik A, Fitzpatrick J E. Whole blood aggregometry. Influence of sample collection and delay in study performance on test results.  Am J Clin Pathol. 1989;  92 676-679
• 18 Tiffany M L. Technical considerations for platelet aggregation and related problems.  Crit Rev Clin Lab Sci. 1983;  19 27-69
• 19 Jhang J S, Spitalnik S L. Glycosylation and cold platelet storage.  Curr Hematol Rep. 2005;  4 483-487
• 20 Favaloro E J. Clinical application of the PFA-100.  Curr Opin Hematol. 2002;  9 407-415
• 21 Lind S E. The bleeding time. In: Michelson AD Platelets. San Diego, CA; Academic Press 2002: 283-289
• 22 Peterson P, Hayes T E, Arkin C F et al.. The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.  Arch Surg. 1998;  133 134-139
• 23 Gewirtz A S, Miller M L, Keys T F. The clinical usefulness of the preoperative bleeding time.  Arch Pathol Lab Med. 1996;  120 353-356
• 24 Rodgers R P, Levin J. A critical reappraisal of the bleeding time.  Semin Thromb Hemost. 1990;  16 1-20
• 25 Barber A, Green D, Galluzzo T, Ts'ao C H. The bleeding time as a preoperative screening test.  Am J Med. 1985;  78 761-764
• 26 Hampton K K, Cerletti C, Loizou L A et al.. Coagulation, fibrinolytic and platelet function in patients on long-term therapy with aspirin 300 mg or 1,200 mg daily compared with placebo.  Thromb Haemost. 1990;  64 17-20
• 27 Quiroga T, Goycoolea M, Munoz B et al.. Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients.  J Thromb Haemost. 2004;  2 892-898
• 28 Hertfelder H J, Bos M, Weber D et al.. Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting.  Semin Thromb Hemost. 2005;  31 426-440
• 29 Fox S C, Sasae R, Janson S, May J A, Heptinstall S. Quantitation of platelet aggregation and microaggregate formation in whole blood by flow cytometry.  Platelets. 2004;  15 85-93
• 30 Storey R F, May J A, Wilcox R G, Heptinstall S. A whole blood assay of inhibition of platelet aggregation by glycoprotein IIb/IIIa antagonists: comparison with other aggregation methodologies.  Thromb Haemost. 1999;  82 1307-1311
• 31 Burgess-Wilson M E, Cockbill S R, Johnston G I, Heptinstall S. Platelet aggregation in whole blood from patients with Glanzmann's thrombasthenia.  Blood. 1987;  69 38-42
• 32 Falcon C, Arnout J, Vermylen J. Platelet aggregation in whole blood-studies with a platelet counting technique-methodological aspects and some applications.  Thromb Haemost. 1989;  61 423-428
• 33 Mani H, Luxembourg B, Klaffling C, Erbe M, Lindhoff-Last E. Use of native or platelet count adjusted platelet rich plasma for platelet aggregation measurements.  J Clin Pathol. 2005;  58 747-750
• 34 Riess H, Braun G, Brehm G, Hiller E. Critical evaluation of platelet aggregation in whole human blood.  Am J Clin Pathol. 1986;  85 50-56
• 35 Zwierzina W D, Kunz F, Kogelnig R, Herold M. Sex-related differences in platelet aggregation in native whole blood.  Thromb Res. 1987;  48 161-171
• 36 Geiger J, Teichmann L, Grossmann R et al.. Monitoring of clopidogrel action: comparison of methods.  Clin Chem. 2005;  51 957-965
• 37 Mobley J E, Bresee S J, Wortham D C et al.. Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization.  Am J Cardiol. 2004;  93 456-458
• 38 Burns T L, Mooss A N, Hilleman D E. Antiplatelet drug resistance: not ready for prime time.  Pharmacotherapy. 2005;  25 1621-1628
• 39 Wall J E, Buijs-Wilts M, Arnold J T et al.. A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents.  Br J Haematol. 1995;  89 380-385
• 40 Harrison P, Segal H, Blasbery K et al.. Screening for aspirin responsiveness after transient ischemic attack and stroke: comparison of 2 point-of-care platelet function tests with optical aggregometry.  Stroke. 2005;  36 1001-1005
• 41 Hezard N, Metz D, Garnotel R et al.. Platelet VASP phosphorylation assessment in clopidogrel-treated patients: lack of agreement between Western blot and flow cytometry.  Platelets. 2005;  16 474-481
• 42 Rand M L, Leung R, Packham M A. Platelet function assays.  Transfus Apher Sci. 2003;  28 307-317
• 43 Eikelboom J W, Hankey G J. Failure of aspirin to prevent atherothrombosis: potential mechanisms and implications for clinical practice.  Am J Cardiovasc Drugs. 2004;  4 57-67
• 44 Eikelboom J W, Hirsh J, Weitz J I 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
• 45 Maree A O, Curtin R J, Dooley M et al.. Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease.  J Am Coll Cardiol. 2005;  46 1258-1263
• 46 Patrono C, Ciabattoni G, Pugliese F et al.. Radioimmunoassay of serum thromboxane B2: a simple method of assessing pharmacologic effects on platelet function.  Adv Prostaglandin Thromboxane Res. 1980;  6 187-191
• 47 Van Cott E M. Coagulation point-of-care testing.  Clin Lab Med. 2001;  21 337-350
• 48 White M M, Krishnan R, Kueter T J, Jacoski M V, Jennings L K. The use of the point of care Helena ICHOR/Plateletworks and the Accumetrics Ultegra RPFA for assessment of platelet function with GPIIB-IIIa antagonists.  J Thromb Thrombolysis. 2004;  18 163-169
• 49 Wheeler G L, Braden G A, Steinhubl S R et al.. The Ultegra rapid platelet-function assay: comparison to standard platelet function assays in patients undergoing percutaneous coronary intervention with abciximab therapy.  Am Heart J. 2002;  143 602-611
• 50 Danzi G B, Capuano C, Sesana M, Baglini R. Preliminary experience with a high bolus dose of tirofiban during percutaneous coronary intervention.  Curr Med Res Opin. 2003;  19 28-33
• 51 Malinin A, Spergling M, Muhlestein B, Steinhubl S, Serebruany V. Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer.  Blood Coagul Fibrinolysis. 2004;  15 295-301
• 52 Selvaraj C L, Van De Graaff E J, Campbell C L et al.. Point-of-care determination of baseline platelet function as a predictor of clinical outcomes in patients who present to the emergency department with chest pain.  J Thromb Thrombolysis. 2004;  18 109-115
• 53 Koscielny J, Aslan T, Meyer O et al.. Use of the platelet reactivity index by Grotemeyer, platelet function analyzer, and retention test Homburg to monitor therapy with antiplatelet drugs.  Semin Thromb Hemost. 2005;  31 464-469
• 54 Craft R M, Chavez J J, Snider C C, Muenchen R A, Carroll R C. Comparison of modified thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients.  J Lab Clin Med. 2005;  145 309-315
• 55 Ostrowsky J, Foes J, Warchol M, Tsarovsky G, Blay J. Plateletworks platelet function test compared to the thromboelastograph for prediction of postoperative outcomes.  J Extra Corpor Technol. 2004;  36 149-152
• 56 Lennon M J, Gibbs N M, Weightman W M, McGuire D, Michalopoulos N. A comparison of Plateletworks and platelet aggregometry for the assessment of aspirin-related platelet dysfunction in cardiac surgical patients.  J Cardiothorac Vasc Anesth. 2004;  18 136-140
• 57 Ray M J, Walters D L, Bett N et al.. Point-of-care testing shows clinically relevant variation in the degree of inhibition of platelets by standard-dose abciximab therapy during percutaneous coronary intervention.  Catheter Cardiovasc Interv. 2004;  62 150-154
• 58 Isgro F, Rehn E, Kiessling A H et al.. Platelet function test HemoSTATUS 2: tool or toy for an optimized management of hemostasis?.  Perfusion. 2002;  17 27-31
• 59 Saleem R, Bigham M, Spitznagel E, Despotis G J. The effect of epsilon-aminocaproic acid on HemoSTATUS and kaolin-activated clotting time measurements.  Anesth Analg. 2000;  90 1281-1285
• 60 Coiffic A, Cazes E, Janvier G et al.. Inhibition of platelet aggregation by abciximab but not by aspirin can be detected by a new point-of-care test, the hemostatus.  Thromb Res. 1999;  95 83-91
• 61 Ereth M H, Nuttall G A, Santrach P J et al.. The relation between the platelet-activated clotting test (HemoSTATUS) and blood loss after cardiopulmonary bypass.  Anesthesiology. 1998;  88 962-969
• 62 Ereth M H, Nuttall G A, Klindworth J T et al.. Does the platelet-activated clotting test (HemoSTATUS) predict blood loss and platelet dysfunction associated with cardiopulmonary bypass?.  Anesth Analg. 1997;  85 259-264
• 63 Savion N, Varon D. Impact-the cone and plate(let) analyzer: testing platelet function and anti-platelet drug response.  Pathophysiol Haemost Thromb. 2006;  35 83-88
• 64 Szarvas M, Oparaugo P, Udvardy M L et al.. Differential platelet deposition onto collagen in cone-and-plate and parallel plate flow chambers.  Platelets. 2006;  17 185-190
• 65 Spectre G, Brill A, Gural A et al.. A new point-of-care method for monitoring anti-platelet therapy: application of the cone and plate(let) analyzer.  Platelets. 2005;  16 293-299
• 66 Bailey L A, Sistino J J, Uber W E. Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors?.  J Extra Corpor Technol. 2005;  37 43-47
• 67 Katori N, Tanaka K A, Szlam F, Levy J H. The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography.  Anesth Analg. 2005;  100 1781-1785