Diagnostic Assessment of Platelet Disorders: What Are the Challenges to Standardization?

ABSTRACT

The platelet disorders are a group of heterogeneous, congenital and acquired bleeding disorders associated with impaired platelet function. There is a growing interest in standardizing the assessment of these disorders, but this is challenged by their heterogeneity, the absence of widely accepted diagnostic criteria, and inconsistency in laboratory testing practices for platelet disorders. Symptoms commonly associated with platelet disorders include rapid-onset bleeding with hemostatic challenges, peripartum bleeding, menorrhagia, epistaxis, gingival bleeding, and increased bruising. Attempts have been made to standardize the assessment of these symptoms, using clinical tools and bleeding scores. However, there are currently no standardized tools available with proven utility for the assessment of platelet disorders, apart from a tool specifically designed to assess Quebec platelet disorder. There have been several efforts to improve and standardize the laboratory assessment of platelet disorders. These efforts include guidelines from the International Society on Thrombosis and Haemostasis and the Clinical and Laboratory Standards Institute. Recent research indicates that the application of standardized laboratory tests for the assessment of platelet disorders in individuals referred for bleeding problems has valuable diagnostic utility. This has provided further incentive to standardize clinical and laboratory approaches to improve the diagnostic evaluation of platelet disorders worldwide.

KEYWORDS

Platelet disorders - bleeding scores - platelet function tests - laboratory diagnosis

REFERENCES

• 1 Watson H G, Greaves M. Can we predict bleeding?.  Semin Thromb Hemost. 2008;  34 97-103
• 2 Rodeghiero F, Kadir R A, Tosetto A, James P D. Relevance of quantitative assessment of bleeding in haemorrhagic disorders.  Haemophilia. 2008;  14(Suppl 3) 68-75
• 3 Tosetto A, Castaman G, Rodeghiero F. Bleeding scores in inherited bleeding disorders: clinical or research tools?.  Haemophilia. 2008;  14 415-422
• 4 Kouides P A. Bleeding symptom assessment and hemostasis evaluation of menorrhagia.  Curr Opin Hematol. 2008;  15 465-472
• 5 Favaloro E. Internal quality control and external quality assurance of platelet function tests.  Semin Thromb Hemost. 2009;  35 139-149
• 6 Harrison P, Mumford A. Screening tests of platelet function: update on their appropriate uses for diagnostic testing.  Semin Thromb Hemost. 2009;  35 150-157
• 7 Israels S J. Diagnostic evaluation of platelet function disorders in neonates and children: an update.  Semin Thromb Hemost. 2009;  35 181-188
• 8 Althaus K, Greinacher A. MYH9-related platelet disorders.  Semin Thromb Hemost. 2009;  35 189-203
• 9 Cattaneo M. Light transmission aggregometry and ATP release for the diagnostic assessment of platelet function.  Semin Thromb Hemost. 2009;  35 158-167
• 10 McGlasson D, Fritsma G. Whole blood platelet aggregometry and platelet function testing.  Semin Thromb Hemost. 2009;  35 168-180
• 11 Nurden A T, Fiore M, Pillois X, Nurden P. Genetic testing in the diagnostic evaluation of inherited platelet disorders.  Semin Thromb Hemost. 2009;  35 204-212
• 12 Weiss H J. Impaired platelet procoagulant mechanisms in patients with bleeding disorders.  Semin Thromb Hemost. 2009;  35 233-241
• 13 Miller J. Glycoprotein analysis for the diagnostic evaluation of platelet disorders.  Semin Thromb Hemost. 2009;  35 224-232
• 14 Clauser S, Cramer-Borde E M. Role of platelet electron microscopy in the diagnosis of platelet disorders.  Semin Thromb Hemost. 2009;  35 213-223
• 15 Mezzano D, Quiroga T, Pereira J. The level of laboratory testing required for diagnosis or exclusion of a platelet function defect using platelet aggregation and secretion assays.  Semin Thromb Hemost. 2009;  35 242-254
• 16 Hayward C P, Rao A K, Cattaneo M. Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment.  Haemophilia. 2006;  12(Suppl 3) 128-136
• 17 McKay H, Derome F, Haq M A et al.. Bleeding risks associated with inheritance of the Quebec platelet disorder.  Blood. 2004;  104 159-165
• 18 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
• 19 Hayward C P, 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;  , January 7 (Epub ahead of print)
• 20 James A H, Ragni M V, Picozzi V J. Bleeding disorders in premenopausal women: (another) public health crisis for hematology?.  Hematology Am Soc Hematol Educ Program. 2006;  474-485
• 21 Philipp C S, Dilley A, Miller C H et al.. Platelet functional defects in women with unexplained menorrhagia.  J Thromb Haemost. 2003;  1 477-484
• 22 Nurden P, Nurden A T. Congenital disorders associated with platelet dysfunctions.  Thromb Haemost. 2008;  99 253-263
• 23 Weinrieb R M, Auriacombe M, Lynch K G, Lewis J D. Selective serotonin re-uptake inhibitors and the risk of bleeding.  Expert Opin Drug Saf. 2005;  4 337-344
• 24 Gunay-Aygun M, Huizing M, Gahl W A. Molecular defects that affect platelet dense granules.  Semin Thromb Hemost. 2004;  30 537-547
• 25 Kaplan J, De Domenico I, Ward D M. Chediak-Higashi syndrome.  Curr Opin Hematol. 2008;  15 22-29
• 26 Karim M A, Suzuki K, Fukai K et al.. Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome.  Am J Med Genet. 2002;  108 16-22
• 27 Mehdizadeh M, Zamani G. Griscelli syndrome: a case report.  Pediatr Hematol Oncol. 2007;  24 525-529
• 28 Seri M, Cusano R, Gangarossa S et al.. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium.  Nat Genet. 2000;  26 103-105
• 29 Greenhalgh K L, Howell R T, Bottani A et al.. Thrombocytopenia-absent radius syndrome: a clinical genetic study.  J Med Genet. 2002;  39 876-881
• 30 Miller C H, Graham J B, Goldin L R, Elston R C. Genetics of classic von Willebrand's disease. II. Optimal assignment of the heterozygous genotype (diagnosis) by discriminant analysis.  Blood. 1979;  54 137-145
• 31 Wahlberg T, Blomback M, Hall P, Axelsson G. Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions.  Methods Inf Med. 1980;  19 194-200
• 32 Nosek-Cenkowska B, Cheang M S, Pizzi N J, Israels E D, Gerrard J M. Bleeding/bruising symptomatology in children with and without bleeding disorders.  Thromb Haemost. 1991;  65 237-241
• 33 Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count.  Haematologica. 2005;  90 829-832
• 34 Diamandis M, Veljkovic D K, Maurer-Spurej E, Rivard G E, Hayward C P. Quebec platelet disorder: features, pathogenesis and treatment.  Blood Coagul Fibrinolysis. 2008;  19 109-119
• 35 Diamandis M, Paterson A D, Rommens J M et al.. Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes.  Blood. 2009;  113 1543-1546
• 36 Veljkovic D K, Rivard G E, Diamandis M, Blavignac J, Cramer-Borde E M, Hayward C P. Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation.  Blood. 2009;  113 1535-1542
• 37 Sramek A, Eikenboom J C, Briet E, Vandenbroucke J P, Rosendaal F R. Usefulness of patient interview in bleeding disorders.  Arch Intern Med. 1995;  155 1409-1415
• 38 Tosetto A, Rodeghiero F, Castaman G et al.. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD).  J Thromb Haemost. 2006;  4 766-773
• 39 Hedlund-Treutiger I, Revel-Vilk S, Blanchette V S, Curtin J A, Lillicrap D, Rand M L. Reliability and reproducibility of classification of children as “bleeders” versus “non-bleeders” using a questionnaire for significant mucocutaneous bleeding.  J Pediatr Hematol Oncol. 2004;  26 488-491
• 40 Castaman G, Rodeghiero F, Tosetto A et al.. Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study.  J Thromb Haemost. 2006;  4 2164-2169
• 41 Schulman S, Eelde A, Holmstrom M, Stahlberg G, Odeberg J, Blomback M. Validation of a composite score for clinical severity of hemophilia.  J Thromb Haemost. 2008;  6 1113-1121
• 42 Sharathkumar A, Hardesty B, Greist A et al.. Variability in bleeding phenotype in Amish carriers of haemophilia B with the 31008 C→T mutation.  Haemophilia. 2009;  15 91-100
• 43 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;  92 357-365
• 44 Hayward C P, Eikelboom J. Platelet function testing: quality assurance.  Semin Thromb Hemost. 2007;  33 273-282
• 45 Hayward C P, Harrison P, Cattaneo M, Ortel T L, Rao A K. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function.  J Thromb Haemost. 2006;  4 312-319
• 46 Michelson A D, Cattaneo M, Eikelboom J W et al.. Aspirin resistance: position paper of the Working Group on Aspirin Resistance.  J Thromb Haemost. 2005;  3 1309-1311
• 47 Christie D J, Avari T, Carrington L R et al.. Platelet Function Testing by Aggregometry; Approved Guideline. Wayne, PA; Clinical and Laboratory Standards Institute 2008; 28(31):1–45 http://Available at: www.clsi.org Accessed March 30, 2009
• 48 Guidelines on platelet function testing. The British Society for Haematology BCSH Haemostasis and Thrombosis Task Force.  J Clin Pathol. 1988;  41 1322-1330
• 49 Hayward C P, Moffat K A, Spitzer E et al.. Results of an external proficiency testing exercise on platelet dense granule deficiency testing by whole mount electron microscopy.  Am J Clin Pathol. 2009;  131 671-675
• 50 Hayward C P, Moffat K A, 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
• 51 Moffat K A, Ledford-Kraemer M R, Nichols W L, Hayward C P. 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
• 52 Jennings I, Woods T A, Kitchen S, Walker I D. Platelet function testing: practice among UK National External Quality Assessment Scheme for Blood Coagulation participants, 2006.  J Clin Pathol. 2008;  61 950-954
• 53 Duncan E M, Bonar R, Rodgers S E, Favaloro E J, Marsden K. Methodology and outcomes of platelet aggregation testing in Australia, New Zealand and the Asia-Pacific region: results of a survey from the Royal College of Pathologists of Australasia Haematology Quality Assurance Program.  Int J Lab Hematol. 2008;  , March 21 (Epub ahead of print)