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Thromb Haemost 2011; 106(04): 675-682
DOI: 10.1160/TH11-06-0378
Platelets and Blood Cells
Schattauer GmbH

A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: Is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?

Jean Francois Castilloux
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Karen A. Moffat
2   Department of Medicine, McMaster University, McMaster University, Hamilton, Ontario, Canada
3   The Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada
,
Yang Liu
2   Department of Medicine, McMaster University, McMaster University, Hamilton, Ontario, Canada
,
Jodi Seecharan
3   The Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada
,
Menaka Pai
2   Department of Medicine, McMaster University, McMaster University, Hamilton, Ontario, Canada
3   The Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada
,
Catherine P. M. Hayward
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
2   Department of Medicine, McMaster University, McMaster University, Hamilton, Ontario, Canada
3   The Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations Financial support: The research was supported by the Hamilton Regional Laboratory Medicine Program and a Canada Research Chair from the Government of Canada (C.P.M.H.).
Further Information

Publication History

Received: 03 June 2011

Accepted after major revision: 15 June 2011

Publication Date:
29 November 2017 (online)

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Summary

Light transmission platelet aggregometry (LTA) is important to diagnose bleeding disorders. Experts recommend testing LTA with native (N) rather than platelet count adjusted (A) platelet-rich plasma (PRP), although it is unclear if this provides non-inferior, or superior, detection of bleeding disorders. Our goal was to determine if LTA with NPRP is noninferior to LTA with APRP for bleeding disorder assessments. A prospective cohort of patients, referred for bleeding disorder testing, and healthy controls, were evaluated by LTA using common agonists, NPRP and APRP (adjusted to 250 x 109 platelets/l). Recruitment continued until 40 controls and 40 patients with definite bleeding disorders were tested. Maximal aggregation (MA) data were assessed for the detection of abnormalities from bleeding disorders (all causes combined to limit bias), using sample-type specific reference intervals. Areas under receiver-operator curves (AUROC) were evaluated using pre-defined criteria (area differences: <0.15 for non-inferiority, >0 for superiority). Forty-four controls and 209 patients were evaluated. Chart reviews for 169 patients indicated 67 had bleeding disorders, 28 from inherited platelet secretion defects. Mean MA differences between NPRP and APRP were small for most agonists (ranges, controls: −3.3 to 5.8; patients: −3.0 to 13.7). With both samples, reduced MA with two or more agonists was associated with a bleeding disorder. AUROC differences between NPRP and APRP were small and indicated that NPRP were noninferior to APRP for detecting bleeding disorders by LTA, whereas APRP met superiority criteria. Our study validates using either NPRP or APRP for LTA assessments of bleeding disorders.

keywords

Clinical studies - platelet disorders - platelet pathology - inherited - acquired

 

  • References

  • 1 Hayward CP. Diagnostic evaluation of platelet function disorders. Blood Rev 2011; 25: 169-173.
    CrossrefPubMedSearch in Google Scholar
  • 2 Hayward CP, Pai M, Liu Y. et al. Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments. J Thromb Haemost 2009; 7: 676-684.
    CrossrefPubMedSearch in Google Scholar
  • 3 Quiroga T, Goycoolea M, Matus V. et al. Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays. Br J Haematol 2009; 147: 729-736.
    CrossrefPubMedSearch in Google Scholar
  • 4 Cattaneo M. Light transmission aggregometry and ATP release for the diagnostic assessment of platelet function. Semin Thromb Hemost 2009; 35: 158-167.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Cattaneo M, Hayward CP, Moffat KA. et al. 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: 1029.
    CrossrefPubMedSearch in Google Scholar
  • 6 Christie DJ, Avari T, Carrington LR. et al. Clinical and Laboratory Standards Institute (CLSI). Platelet function testing by aggregometry; approved guideline. CLSI document H58-A (ISBN 1–56238–683–2). Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2008. 28(31): available at: http://www.clsi.org Assessed May 31, 2011.
    Search in Google Scholar
  • 7 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: 955-963.
    CrossrefPubMedSearch in Google Scholar
  • 8 Pai M, Hayward CP. Diagnostic assessment of platelet disorders: what are the challenges to standardization?. Semin Thromb Hemost 2009; 35: 131-138.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Cattaneo M, Lecchi A, Zighetti ML. et al. Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count. Haematologica 2007; 92: 694-697.
    CrossrefPubMedSearch in Google Scholar
  • 10 Mani H, Luxembourg B, Klaffling C. et al. Use of native or platelet count adjusted platelet rich plasma for platelet aggregation measurements. J Clin Pathol 2005; 58: 747-750.
    CrossrefPubMedSearch in Google Scholar
  • 11 Linnemann B, Schwonberg J, Mani H. et al. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary. J Thromb Haemost 2008; 6: 677-683.
    CrossrefPubMedSearch in Google Scholar
  • 12 Favaloro EJ, Mohammed S. Platelet function testing: auditing local practice and broader implications. Clin Lab Sci 2010; 23: 21-31.
    PubMedSearch in Google Scholar
  • 13 van der Stelt CA, van Werkum JW, Seesing TH. et al. To adjust or not to adjust the platelet count in light transmission aggregometry in patients receiving dual aspirin/clopidogrel treatment. Platelets 2007; 18: 550-553.
    CrossrefPubMedSearch in Google Scholar
  • 14 Hayward CP, Moffat KA, Pai M. et al. An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts. Thromb Haemost 2008; 100: 134-145.
    PubMedSearch in Google Scholar
  • 15 Pai M, Wang G, Moffat KA. et al. Diagnostic utility of a lumiaggregometer adenosine triphosphate release assay for the assessment of platelet function disorders. Am J Clin Pathol. 2011 in press.
    PubMedSearch in Google Scholar
  • 16 Paterson AD, Rommens JM, Bharaj B. et al. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood 11-2-2010 115: 1264-1266.
    PubMed
  • 17 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-845.
    CrossrefPubMedSearch in Google Scholar
  • 18 Piaggio G, Elbourne DR, Altman DG. et al. Reporting of non-inferiority and equivalence randomized trials: an extension of the CONSORT statement. J Am Med Assoc 2006; 295: 1152-1160.
    CrossrefPubMedSearch in Google Scholar
  • 19 Diamandis M, Veljkovic DK, Maurer-Spurej E. et al. Quebec platelet disorder: features, pathogenesis and treatment. Blood Coagul Fibrinolysis 2008; 19: 109-119.
    CrossrefPubMedSearch in Google Scholar
  • 20 Li CR, Liao CT, Liu JP. A non-inferiority test for diagnostic accuracy based on the paired partial areas under ROC curves. Stat Med 2008; 27: 1762-1776.
    CrossrefPubMedSearch in Google Scholar
  • 21 Mezzano D, Quiroga T, Pereira J. The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays. Semin Thromb Hemost 2009; 35: 242-254.
    Thieme ConnectPubMedSearch in Google Scholar