Subscribe to RSS
DOI: 10.1055/s-0035-1564834
Platelet Function Tests
Publication History
Publication Date:
29 February 2016 (online)
Abstract
Traditionally developed for diagnosis of bleeding disorders, platelet function assays have become increasingly used in basic research on platelet physiology, in phenotype–genotype associations in bleeding disorders, in drug development as surrogate endpoints of efficacy of new antiplatelet therapy, and to an extent, in the monitoring of antiplatelet therapy in clinical practice to predict thrombotic and bleeding risk. A multiplicity of platelet function assays is available to measure the level of platelet activity in various settings. These include assays that are restricted to a specialized laboratory as well as point-of-care instruments meant to investigate platelet function at patient bedside. Unlike tests that determine a defined quantity or measurement of a clinical biomarker (e.g., cholesterol or blood pressure), platelet function testing assesses the dynamics of living cells, which immediately presents a series of unique problems to any laboratory or clinic. This article presents currently used platelet function assays and discusses important variables to take into account when performing these assays, including preanalytical issues and difficulties in interpreting platelet function test results.
-
References
- 1 Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011; 105 (Suppl. 01) S13-S33
- 2 McFadyen JD, Kaplan ZS. Platelets are not just for clots. Transfus Med Rev 2015; 29 (2) 110-119
- 3 Gremmel T, Frelinger III AL, Michelson AD. Platelet physiology. Semin Thromb Hemost 2016; 42 (3) 191-204
- 4 Gresele P ; Subcommittee on Platelet Physiology. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost 2015; 13 (2) 314-322
- 5 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115 (12) 3378-3384
- 6 Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8 (11) 1227-1234
- 7 Siller-Matula JM, Trenk D, Schrör K , et al; European Platelet Academy. How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors—is an algorithm the answer?. Thromb Haemost 2015; 113 (1) 37-52
- 8 Petricevic M, Kopjar T, Biocina B , et al. The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: a systematic review. Thorac Cardiovasc Surg 2015; 63 (1) 2-20
- 9 Gresele P, Bury L, Falcinelli E. Inherited platelet function disorders: algorithms for phenotypic and genetic investigation. Semin Thromb Hemost 2016; 42 (3) 292-305
- 10 Cai H, Mullier F, Frotscher B , et al. Usefulness of flow cytometric mepacrine uptake/release combined with CD63 assay in diagnosis of patients with suspected platelet dense granule disorder. Semin Thromb Hemost 2016; 42 (3) 282-291
- 11 Gross L, Aradi D, Sibbing D. Platelet function testing in patients on antiplatelet medications. Semin Thromb Hemost 2016; 42 (3) 306-320
- 12 Milian MG. Technique pour l'étude clinique de la coagulation du sang. Bull Mem Soc Med Hop Paris 1901; 18: 777-783
- 13 Duke WW. The relation of blood platelets to hemorrhagic disease. Description of a method for determining the bleeding time and the coagulation time and report of three cases of hemorrahagic disease relieved by blood transfusion. JAMA 1910; 55: 1185-1192
- 14 Ivy AC, Nelson D, Bucher G. The standardization of certain factors in the cutaneous “venostasis” bleeding time technique. J Lab Clin Med 1941; 26: 1812-1822
- 15 Mielke Jr CH, Kaneshiro MM, Maher IA, Weiner JM, Rapaport SI. The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 1969; 34 (2) 204-215
- 16 The British Society for Haematology BCSH Haemostasis and Thrombosis Task Force. Guidelines on platelet function testing. J Clin Pathol 1988; 41 (12) 1322-1330
- 17 Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost 1990; 16 (1) 1-20
- 18 Lind SE. The bleeding time does not predict surgical bleeding. Blood 1991; 77 (12) 2547-2552
- 19 Peterson P, Hayes TE, Arkin CF , 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 (2) 134-139
- 20 Harrison P, Mackie I, Mumford A , et al; British Committee for Standards in Haematology. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155 (1) 30-44
- 21 Moffat KA, Ledford-Kraemer MR, Nichols WL, Hayward CP ; North American Specialized Coagulation Laboratory Association. 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 (3) 549-553
- 22 Jennings I, Woods TA, Kitchen S, Walker ID. Platelet function testing: practice among UK National External Quality Assessment Scheme for Blood Coagulation participants, 2006. J Clin Pathol 2008; 61 (8) 950-954
- 23 Cattaneo M, Hayward CP, Moffat KA, Pugliano MT, Liu Y, Michelson AD. Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH. J Thromb Haemost 2009; 7 (6) 1029
- 24 Gresele P, Harrison P, Bury L , et al. Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey. J Thromb Haemost 2014; 12 (9) 1562-1569
- 25 Favaloro EJ. Time for a conceptual shift in assessment of internal quality control for whole blood or cell-based testing systems? An evaluation using platelet function and the PFA-100 as a case example. Clin Chem Lab Med 2013; 51 (4) 767-774
- 26 Favaloro EJ, Bonar R. External quality assessment/proficiency testing and internal quality control for the PFA-100 and PFA-200: an update. Semin Thromb Hemost 2014; 40 (2) 239-253
- 27 Favaloro EJ. Internal quality control and external quality assurance of platelet function tests. Semin Thromb Hemost 2009; 35 (2) 139-149
- 28 Harrison P, Lordkipanidzé M. Testing platelet function. Hematol Oncol Clin North Am 2013; 27 (3) 411-441
- 29 Hartley PS. The diurnal tick-tockery of platelet biology. Platelets 2012; 23 (2) 157-160
- 30 Davis RB, Boyd DG, McKinney ME, Jones CC. Effects of exercise and exercise conditioning on blood platelet function. Med Sci Sports Exerc 1990; 22 (1) 49-53
- 31 Ahuja KD, Adams MJ, Robertson IK, Ball MJ. Acute effect of a high-carbohydrate low-fat meal on platelet aggregation. Platelets 2009; 20 (8) 606-609
- 32 Natella F, Nardini M, Belelli F , et al. Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation. Br J Nutr 2008; 100 (6) 1276-1282
- 33 Varani K, Portaluppi F, Gessi S , et al. Dose and time effects of caffeine intake on human platelet adenosine A(2A) receptors : functional and biochemical aspects. Circulation 2000; 102 (3) 285-289
- 34 Rival J, Riddle JM, Stein PD. Effects of chronic smoking on platelet function. Thromb Res 1987; 45 (1) 75-85
- 35 Kottke-Marchant K, Corcoran G. The laboratory diagnosis of platelet disorders. Arch Pathol Lab Med 2002; 126 (2) 133-146
- 36 Cattaneo M, Cerletti C, Harrison P , et al. Recommendations for the standardization of light transmission aggregometry: A consensus of the working party from the platelet physiology subcommittee of SSC/ISTH. J Thromb Haemost 2013; 11: 1183-1189
- 37 Favaloro EJ, Lippi G, Adcock DM. Preanalytical and postanalytical variables: the leading causes of diagnostic error in hemostasis?. Semin Thromb Hemost 2008; 34 (7) 612-634
- 38 Kaiser AF, Neubauer H, Franken CC, Krüger JC, Mügge A, Meves SH. Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions. Platelets 2012; 23 (5) 359-367
- 39 Thalén S, Forsling I, Eintrei J, Söderblom L, Antovic JP. Pneumatic tube transport affects platelet function measured by multiplate electrode aggregometry. Thromb Res 2013; 132 (1) 77-80
- 40 Femia EA, Pugliano M, Podda G, Cattaneo M. Comparison of different procedures to prepare platelet-rich plasma for studies of platelet aggregation by light transmission aggregometry. Platelets 2012; 23 (1) 7-10
- 41 Linnemann B, Schwonberg J, Mani H, Prochnow S, Lindhoff-Last E. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary. J Thromb Haemost 2008; 6 (4) 677-683
- 42 Cattaneo M, Lecchi A, Zighetti ML, Lussana F. Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count. Haematologica 2007; 92 (5) 694-697
- 43 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
- 44 Pai M, Wang G, Moffat KA , et al. Diagnostic usefulness of a lumi-aggregometer adenosine triphosphate release assay for the assessment of platelet function disorders. Am J Clin Pathol 2011; 136 (3) 350-358
- 45 Hayward CP, Moffat KA, Raby A , et al. Development of North American consensus guidelines for medical laboratories that perform and interpret platelet function testing using light transmission aggregometry. Am J Clin Pathol 2010; 134 (6) 955-963
- 46 Cazenave JP, Ohlmann P, Cassel D, Eckly A, Hechler B, Gachet C. Preparation of washed platelet suspensions from human and rodent blood. Methods Mol Biol 2004; 272: 13-28
- 47 Dawood BB, Lowe GC, Lordkipanidzé M , et al. Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel. Blood 2012; 120 (25) 5041-5049
- 48 Lawrie AS, Kobayashi K, Lane PJ, Mackie IJ, Machin SJ. The automation of routine light transmission platelet aggregation. Int J Lab Hematol 2014; 36 (4) 431-438
- 49 Sun B, Tandon NN, Yamamoto N, Yoshitake M, Kambayashi J. Luminometric assay of platelet activation in 96-well microplate. Biotechniques 2001; 31 (5) 1174 , 1176, 1178 passim
- 50 Moran N, Kiernan A, Dunne E, Edwards RJ, Shields DC, Kenny D. Monitoring modulators of platelet aggregation in a microtiter plate assay. Anal Biochem 2006; 357 (1) 77-84
- 51 Chan MV, Armstrong PC, Papalia F, Kirkby NS, Warner TD. Optical multichannel (optimul) platelet aggregometry in 96-well plates as an additional method of platelet reactivity testing. Platelets 2011; 22 (7) 485-494
- 52 Chan MV, Warner TD. Standardised optical multichannel (optimul) platelet aggregometry using high-speed shaking and fixed time point readings. Platelets 2012; 23 (5) 404-408
- 53 Lordkipanidzé M, Lowe GC, Kirkby NS , et al; UK Genotyping and Phenotyping of Platelets Study Group. Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay. Blood 2014; 123 (8) e11-e22
- 54 Mylotte D, Kavanagh GF, Peace AJ , et al. Platelet reactivity in type 2 diabetes mellitus: a comparative analysis with survivors of myocardial infarction and the role of glycaemic control. Platelets 2012; 23 (6) 439-446
- 55 Cooke NM, Egan K, McFadden S , et al. Increased platelet reactivity in patients with late-stage metastatic cancer. Cancer Med 2013; 2 (4) 564-570
- 56 Cardinal DC, Flower RJ. The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Pharmacol Methods 1980; 3 (2) 135-158
- 57 Solomon C, Traintinger S, Ziegler B , et al. Platelet function following trauma. A multiple electrode aggregometry study. Thromb Haemost 2011; 106 (2) 322-330
- 58 Valarche V, Desconclois C, Boutekedjiret T, Dreyfus M, Proulle V. Multiplate whole blood impedance aggregometry: a new tool for von Willebrand disease. J Thromb Haemost 2011; 9 (8) 1645-1647
- 59 Aradi D, Storey RF, Komócsi A , et al; Working Group on Thrombosis of the European Society of Cardiology. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35 (4) 209-215
- 60 Würtz M, Hvas AM, Christensen KH, Rubak P, Kristensen SD, Grove EL. Rapid evaluation of platelet function using the Multiplate® Analyzer. Platelets 2014; 25 (8) 628-633
- 61 Rubak P, Villadsen K, Hvas AM. Reference intervals for platelet aggregation assessed by multiple electrode platelet aggregometry. Thromb Res 2012; 130 (3) 420-423
- 62 Stissing T, Dridi NP, Ostrowski SR, Bochsen L, Johansson PI. The influence of low platelet count on whole blood aggregometry assessed by Multiplate. Clin Appl Thromb Hemost 2011; 17 (6) E211-E217
- 63 Kong R, Trimmings A, Hutchinson N , et al. Consensus recommendations for using the Multiplate(®) for platelet function monitoring before cardiac surgery. Int J Lab Hematol 2015; 37 (2) 143-147
- 64 Albanyan A, Al-Musa A, AlNounou R , et al. Diagnosis of Glanzmann thrombasthenia by whole blood impedance analyzer (MEA) vs. light transmission aggregometry. Int J Lab Hematol 2015; 37 (4) 503-508
- 65 Wang JC, Aucoin-Barry D, Manuelian D , et al. Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay-ASA. Am J Cardiol 2003; 92 (12) 1492-1494
- 66 van Werkum JW, Harmsze AM, Elsenberg EH, Bouman HJ, ten Berg JM, Hackeng CM. The use of the VerifyNow system to monitor antiplatelet therapy: a review of the current evidence. Platelets 2008; 19 (7) 479-488
- 67 Scavone M, Germanovich K, Femia EA, Cattaneo M. Usefulness of the INNOVANCE PFA P2Y test cartridge for the detection of patients with congenital defects of the platelet P2Y12 receptor for adenosine diphosphate. Thromb Res 2014; 133 (2) 254-256
- 68 Koessler J, Ehrenschwender M, Kobsar A, Brunner K. Evaluation of the new INNOVANCE® PFA P2Y cartridge in patients with impaired primary haemostasis. Platelets 2012; 23 (8) 571-578
- 69 Koessler J, Kobsar AL, Rajkovic MS , et al. The new INNOVANCE® PFA P2Y cartridge is sensitive to the detection of the P2Y12 receptor inhibition. Platelets 2011; 22 (1) 20-27
- 70 Edwards A, Jakubowski JA, Rechner AR, Sugidachi A, Harrison P. Evaluation of the INNOVANCE PFA P2Y test cartridge: sensitivity to P2Y(12) blockade and influence of anticoagulant. Platelets 2012; 23 (2) 106-115
- 71 Carcao MD, Blanchette VS, Stephens D , et al. Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100). Br J Haematol 2002; 117 (4) 961-964
- 72 Cho YU, Jang S, Park CJ, Chi HS. Variables that affect platelet function analyzer-100 (PFA-100) closure times and establishment of reference intervals in Korean adults. Ann Clin Lab Sci 2008; 38 (3) 247-253
- 73 Jilma B. Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction. J Lab Clin Med 2001; 138 (3) 152-163
- 74 Favaloro EJ. Clinical application of the PFA-100. Curr Opin Hematol 2002; 9 (5) 407-415
- 75 Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost 2008; 34 (8) 709-733
- 76 Hayward CP, Harrison P, Cattaneo M, Ortel TL, Rao AK ; Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4 (2) 312-319
- 77 Chen A, Teruya J. Global hemostasis testing thromboelastography: old technology, new applications. Clin Lab Med 2009; 29 (2) 391-407
- 78 Luddington RJ. Thromboelastography/thromboelastometry. Clin Lab Haematol 2005; 27 (2) 81-90
- 79 Blais N, Pharand C, Lordkipanidzé M, Sia YK, Merhi Y, Diodati JG. Response to aspirin in healthy individuals. Cross-comparison of light transmission aggregometry, VerifyNow system, platelet count drop, thromboelastography (TEG) and urinary 11-dehydrothromboxane B(2). Thromb Haemost 2009; 102 (2) 404-411
- 80 Scharbert G, Auer A, Kozek-Langenecker S. Evaluation of the Platelet Mapping Assay on rotational thromboelastometry ROTEM. Platelets 2009; 20 (2) 125-130
- 81 Chitlur M, Lusher J. Standardization of thromboelastography: values and challenges. Semin Thromb Hemost 2010; 36 (7) 707-711
- 82 Ramström S, Södergren AL, Tynngård N, Lindahl TL. Platelet function determined by flow cytometry: new perspectives?. Semin Thromb Hemost 2016; 42 (3) 268-281
- 83 Rubak P, Nissen PH, Kristensen SD, Hvas AM. Investigation of platelet function and platelet disorders using flow cytometry. Platelets 2016; 27 (1) 66-74
- 84 Schmitz G, Rothe G, Ruf A , et al. European Working Group on Clinical Cell Analysis: Consensus protocol for the flow cytometric characterisation of platelet function. Thromb Haemost 1998; 79 (5) 885-896
- 85 Matzdorff A. Platelet function tests and flow cytometry to monitor antiplatelet therapy. Semin Thromb Hemost 2005; 31 (4) 393-399
- 86 Frelinger III AL, Grace RF, Gerrits AJ , et al. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. Blood 2015; 126 (7) 873-879
- 87 Lee JA, Spidlen J, Boyce K , et al; International Society for Advancement of Cytometry Data Standards Task Force. MIFlowCyt: the minimum information about a Flow Cytometry Experiment. Cytometry A 2008; 73 (10) 926-930
- 88 Coller BS. Historical perspective and future directions in platelet research. J Thromb Haemost 2011; 9 (Suppl. 01) 374-395
- 89 Michelson AD. Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov 2010; 9 (2) 154-169
- 90 Aradi D, Kirtane A, Bonello L , et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36 (27) 1762-1771
- 91 de Witt SM, Swieringa F, Cavill R , et al. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nat Commun 2014; 5: 4257