A blinded study of bone marrow examinations in patients with primary immune thrombocytopenia

Authors

  • Vishwanath K. Mahabir,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Catherine Ross,

    1. Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Snezana Popovic,

    1. Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Mona Lisa Sur,

    1. Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Jacqueline Bourgeois,

    1. Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Wendy Lim,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • James N. George,

    1. Department of Biostatistics and Epidemiology, College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
    2. Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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  • Grace Wang,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Richard J. Cook,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
    2. Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
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  • Lisa J. Toltl,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Ishac Nazi,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • John G. Kelton,

    1. Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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  • Donald M. Arnold

    Corresponding author
    1. Canadian Blood Services, Hamilton, ON, Canada
    • Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
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Correspondence Donald M. Arnold, MD, MSc, FRCP(C), HSC 3V-50, 1280 Main Street West, Hamilton, ON, Canada. Tel: 905 521 2100 ext. 76305; Fax: 905 521 4971; e-mail: arnold@mcmaster.ca

Abstract

Objective

The role of bone marrow examinations in patients with primary immune thrombocytopenia (ITP) is uncertain. The objectives of this study were to determine the inter-rater reliability of bone marrow examinations and to identify distinguishing morphological features of ITP bone marrows under controlled conditions.

Methods

Histological slides of bone marrow biopsy specimens and aspirates from 32 adult patients with severe primary ITP who had failed a median of two treatments, and 51 non-thrombocytopenic controls were retrieved from hospital archives. Slides were arranged in random order in a slide box and coded. Blinded to the diagnosis and platelet counts, three independent hematopathologists were asked to identify the ITP bone marrows and to evaluate megakaryocyte number, morphology, and distribution.

Results

Overall chance-corrected agreement on ITP classification among the three raters was poor [kappa (κ) = 0.30; 95% confidence interval 0.22–0.38]. Raters were generally unable to correctly identify the ITP bone marrows from controls. Increased number of megakaryocytes, while an uncommon finding, was more frequent among ITP patients compared with controls (6/32, 18.8%; vs. 2/51, 3.9%; P = 0.05), and abnormal megakaryocyte morphology often led individual raters to reach a diagnosis of ITP. Overall sensitivity and specificity of bone marrow examinations were 24% and 90%, respectively.

Conclusions

This study confirms methodologically that bone marrow examinations are unreliable and frequently non-diagnostic in ITP. Thus, they are not useful for patients with typical disease. Rare subsets of patients with severe ITP demonstrated unique features such as increased number of megakaryocytes.

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