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A blinded study of bone marrow examinations in patients with primary immune thrombocytopenia
Vishwanath K Mahabir1, Catherine Ross, Snezana Popovic
1Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
Insights
Bone marrow examinations are unreliable for diagnosing immune thrombocytopenia (ITP). This study found poor inter-rater reliability and low sensitivity, suggesting they are not useful for typical ITP cases.
Area of Science:
- Hematology
- Pathology
- Medical Diagnostics
Background:
- The diagnostic utility of bone marrow examinations in primary immune thrombocytopenia (ITP) remains unclear.
- ITP is an autoimmune disorder characterized by low platelet counts.
Purpose of the Study:
- To assess the inter-rater reliability of bone marrow examinations in ITP diagnosis.
- To identify distinctive morphological features in ITP bone marrows under controlled conditions.
Main Methods:
- Histological slides from 32 severe primary ITP patients and 51 controls were reviewed by three blinded hematopathologists.
- Raters evaluated megakaryocyte number, morphology, and distribution to identify ITP bone marrows.
Main Results:
- Inter-rater agreement for ITP classification was poor (kappa = 0.30).
- Raters struggled to differentiate ITP bone marrows from controls, with overall sensitivity of 24% and specificity of 90%.
- An increased megakaryocyte count, though uncommon, was more frequent in ITP patients.
Conclusions:
- Bone marrow examinations are methodologically unreliable and often non-diagnostic for typical ITP.
- These examinations are generally not useful for patients with typical ITP.
- Rare ITP subsets may exhibit unique features like increased megakaryocytes.
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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