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CC BY 4.0 · TH Open 2020; 04(04): e427-e436
DOI: 10.1055/s-0040-1721502
Original Article

Utility of the Platelet Function Analyzer in Patients with Suspected Platelet Function Disorders: Diagnostic Accuracy Study

Jonas Kaufmann
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland
,
Marcel Adler
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland
2   Division of Hematology and Central Hematology Laboratory, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
,
Lorenzo Alberio
2   Division of Hematology and Central Hematology Laboratory, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
3   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
,
Michael Nagler 
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland
4   University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Abstract

Introduction The platelet function analyzer (PFA) is widely used as a screening tool for bleeding disorders in various settings. The diagnostic performance regarding platelet function disorders (PFDs), which are among the most common inherited bleeding disorders, is however still elusive. We aimed to assess the diagnostic value of PFA for PFD in clinical practice.

Methods Comprehensive clinical and laboratory data of all consecutive patients referred to a specialized outpatient between January 2012 and March 2017 with a suspected bleeding disorder were prospectively recorded. The diagnostic work-up was performed according to a prespecified protocol following current guidelines and platelet function was tested using light transmission aggregometry as well as flow cytometry.

Results Five hundred and fifty-five patients were included (median age 43.7 years; interquartile range [IQR] 29.3, 61.7; 66.9% female). Possible PFD was diagnosed in 64 patients (11.5%) and confirmed PFD in 54 patients (9.7%). In patients with confirmed PFD, median closure times were 107 seconds (ADP or adenosine diphosphate; IQR 89, 130) and 169 seconds (EPI; IQR 121, 211). In patients without bleeding disorders, PFA closure times were 96 seconds (ADP; IQR 83, 109) and 137 seconds (EPI; IQR 116, 158). The sensitivity was 19.5% in case of PFA ADP (95%CI 12.6, 30.0; specificity 86.4%; 95% CI 82.4, 89.8), and 44.3% in case of PFA EPI (95% CI 34.9, 53.9; specificity 75.6%; 95% CI 70.8, 79.9).

Conclusion The diagnostic performance of PFA for PFD was moderate to poor. Our results do not support the utilization of PFA for screening of PFD in clinical practice.

Keywords

platelet function analyzer - Glanzmann thrombasthenia - platelet rich plasma - Bernard-Soulier syndrome - predictive value

Authors' Contributions

J.K. and M.A. collected the data, participated in data-analysis, and wrote the manuscript. L.A. implemented the work-up of patients, reviewed the data-analysis, and intellectually reviewed the manuscript. M.N. designed the study, conducted the analysis, and wrote the manuscript. All authors approved the final version of the manuscript.




Publication History

Received: 14 July 2020

Accepted: 28 October 2020

Article published online:
22 December 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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  • References

  • 1 Podda G, Femia EA, Pugliano M, Cattaneo M. Congenital defects of platelet function. Platelets 2012; 23 (07) 552-563
    CrossrefPubMedGoogle Scholar
  • 2 Nurden AT, Freson K, Seligsohn U. Inherited platelet disorders. Haemophilia 2012; 18 (Suppl. 04) 154-160
    CrossrefPubMedGoogle Scholar
  • 3 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 (09) 1562-1569
    CrossrefPubMedGoogle Scholar
  • 4 Matthews DC. Inherited disorders of platelet function. Pediatr Clin North Am 2013; 60 (06) 1475-1488
    CrossrefPubMedGoogle Scholar
  • 5 Gresele P. Subcommittee on Platelet Physiology of the International Society on Thrombosis and Hemostasis. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost 2015; 13 (02) 314-322
    CrossrefPubMedGoogle Scholar
  • 6 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 (01) 30-44
    CrossrefPubMedGoogle Scholar
  • 7 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; (e-pub ahead of print) DOI: 10.1111/jth.12231.
    CrossrefPubMedGoogle Scholar
  • 8 Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost 2008; 34 (08) 709-733
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Favaloro EJ. Clinical utility of closure times using the platelet function analyzer-100/200. Am J Hematol 2017; 92 (04) 398-404
    CrossrefPubMedGoogle Scholar
  • 10 Mammen EF, Comp PC, Gosselin R. et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24 (02) 195-202
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 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 (03) 195-204
    CrossrefPubMedGoogle Scholar
  • 12 Koscielny J, von Tempelhoff GF, Ziemer S. et al. A practical concept for preoperative management of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10 (02) 155-166
    CrossrefPubMedGoogle Scholar
  • 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 (04) 1325-1331
    CrossrefPubMedGoogle Scholar
  • 14 Favaloro EJ, Pasalic L, Curnow J. Monitoring therapy during treatment of von Willebrand disease. Semin Thromb Hemost 2017; 43 (03) 338-354
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Kilanowska J, Favaloro EJ, Lippi G. Aspirin ‘responsiveness’, ‘nonresponsiveness’ or ‘resistance’: a putative role for von Willebrand factor?. Blood Coagul Fibrinolysis 2008; 19 (08) 823-824
    CrossrefPubMedGoogle Scholar
  • 16 Adler M, Kaufmann J, Alberio L, Nagler M. Diagnostic utility of the ISTH bleeding assessment tool in patients with suspected platelet function disorders. J Thromb Haemost 2019; 17 (07) 1104-1112
    CrossrefPubMedGoogle Scholar
  • 17 Tosetto A, Castaman G, Plug I, Rodeghiero F, Eikenboom J. Prospective evaluation of the clinical utility of quantitative bleeding severity assessment in patients referred for hemostatic evaluation. J Thromb Haemost 2011; 9 (06) 1143-1148
    CrossrefPubMedGoogle Scholar
  • 18 de Moerloose P, Levrat E, Fontana P, Boehlen F. Diagnosis of mild bleeding disorders. Swiss Med Wkly 2009; 139 (23-24): 327-332
    PubMedGoogle Scholar
  • 19 Boender J, Kruip MJ, Leebeek FW. A diagnostic approach to mild bleeding disorders. J Thromb Haemost 2016; 14 (08) 1507-1516
    CrossrefPubMedGoogle Scholar
  • 20 Greaves M, Watson HG. Approach to the diagnosis and management of mild bleeding disorders. J Thromb Haemost 2007; 5 (Suppl. 01) 167-174
    CrossrefPubMedGoogle Scholar
  • 21 Daskalakis M, Colucci G, Keller P. et al. Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis. Cytometry B Clin Cytom 2014; 86 (Suppl. 06) 397-409
    CrossrefPubMedGoogle Scholar
  • 22 Rodeghiero F, Tosetto A, Abshire T. et al; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
    CrossrefPubMedGoogle Scholar
  • 23 CLSI, Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays, Approved Guideline—5th ed., CLSI document H21-A5. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
  • 24 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 (06) 955-963
    CrossrefPubMedGoogle Scholar
  • 25 Thommen D, Sulzer I, Buhrfeind E, Naef R, Furlan M, Lämmle B. Measurement of bleeding time and study of thrombocyte aggregation. Standardization of methods, normal values and results in patients with suspected hemorrhagic diathesis. Schweiz Med Wochenschr 1988; 118 (43) 1559-1567
    PubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Knöfler R, Eberl W, Schulze H. et al. Diagnosis of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.). Hamostaseologie 2014; 34 (03) 201-212
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Kottke-Marchant K, Corcoran G. The laboratory diagnosis of platelet disorders. Arch Pathol Lab Med 2002; 126 (02) 133-146
    CrossrefPubMedGoogle Scholar
  • 29 Bidlingmaier C, Grote V, Budde U, Olivieri M, Kurnik K. Prospective evaluation of a pediatric bleeding questionnaire and the ISTH bleeding assessment tool in children and parents in routine clinical practice. J Thromb Haemost 2012; 10 (07) 1335-1341
    CrossrefPubMedGoogle Scholar
  • 30 Laffan M, Brown SA, Collins PW. et al. The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization. Haemophilia 2004; 10 (03) 199-217
    CrossrefPubMedGoogle Scholar
  • 31 Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101 (06) 2089-2093
    CrossrefPubMedGoogle Scholar
  • 32 Sadler JE, Budde U, Eikenboom JC. et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4 (10) 2103-2114
    CrossrefPubMedGoogle Scholar
  • 33 Sadler JE, Rodeghiero F. ISTH SSC Subcommittee on von Willebrand Factor. Provisional criteria for the diagnosis of VWD type 1. J Thromb Haemost 2005; 3 (04) 775-777
    CrossrefPubMedGoogle Scholar
  • 34 Quiroga T, Goycoolea M, Belmont S. et al. Quantitative impact of using different criteria for the laboratory diagnosis of type 1 von Willebrand disease. J Thromb Haemost 2014; 12 (08) 1238-1243
    CrossrefPubMedGoogle Scholar
  • 35 Leebeek FW, Eikenboom JC. Von Willebrand's disease. N Engl J Med 2016; 375 (21) 2067-2080
    CrossrefPubMedGoogle Scholar
  • 36 White II GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J. Factor VIII and Factor IX Subcommittee. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001; 85 (03) 560
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Quiroga T, Mezzano D. Is my patient a bleeder? A diagnostic framework for mild bleeding disorders. Hematology (Am Soc Hematol Educ Program) 2012; 2012: 466-474
    CrossrefPubMedGoogle Scholar
  • 38 Elbatarny M, Mollah S, Grabell J. et al; Zimmerman Program Investigators. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia 2014; 20 (06) 831-835
    CrossrefPubMedGoogle Scholar
  • 39 Quiroga T, Goycoolea M, Panes O. et al. High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. Haematologica 2007; 92 (03) 357-365
    CrossrefPubMedGoogle Scholar
  • 40 Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti ML. Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion. Thromb Res 1999; 96 (03) 213-217
    CrossrefPubMedGoogle Scholar
  • 41 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 (04) 225-232
    CrossrefPubMedGoogle Scholar
  • 42 Buyukasik Y, Karakus S, Goker H. et al. Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease. Blood Coagul Fibrinolysis 2002; 13 (04) 349-353
    CrossrefPubMedGoogle Scholar
  • 43 Quiroga T, Goycoolea M, Muñoz 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 (06) 892-898
    CrossrefPubMedGoogle Scholar
  • 44 Moenen FCJI, Vries MJA, Nelemans PJ. et al. Screening for platelet function disorders with Multiplate and platelet function analyzer. Platelets 2019; 30 (01) 81-87
    CrossrefPubMedGoogle Scholar
  • 45 Gresele P, Bury L, Mezzasoma AM, Falcinelli E. Platelet function assays in diagnosis: an update. Expert Rev Hematol 2019; 12 (01) 29-46
    CrossrefPubMedGoogle Scholar