Hamostaseologie 2009; 29(01): 25-31
DOI: 10.1055/s-0037-1616935
Original article
Schattauer GmbH

Assessment of platelet function in the laboratory

P. Harrison
1   Oxford Haemophilia & Thrombosis Centre, Churchill Hospital, Oxford, UK
› Author Affiliations
Further Information

Publication History

Publication Date:
29 December 2017 (online)

Summary

Platelet function testing is essential for the diagnosis of congenital/acquired bleeding disorders and may be useful for the prediction of surgical bleeding. Nowadays there is also much interest in monitoring the efficacy of anti-platelet therapy and measuring platelet hyper-function. However, this often presents clinical laboratories with significant challenges as platelet function tests are complex, poorly standardized, time consuming and quality assurance is not straightforward. There are also few comprehensive modern guidelines available and many recent published surveys have revealed poor standardization between laboratories.

Up until the late 1980’s the traditional clinical platelet function tests that were available were the bleeding time (BT), light transmission (LTA) and whole blood aggregometry (WBA) and various biochemical assays. These were also usually performed within specialized research and clinical laboratories. Since the last BCSH guidelines were published in 1988 a variety of new platelet function tests have become available. These include flow cytometry and an ever increasing choice of new commercial instruments. Although the potential clinical utility of the new assays is emerging some have not yet entered into routine clinical practice. It is encouraging that a number of standardization committees (e. g. CLSI, BCSH and ISTH Platelet Physiology SSC) are now beginning to produce new platelet function testing guidelines and this will hopefully improve clinical practice, quality assurance and result in less variability between different laboratories.

 
  • References

  • 1 Aleil B, Ravanat C, Cazenave JP. et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005; 3: 85-92.
  • 2 Armstrong PC, Truss NJ, Ali FY. et al. Aspirin and the in vitro linear relationship between thromboxane A(2) mediated platelet aggregation and platelet production of thromboxane A(2). J Thromb Haemost 2008; 6: 1933-1943.
  • 3 Bonello L, Camoin-Jau L, Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator- stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 2008; 51: 1404-1411.
  • 4 Cattaneo M. Are the bleeding time and PFA-100 useful in the initial screening of patients with mucocutaneous bleedings of hereditary nature?. J Thromb Haemost 2004; 2: 890-891.
  • 5 Chakroun T, Gerotziafas G, Robert F. et al. In vitro aspirin resistance detected by PFA-100 closure time: pivotal role of plasma von Willebrand factor. Br J Haematol 2004; 124: 80-85.
  • 6 Chen WH, Cheng X, Lee PY. et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med 2007; 120: 631-635.
  • 7 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.
  • 8 Elwood PC, Pickering J, Yarnell J. et al. Bleeding time, stroke and myocardial infarction: the Caerphilly prospective study. Platelets 2003; 14: 139-141.
  • 9 Favaloro EJ. Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations. Haemophilia 2001; 7: 170-179.
  • 10 Favaloro EJ. Clinical application of the PFA-100. Curr. Opin. Hematol 2002; 9: 407-415.
  • 11 Francis JL, Francis D, Larson L. et al. Can the platelet function analyser (PFA-100) substitute for the bleeding time in routine clinical practice. Platelets 1999; 10: 132-136.
  • 12 Frelinger III AL, Furman MI, Linden MD. et al. Aspirin resistance in a 700 patient study: residual arachidonic acid induced platelet activation via an adenosine diphosphate-dependent but cyclooxygenase- 1- and cyclooxygenase-2-independent pathway. Circulation 2006; 113: 2888-2896.
  • 13 Fressinaud E, Veyradier A, Truchaud F. et al. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood 1998; 91: 1325-1331.
  • 14 Frossard M, Fuchs I, Leitner JM. et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004; 110: 1392-1397.
  • 15 Fuchs I, Frossard M, Spiel A. et al. Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS. J Thromb Haemost 2006; 4: 2547-2552.
  • 16 Harrison P. Progress in the assessment of platelet function. Br J Haematol 2000; 111: 733-744.
  • 17 Harrison P. In vitro measurement of high-shear platelet adhesion and aggregation by the PFA-100. Methods Mol Biol 2004; 272: 215-223.
  • 18 Harrison P. Platelet function analysis. Blood Rev 2005; 19: 111-123.
  • 19 Harrison P, Frelinger III AL, Furman MI, Michelson AD. Measuring antiplatelet drug effects in the laboratory. Thromb Res 2007; 120: 323-336.
  • 20 Harrison P, Mackie I, Mathur A. et al. Platelet hyper-function in acute coronary syndromes. Blood Coagul Fibrinolysis 2005; 16: 557-562.
  • 21 Harrison P, Robinson M, Liesner R. et al. The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction. Clin Lab Haematol 2002; 24: 225-232.
  • 22 Hayward CP, Eikelboom J. Platelet function testing: quality assurance. Semin Thromb Hemost 2007; 33: 273-282.
  • 23 Hayward CP, Harrison P, Cattaneo M. et al. Platelet function analyser (PFA-100) closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4: 1-8.
  • 24 Homoncik M, Jilma B, Hergovich N. et al. Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100. Thromb Haemost 2000; 83: 316-321.
  • 25 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: 950-954.
  • 26 Jilma B. Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction. J Lab Clin Med 2001; 138: 152-163.
  • 27 Kereiakes DJ, Mueller M, Howard W. et al. Efficacy of abciximab induced platelet blockade using a rapid point of care assay. J Thromb Thrombolysis 1999; 7: 265-276.
  • 28 Koscielny J, Ziemer S, Radtke H. et al. A practical concept for preoperative identification of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10: 195-204.
  • 29 Kottke-Marchant K, Corcoran G. The laboratory diagnosis of platelet disorders. Arch Pathol Lab Med 2002; 126: 133-146.
  • 30 Kundu SK, Heilmann EJ, Sio R. et al. Description of an in vitro platelet function analyzer--PFA-100. Semin Thromb Hemost 1995; 21: 106-112.
  • 31 Lind SE. The Bleeding Time. In: Michelson AD. ed. Platelets. San Diego: Academic Press;; 2002: 283-289.
  • 32 Malinin A, Pokov A, Spergling M. et al. Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: The VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res 2006; 119: 277-284.
  • 33 Malinin A, Pokov A, Swaim L. et al. Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel. Methods Find Exp Clin Pharmacol 2006; 28: 315-322.
  • 34 Michelson AD. Flow cytometry: a clinical test of platelet function. Blood 1996; 87: 4925-4936.
  • 35 Michelson AD, Linden M, Barnard MR. et al. Flow Cytometry. In: Michelson AD. ed. Platelets. Academic Press; 2007: 545-563.
  • 36 Michelson AD, Linden MD, Furman MI. et al. Evidence that pre-existent variability in platelet response to ADP accounts for „clopidogrel resistance“. J Thromb Haemost 2007; 5: 75-81.
  • 37 Mielke CH. Measurement of the bleeding time. Thromb Haemost 1984; 52: 210-211.
  • 38 Moffat KA, Ledford-Kraemer MR, Nichols WL, Hayward CP. 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.
  • 39 Moran N, Kiernan A, Dunne E. et al. Monitoring modulators of platelet aggregation in a microtiter plate assay. Anal Biochem 2006; 357: 77-84.
  • 40 Peace AJ, Tedesco AF, Foley DP. et al. Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with coronary artery disease. J Thromb Haemost 2008; 6: 2027-2034.
  • 41 Podda GM, Bucciarelli P, Lussana F. et al. Usefulness of PFA-100 testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time. J Thromb Haemost 2007; 5: 2393-2398.
  • 42 Price MJ, Endemann S, Gollapudi RR. et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008; 29: 992-1000.
  • 43 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.
  • 44 Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost 1990; 16: 1-20.
  • 45 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: 885-896.
  • 46 Smith JW, Steinhubl SR, Lincoff AM. et al. Rapid platelet-function assay: an automated and quantitative cartridge-based method. Circulation 1999; 99: 620-625.
  • 47 Steinhubl S. The VerifyNow System. In: Michelson AD. ed. Platelets. San Diego: Academic Press;; 2007: 509-518.
  • 48 Steinhubl SR, Talley JD, Braden GA. et al. Pointof- 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.
  • 49 The British Society for Haematology BCSH Haemo stasis and Thrombosis Task Force.. Guidelines on platelet function testing. J Clin Pathol 1988; 41: 1322-1330.
  • 50 Varon D, Savion N. Impact Cone and Plate(let) Analyzer. In: Michelson AD. ed. Platelets. San Diego: Academic Press;; 2007: 535-544.
  • 51 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: 1492-1494.