Absolute Immature Platelet Count As an Accessible Diagnostic Tool for Aplastic Anemia Vs. Immune Thrombocytopenia

Introduction

When evaluating thrombocytopenia, it is crucial to accurately distinguish between megakaryocyte hypoplasia resulting from a bone marrow failure disorder such as in aplastic anemia (AA) and platelet destruction due to immune thrombocytopenia (ITP). This accurate differentiation is essential for making prompt treatment decisions and averting potential complications from thrombocytopenia and treatment complications, notably major bleeding and infections, respectively. Hee-Jin Kim et al. showed the utility of immature platelet fraction (IPF%) in differentiating between ITP and AA, albeit with limited sensitivity of 54.0% (Kim et al., 2010). IPF% can be influenced by platelet transfusions (Bat et al., 2013). Megakaryocyte production may also be suppressed among ITP patients, potentially complicating the distinction of ITP and AA, particularly in cases where thrombocytopenia is the predominant feature, likely related to antiplatelet autoantibodies (McMillan et al., 2004). This underscores the urgent requirement for a more refined biomarker in the clinical realm to aid with improving diagnostic accuracy. We hypothesize that absolute immature platelet number (AIPN) can be a more sensitive and specific test to differentiate AA and ITP.

Methods

Our study cohort encompassed a diverse array of participants with ITP (n=32) and those with AA (n=15) from 2015-2023 seen at the University of Texas Southwestern Medical Center. We retrospectively analyzed medical records of patients at our institution with diagnosis of AA and ITP to determine IPF% collected at the time of the diagnosis and before the onset of ITP treatment as well as while on treatment, respectively. The AIPN was calculated by multiplying the IPF by the circulating platelet count and dividing by 100.

This study was approved by the Institutional Review Board (IRB) at University of Texas Southwestern with reference number STU-2021-1114.

Results

We compared AIPN values of 15 AA subjects (M = 0.74, SD = 0.755) to the 48 ITP subjects (M = 12.2, SD = 13.09), and found that the AA cohort consists of significantly lower AIPN values by t-test (t-value=3.4, p<0.05). Our analysis identified an optimal threshold at which AA was classified as AIPN<=2.1 x109/L and ITP was classified as AIPN>2.1 x109/L, with AUC of 0.91, accuracy of 94%, sensitivity of 93% (correct prediction of AA), and specificity of 94% (correct prediction of ITP).

We additionally compared IPF% values of 15 AA subjects (M = 4.2, SD = 9.32) to the 48 ITP subjects (M = 20.2, SD = 230.13), and found that the AA cohort consists of significantly lower IPF% values by t-test (t-value=4.1, p<0.05). However, from various IPF% thresholds ranging from 2.1 to 12.6%, no IPF% threshold results in both sensitivity and specificity over 70%. Therefore, we infer that AIPN provides a more accurate indicator of AA versus ITP.

Conclusions

Markedly elevated thrombopoietin (TPO) levels are specifically linked to thrombocytopenia caused by megakaryocyte hypoplasia due to bone marrow failure, as opposed to situations characterized by platelet destruction (Bat et al., 2013; Emmons et al., 1996). However, it's essential to note that measuring TPO levels is not currently a standard practice, often not readily available in local labs, and is primarily reserved for research purposes. In clinical scenarios, AA patients may be incorrectly diagnosed and treated for ITP. This misclassification can lead to delays in administering the appropriate treatment for AA, worsening the overall prognosis (Nakao, 2016). While our cohort is small and the results need to be confirmed in a larger study, our findings underscore the importance of AIPN in guiding clinicians to reliably differentiate between AA and ITP with high accuracy. The simplicity, feasibility, and accessibility of AIPN testing make it a valuable and reliable biomarker for clinical use. It serves as a tool in facilitating prompt and accurate diagnoses, thereby enhancing the overall management of patients with aplastic anemia.