A large, single-center analysis of pediatric patients with either acquired aplastic anemia (aAA) or immune thrombocytopenia (ITP) has compared the serum thrombopoietin (TPO) levels in these patients. The results, from more than 400 patients, show that serum TPO levels were elevated in those pediatric patients diagnosed with aAA compared to ITP. In patients with aAA, serum TPO levels were highest in very severe AA. In patients with ITP, serum TPO levels were lower in those patients with chronic ITP compared to newly diagnosed or persistent ITP. These results of the study done at Beijing Children’s Hospital were published in the Journal of Pediatric Hematology/Oncology.
“When a pediatric patient presents with thrombocytopenia, it can be challenging to determine if the thrombocytopenia is due to a production problem, which occurs with aAA, versus a destruction problem, as occurs with ITP. There are currently no good biologic markers with adequate sensitivity and specificity to distinguish between these causes. Assessing serum TPO levels as a potential biomarker to distinguish between diseases would be beneficial,” said Nicola Wright, MD, a clinical associate professor of pediatric hematology/immunology at the Cumming School of Medicine at the University of Calgary in Canada who was not involved in the current study.
TPO is a factor that stimulates blood cell production and plays a crucial role in regulating platelet production and the development of megakaryocytes. Hui Chen, PhD, of the Beijing Key Laboratory of Pediatric Hematology/Oncology, and colleagues analyzed the endogenous plasma concentration of TPO and platelet count at the time of TPO measurement in pediatric patients with ITP and aAA, diagnosed between March 2021 and August 2022, to better understand the relationship between platelet counts and serum TPO levels specifically. Patients with aAA were under age 18, were either newly diagnosed or previously untreated with a TPO or TPO receptor agonist, and did not have an inherited bone marrow failure syndrome.
One hundred and sixty-six pediatric patients with aAA were enrolled and were an average age of 8 years old (range = 1-16 years) across disease severities; of these patients, 104 had non-severe AA, 43 had severe AA, and 19 had very severe AA. Two hundred and eighty pediatric patients with ITP were enrolled in the study and were an average age of 5 years old (range = 1-14 years) across all disease phases; among them, 155 had newly diagnosed ITP, 55 had persistent ITP, and 70 had chronic ITP.
The investigators found that serum TPO levels were significantly higher in patients with aAA compared with ITP (1,142 vs. 77.99 pg/mL; p<0.001). At a cutoff value of greater than or equal to 302.5 pg/mL, the sensitivity was 99.4% and specificity was 98.21% in distinguishing aAA versus ITP. Among patients with aAA, those with very severe AA had an elevation in TPO levels compared to those with non-severe AA (1,360 vs. 984.4 pg/mL; p<0.05).
Additionally, the study showed that serum TPO levels were significantly lower in patients with chronic ITP compared to newly diagnosed or persistent ITP. In patients with chronic ITP, circulating TPO levels were decreased compared to levels in newly diagnosed ITP and persistent ITP (62.28 vs. 81.56 pg/mL, p<0.01; 62.28 vs. 87.82 pg/mL, p<0.05, respectively).
The authors did not find significant differences in serum TPO levels between male and female patients or between four different age categories.
According to Dr. Wright, the study’s strengths include its large cohort of patients and specifically of pediatric patients with aAA and ITP, which can be a challenge to study. “The study was conducted at a single center over a short period of time, likely improving consistency in subject recruitment and assay results, and the statistic analysis was sound,” Dr. Wright said.
However, Dr. Wright had reservations about the platelet count levels captured in the study. “The median platelet counts seemed high for the disease processes studied. For aAA, median platelet count was 44.46 x 109/L, and 39.53 x 109/L for very severe AA. Most patients with very severe AA have a platelet count of less than 20 x 109/L. Similarly, the median platelet count for ITP was 78.05 x 109/L, while most pediatric patients with ITP present with a platelet count of less than 20 x 109/L.”
The authors found a negative correlation between platelet counts and TPO levels in aAA (rs = -0.3325; p<0.001) as well as ITP (rs = -0.2570; p<0.001). TPO levels were inversely correlated with platelet counts in non-severe AA (rs = -0.3672; p<0.001) and newly diagnosed ITP (rs = -0.3316; p<0.001).
“As a result of the high median platelet counts and platelet counts over 150 x 109/L reported in the study, I question the underlying diagnoses and the cohort of children included in the study,” Dr. Wright said. “It’s possible some of the subjects may have received treatment or were transfused with platelets; however, this was not described in the methods, other than describing that patients with ITP treated with TPO or TPO agonists were excluded. Other treatments, such as corticosteroids, could have impacted serum TPO levels if any of the participants had received treatment.
“Correlation between platelet count and TPO levels may not have been as significant if platelet counts over 100 x 109/L were excluded,” she added.
Another limitation to the study, according to Dr. Wright, is the small number of patients with very severe AA included. According to her, these results “should be confirmed in a more typical cohort of pediatric patients with lower platelet counts and using age- and sex-matched controls, including validation in a prospective cohort.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Chen H, Ma J, Ouyang J, et al. The differences of serum thrombopoietin levels between acquired aplastic anemia and immune thrombocytopenia in pediatric patients. J Pediatr Hematol Oncol. 2024;46(6):281-286.