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

Immune thrombocytopenia (ITP) is a common autoimmune disorder characterized by low platelet counts that can lead to bleeding (1). ITP patients typically have no other physical or laboratory findings to confirm the diagnosis; thus, ITP remains a diagnosis of exclusion. Measurements of platelet turnover and antiplatelet antibodies have been examined in ITP patients; however, platelet turnover studies are not easily applied in practice and current platelet autoantibody testing is insensitive (2, 3). The recent introduction of thrombopoietin (TPO) receptor agonists as an effective treatment for ITP has reaffirmed that ITP may be caused by an impairment in platelet production and has refocused attention on abnormalities of bone marrow megakaryocytes (4). Bone marrow examinations in ITP have been investigated in studies dating back several decades. Some investigators have found megakaryocyte numbers to be increased (5–7), while others have found them to be normal (8). Similarly, abnormal megakaryocyte morphology including diminished granularity and decreased nuclear ploidy among other findings were observed by some investigators (9, 10) but not others (11, 12). These discrepancies may have arisen because early studies lacked appropriate methodological tools or as a reflection of the subjective nature of bone marrow reporting. Overall, investigators have reached differing conclusions as to whether bone marrow morphology displays unique features in ITP, and the value of bone marrow examinations in ITP in general. Recent guidelines recommend against bone marrow examinations in typical ITP patients (13); however, the evidence in support of this recommendation was weak. To definitively address the usefulness of bone marrow examinations in patients with ITP, we determined the inter-rater reliability and accuracy of this test based on blinded, independent review of bone marrow specimens by three experienced hematopathologists. The objectives were to determine the agreement between raters and to describe morphological features unique to ITP patients. This study has implications for clinical practice and may shed light on ITP pathogenesis.