Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis

Abstract

JAK2, MPL, and CALR mutations, which underlie essential thrombocythemia (ET) in most adults, are infrequent in children. Consequently, additional tests are needed to confirm pediatric ET diagnoses. We report a child with suspected ET and p JAK2, MPL, and CALR analyses. Serum thrombopoietin was markedly elevated, leading to analysis of the thrombopoietin gene, TPHO, which contains an upstream open reading frame (uORF) known to repress THPO translation. Sequencing revealed a de novo, germline stopgain mutation in the uORF, explaining the elevated thrombopoietin and thrombocytosis. This suggests that screening thrombopoietin levels and, if elevated, THPO 5’ UTR sequencing could be diagnostic.

Extreme thrombocytosis in systemic juvenile idiopathic arthritis. A case report

“…At T3, Tpo level was 46.38 pg/ml. These values were very similar to those reported for healthy children [4] and adults [5], and much lower than values found in adult subjects with thrombocytopenia (476–3,148 pg/ml) (our unpublished data).…”

“…Finally, plasma Tpo levels were also examined at all time-points. Values were consistent with those reported for healthy adults (62.3 to 124 pg/ml [4]) and children (7 to 99 pg/ml [5]), and no significant changes were observed throughout the test period (Table 1). Due to limited availability of blood, it was not possible to measure all cytokines at all time points.…”

Thrombocytosis with acquired von Willebrand disease in an adolescent with sickle cell disease

“…14 Serum TPO level is an important screening test for ET, particularly familial ET if markedly elevated above 1000 pg/mL. 3 TPO in this case was low normal, which suggests that inflammation was an unlikely driver for thrombocytosis. Though the genetic testing performed is not exhaustive and does not exclude other germline or somatic mutations in unidentified genes, our testing did exclude some of the most common reported genetic alterations causing extreme thrombocytosis.…”

“…Thrombocytosis in children is commonly a reactive condition secondary to inflammation, infection, iron deficiency anemia, or asplenia 1,2 and rarely requires intervention. Conversely, primary thrombocytosis is uncommon in pediatrics, but may represent an acquire myeloproliferative disorder or familial thrombocytosis, 3 conditions that may be associated with thrombosis and bleeding. 4 Thrombocytosis is common in children with sickle cell disease (SCD).…”

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics

“…In addition to exonic sequences, mutational analysis might also be extended to include the 5' untranslated regions of genes known to be altered in rare cases of sporadic and hereditary MPN. [16][17] It must be noted that a significant number of MPN patients classified as triple negative have no detectable alternative JAK2 or MPL mutations, nor any evidence of clonal hematopoiesis by X chromosome inactivation patterns. [10][11][12] Whether these cases, analogous to a larger proportion of pediatric patients classified as MPN, truly have a clonal malignancy is questionable.…”