Semin Thromb Hemost 2009; 35(2): 168-180
DOI: 10.1055/s-0029-1220325
© Thieme Medical Publishers

Whole Blood Platelet Aggregometry and Platelet Function Testing

David L. McGlasson1 , George A. Fritsma2
  • 1Wilford Hall Medical Center, United States Air Force Lackland AFB, Texas
  • 2The Fritsma Factor, Your Interactive Hemostasis Resource Clinical Associate Professor, Pathology University of Alabama at Birmingham, Birmingham, Alabama
Further Information

Publication History

Publication Date:
30 April 2009 (online)

ABSTRACT

Platelet aggregometry has been the reference method employed to detect, diagnose, and monitor qualitative platelet disorders since the early 1960s. Lumiaggregometry and impedance-based whole blood lumiaggregometry have advantages over light transmittance aggregometry in that they provide for enhanced specimen management and increase the test sensitivity to impairment of platelet granule secretion. Whole blood lumiaggregometry detects and identifies congenital and acquired platelet plasma membrane receptor defects, metabolic pathway secretion disorders, and storage pool deficiency. Whole blood lumiaggregometry is also being applied to antiplatelet therapy monitoring and identifies aspirin and thienopyridine resistance. There is growing interest in using impedance-based whole blood lumiaggregometry for near-patient whole blood platelet analysis and antiplatelet therapy monitoring. This article will also discuss other whole blood testing processes for assessing platelet function, particularly as applied to assessing the effect of antiplatelet medication.

REFERENCES

  • 1 Jacobs K. Platelet function testing.  Advance. 1999;  56-59
  • 2 Fritsma G. An overview of clinical laboratory hematology. In: Rodak BF, Fritsma GA, Doig K Hematology: Clinical Principles and Applications. St. Louis, MI; Elsevier 2007: 1-6
  • 3 Born G VR. Quantitative investigations into the aggregation of blood platelets.  J Physiol. 1962;  162 67-68
  • 4 Born G V, Cross M J. The aggregation of blood platelets.  J Physiol. 1963;  168 178-195
  • 5 Harrison P, Mumford A. Screening tests of platelet function: update on their appropriate uses for diagnostic testing.  Semin Thromb Hemost. 2009;  35 150-157
  • 6 Cattaneo M. Light transmission aggregometry and ATP release for the diagnostic assessment of platelet function.  Semin Thromb Hemost. 2009;  35 158-167
  • 7 Cardinal D C, Flower R J. The electronic aggregometer: a novel device for assessing platelet behavior in blood.  J Pharmacol Methods. 1980;  3(2) 135-158
  • 8 Ingerman-Wojenski C M, Silver M J. A quick method for screening platelet dysfunctions using the whole blood lumi-aggregometer.  Thromb Haemost. 1984;  51 154-156
  • 9 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;  6 677-683
  • 10 Ciruela F. Fluorescence-based methods in the study of protein-protein interactions in living cells.  Curr Opin Biotechnol. 2008;  19 338-343
  • 11 Viviani V R. The origin, diversity, and structure function relationships of insect luciferases.  Cell Mol Life Sci. 2002;  59 1833-1850
  • 12 Feinman R D, Detwiler T C, Ingerman-Wojenski C. The lumi-aggregometer as a research and clinical tool. In: Longenecker GL The Platelets; Physiology and Pharmacology. New York, NY; Academic Press 1985: 429-440
  • 13 Blackwell G J, Flower R J, Russell-Smith N et al.. Prostacyclin is produced in whole blood.  Br J Pharmacol. 1978;  64 436
  • 14 Sweeney J D, Labuzetta J W, Fitzpatrick J E. The effect of the platelet count on the aggregation response and adenosine triphosphate release in an impedance lumi-aggregometer.  Am J Clin Pathol. 1988;  89 655-659
  • 15 Dyszkiewicz-Korpanty A M, Frenkel E P, Sarode R. Approach to the assessment of platelet function: comparison between optical-based platelet-rich plasma and impedance-based whole blood platelet aggregation methods.  Clin Appl Thromb Hemost. 2005;  11 25-35
  • 16 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
  • 17 Christie D J, Avari T, Carrington L R Platelet Function Testing by Aggregometry et al.. Approved Guideline. CLSI document H58-A. Wayne, PA; Clinical and Laboratory Standards Institute (CLSI) 2008
  • 18 Brace L D. Qualitative disorders of platelets and vasculature. In: Rodak BF, Fritsma GA, Doig K Hematology: Clinical Principles and Applications, 3rd ed. New York, NY; Elsevier 2007: 654-669
  • 19 Nurden A T, George J N. Inherited abnormalities of the platelet membrane: Glanzmann thrombasthenia, Bernard-Soulier syndrome, and other disorders. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 5th ed. Philadelphia, PA; Lippincott Williams & Wilkins 2006: 987-1010
  • 20 Geddis A E, Kaushansky K. Inherited thrombocytopenias: toward a better molecular understanding of disorders of platelet production.  Curr Opin Pediatr. 2004;  16 15-22
  • 21 Peerschke E I, Zucker M B, Grant R A, Egan J J, Johnson M M. Correlation between fibrinogen binding to human platelets and platelet aggregability.  Blood. 1980;  55 841-847
  • 22 Nurden A, Fiore M, Pillois X, Nurden P. Genetic testing in the diagnostic evaluation of inherited platelet disorders.  Semin Thromb Hemost. 2009;  35 204-212
  • 23 Fritsma G A. Tests of platelet number and function. In: Corriveau DM, Fritsma GA Hemostasis and Thrombosis in the Clinical Laboratory. Philadelphia, PA; Lippincott 1988: 278-302
  • 24 Nieuwenhuis H K, Akkerman J W, Houdijk W PM, Sixma J J. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia.  Nature. 1985;  318 470-472
  • 25 Deckmyn H, Chew S L, Vermylen J. Lack of platelet response to collagen associated with an autoantibody against glycoprotein Ia: a novel cause of acquired qualitative platelet dysfunction.  Thromb Haemost. 1990;  64 74-79
  • 26 Cattaneo M. Inherited platelet-based bleeding disorders.  J Thromb Haemost. 2003;  1 1628-1636
  • 27 Gachet C. ADP receptors of platelets and their inhibition.  Thromb Haemost. 2001;  86 222-232
  • 28 Hirata T, Ushikubi F, Kakizuka A, Okuma M, Narumiya S. Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation.  J Clin Invest. 1996;  97 949-956
  • 29 Higuchi W, Fuse I, Hattori A, Aizawa Y. Mutations of the platelet thromboxane A2 (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity.  Thromb Haemost. 1999;  82 1528-1531
  • 30 Rao A K, Willis J, Kowalska M A, Wachtfogel Y T, Colman R W. Differential requirements for platelet aggregation and inhibition of adenylate cyclase by epinephrine. Studies of a familial platelet alpha 2-adrenergic receptor defect.  Blood. 1988;  71 494-501
  • 31 Meyer M, Kirchmaier C M, Schirmer A, Spangenberg P, Ströhl C, Breddin K. Acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIb-IIIa complex—1. Glycoprotein analysis.  Thromb Haemost. 1991;  65 491-496
  • 32 Campo G, Valgimigli M, Gemmati D. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study.  J Am Coll Cardiol. 2006;  48 2178-2185
  • 33 Nurden A T. Qualitative disorders of platelets and megakaryocytes.  J Thromb Haemost. 2005;  3 1773-1782
  • 34 Rao A K. Hereditary disorders of platelet secretion and signal transduction. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, PA; Lippincott Williams & Wilkins 2006: 961-974
  • 35 Rao A K, Koike K, Willis J et al.. Platelet secretion defect associated with impaired liberation of arachidonic acid and normal myosin light chain phosphorylation.  Blood. 1984;  64 914-921
  • 36 Pereira J, Quiroga T, Mezzano D. Laboratory assessment of familial, nonthrombocytopenic mucocutaneous bleeding: a definitive diagnosis is often not possible.  Semin Thromb Hemost. 2008;  34 654-662
  • 37 Poston R S, Gu J, White C et al.. Perioperative management of aspirin resistance after off-pump coronary artery bypass grafting: possible role for aprotinin.  Transfusion. 2008;  48(1, Suppl) 39S-46S
  • 38 Mascelli M A, Worley S, Veriabo N J et al.. Rapid assessment of platelet function with a modified whole-blood aggregometer in percutaneous transluminal coronary angioplasty patients receiving anti-GP IIb/IIIa therapy.  Circulation. 1997;  96 3860-3866
  • 39 Ivandic B T, Giannitsis E, Schlick P, Staritz P, Katus H A, Hohlfeld T. Determination of aspirin responsiveness by use of whole blood platelet aggregometry.  Clin Chem. 2007;  53 614-619
  • 40 Gu J, Prastein D, Pierson II R N et al.. Aspirin resistance: an underrecognized risk factor in early vein graft thrombosis after off-pump coronary artery bypass (OPCAB). Presented at: American Heart Association meeting November 7–10, 1994 Dallas, TX;
  • 41 Avram S, Lupu A, Angelescu S, Olteanu N, Mut-Popescu D. Abnormalities of platelet aggregation in chronic myeloproliferative disorders.  J Cell Mol Med. 2001;  5 79-87
  • 42 Zeidman A, Sokolover N, Fradin Z, Cohen A, Redlich O, Mittelman M. Platelet function and its clinical significance in the myelodysplastic syndromes.  Hematol J. 2004;  5 234-238
  • 43 Remold-O'Donnell E, Rosen F S, Kenney D M. Defects in Wiskott-Aldrich syndrome blood cells.  Blood. 1996;  87 2621-2631
  • 44 Drachman J G. Inherited thrombocytopenia: when a low platelet count does not mean ITP.  Blood. 2004;  103 390-398
  • 45 Nieuwenhuis H K, Akkerman J W, Sixma J J. Patients with a prolonged bleeding time and normal aggregation tests may have storage pool deficiency: studies on one hundred six patients.  Blood. 1987;  70 620-623
  • 46 Israels S J, McNicol A, Robertson C, Gerrard J M. Platelet storage pool deficiency: diagnosis in patients with prolonged bleeding times and normal platelet aggregation.  Br J Haematol. 1990;  75 118-121
  • 47 Manoharan A, Gemmell R, Brighton T, Dunkley S, Lopez K, Kyle P. Thrombosis and bleeding in myeloproliferative disorders: identification of at-risk patients with whole blood platelet aggregation studies.  Br J Haematol. 1999;  105 618-625
  • 48 Manoharan A, Brighton T, Gemmell R, Lopez K, Moran S, Kyle P. Platelet dysfunction in myelodysplastic syndromes: a clinicopathological study.  Int J Hematol. 2002;  76 272-278
  • 49 Manoharan A, Gemmell R, Hartwell T. Use of whole blood platelet lumi-aggregometry to optimize anti-platelet therapy in patients with chronic myeloproliferative disorders.  Am J Hematol. 2006;  81 676-683
  • 50 Löfvenberg E, Nilsson T K. Qualitative platelet defects in chronic myeloproliferative disorders: evidence for reduced ATP secretion.  Eur J Haematol. 1989;  43 435-440
  • 51 Girtovitis F I, Ntaios G, Papadopoulos A, Ioannidis G, Makris P E. Defective platelet aggregation in myelodysplastic syndromes.  Acta Haematol. 2007;  118 117-122
  • 52 Bevan D H. Cardiac bypass haemostasis: putting blood through the mill.  Br J Haematol. 1999;  104 208-219
  • 53 Despotis G J, Avidan M S, Hogue Jr C W. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.  Ann Thorac Surg. 2001;  72 S1821-S1831
  • 54 Whitlock R, Crowther M A, Ng H J. Bleeding in cardiac surgery: its prevention and treatment—an evidence-based review.  Crit Care Clin. 2005;  21 589-610
  • 55 Shaffer K E, Pearman D T, Galen R S, Carville D G. A rapid platelet function assay used to regulate platelet transfusion prophylaxis following cardiopulmonary bypass surgery.  J Extra Corpor Technol. 2004;  36 145-148
  • 56 Engelberger L, Faeh B, Berdat P A et al.. Impact of clopidogrel in coronary artery bypass grafting.  Eur J Cardiothorac Surg. 2004;  26 96-101
  • 57 Friend M, Vucenik I, Miller M. Research pointers: platelet responsiveness to aspirin in patients with hyperlipidaemia.  BMJ. 2003;  326 82-83
  • 58 Gresele P, Zoja C, Deckmyn H, Arnout J, Vermylen J, Verstraete M. Dipyridamole inhibits platelet aggregation in whole blood.  Thromb Haemost. 1983;  50 852-856
  • 59 Gresele P, Zoja C, Deckmyn H et al.. Dipyridamole inhibits platelet aggregation in whole blood.  Thromb Haemost. 1983;  50 852-856
  • 60 Nakamura T, Uchiyama S, Yamazaki M, Iwata M. Effects of dipyridamole and aspirin on shear-induced platelet aggregation in whole blood and platelet-rich plasma.  Cerebrovasc Dis. 2002;  14 234-238
  • 61 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
  • 62 de la Cruz J P, Camara S, Bellido I, Carrasco T, Sanchez de la Cuesta F. Platelet aggregation in human whole blood after chronic administration of aspirin.  Thromb Res. 1987;  46 133-140
  • 63 Sathiropas P, Marbet G A, Sahaphong S, Duckert F. Detection of small inhibitory effects of acetylsalicylic acid (ASA) by platelet impedance aggregometry in whole blood.  Thromb Res. 1988;  51 55-62
  • 64 McKee S A, Sane D C, Deliargyris E N. Aspirin resistance in cardiovascular disease: a review of prevalence, mechanisms, and clinical significance.  Thromb Haemost. 2002;  88 711-715
  • 65 Lordkipanidzé M, Pharand C, Schampaert E, Turgeon J, Palisaitis D A, Diodati J G. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease.  Eur Heart J. 2007;  28 1702-1708
  • 66 Dyszkiewicz-Korpanty A M, Kim A, Burner J D, Frenkel E P, Sarode R. Comparison of a rapid platelet function assay—Verify Now Aspirin—with whole blood impedance aggregometry for the detection of aspirin resistance.  Thromb Res. 2007;  120 485-488
  • 67 McGlasson D L, Fritsma G A. Comparison of four laboratory methods to assess aspirin sensitivity.  Blood Coagul Fibrinolysis. 2008;  19 120-123
  • 68 Nicholson N S, Panzer-Knodle S G, Haas N F et al.. Assessment of platelet function assays.  Am Heart J. 1998;  135(5 Pt 2 Suppl) S170-S178
  • 69 Santos M T, Valles J, Marcus A J et al.. Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment.  J Clin Invest. 1991;  87 571-580
  • 70 Valles J, Santos M T, Aznar J et al.. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.  Circulation. 1998;  97 350-355
  • 71 Patrignani P. Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease.  Thromb Res. 2003;  110 281-286
  • 72 Favaloro E J. Clinical utility of the PFA-100.  Semin Thromb Hemost. 2008;  34 709-733
  • 73 Michelson A D. Platelet function testing in cardiovascular diseases.  Circulation. 2004;  110 e489-e493
  • 74 Dyszkiewicz-Korpanty A, Olteanu H, Frenkel E P, Sarode R. Clopidogrel anti-platelet effect: an evaluation by optical aggregometry, impedance aggregometry, and the platelet function analyzer (PFA-100).  Platelets. 2007;  18 491-496
  • 75 Ivandic B T, Schlick P, Staritz P, Kurz K, Katus H A, Giannitsis E. Determination of clopidogrel resistance by whole blood platelet aggregometry and inhibitors of the P2Y12 receptor.  Clin Chem. 2006;  52 383-388
  • 76 Angiolillo D J, Fernández-Ortiz A, Bernardo E et al.. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability.  Eur Heart J. 2004;  25 1903-1910
  • 77 Gurbel P A, Bliden K P, Hayes K M, Yoho J A, Herzog W R, Tantry U S. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.  J Am Coll Cardiol. 2005;  45 1392-1396
  • 78 Siemens Healthcare Diagnostics Inc .Dade-Behring. Dade® PFA-100® Reagents. To aid in the detection of platelet dysfunction in citrated human whole blood. B4170 G20A U5734 (97) H/CS/R. Deerfield, IL; Siemens Healthcare Diagnostics Inc 2007: 5
  • 79 Hochholzer W, Trenk D, Frundi D, Neumann F J. Whole blood aggregometry for evaluation of the antiplatelet effects of clopidogrel.  Thromb Res. 2007;  119 285-291
  • 80 Sibbing D, Braun S, Jawansky S et al.. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment.  Thromb Haemost. 2008;  99 121-126
  • 81 Tóth O, Calatzis A, Penz S, Losonczy H, Siess W. Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood.  Thromb Haemost. 2006;  96 781-788
  • 82 Seyfert U T, Haubelt H, Vogt A, Hellstern P. Variables influencing Multiplate(TM) whole blood impedance platelet aggregometry and turbidimetric platelet aggregation in healthy individuals.  Platelets. 2007;  18 199-206
  • 83 Penz S M, Reininger A J, Toth O, Deckmyn H, Brandl R, Siess W. Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques.  Thromb Haemost. 2007;  97 435-443
  • 84 Mueller T, Dieplinger B, Poelz W, Calatzis A, Haltmayer M. Utility of whole blood impedance aggregometry for the assessment of clopidogrel action using the novel Multiplate analyzer—comparison with two flow cytometric methods.  Thromb Res. 2007;  121 249-258
  • 85 Mueller T, Dieplinger B, Poelz W, Haltmayer M. Utility of the PFA-100® instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease.  Clin Appl Thromb Hemost. 2008;  , September 19 (Epub ahead of print)
  • 86 Michelson A D, Cattaneo M, Eikelboom J W Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis et al. Aspirin resistance: position paper of the Working Group on Aspirin Resistance.  J Thromb Haemost. 2005;  3 1309-1311
  • 87 Frenkel E P, Mammen E F. Sticky platelet syndrome and thrombocythemia.  Hematol Oncol Clin North Am. 2003;  17 63-83
  • 88 Mühlfeld A S, Ketteler M, Schwamborn K et al.. Sticky platelet syndrome: an underrecognized cause of graft dysfunction and thromboembolic complications in renal transplant recipients.  Am J Transplant. 2007;  7 1865-1868
  • 89 Hackam D G, Eikelboom J W. Antithrombotic treatment for peripheral arterial disease.  Heart. 2007;  93 303-308
  • 90 Mackie I J, Bihari D, Machin S J. Increased platelet aggregability in native whole blood in the adult respiratory distress syndrome (ARDS).  Thromb Haemost. 1987;  58 1676 , [abstract]
  • 91 Jones R J, Delamothe A P, Curtis L D, Machin S J, Betteridge D J. Measurement of platelet aggregation in diabetics using the new electronic platelet aggregometer.  Diabet Med. 1985;  2 105-109
  • 92 Mandal S, Sarode R, Dash S, Dash R J. Hyperaggregation of platelets detected by whole blood platelet aggregometry in newly diagnosed noninsulin-dependent diabetes mellitus.  Am J Clin Pathol. 1993;  100 103-107
  • 93 Schinco P C, Fusaro A, Marranca R et al.. Paraproteinaemias and platelet aggregation: role of whole blood aggregometry.  Thromb Res. 1989;  55 267-277

David L McGlassonM.S. C.L.S./N.C.A. 

59 CSPG/SGVUL 2200 Berquist Drive

Building 4430, Lackland AFB, TX 78236-9908

Email: david.mcglasson@lackland.af.mil

    >