Primary thrombocytosis in children

Abstract

Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outcomes in adults have been well delineated with defined recommendations for risk stratification and treatment. This is not the case for pediatric patients, for whom there is neither a standard approach to workup nor any consensus regarding management. This review will discuss thrombocytosis in children, including causes of thrombocytosis in children, the limited knowledge we have regarding pediatric primary thrombocytosis, and our thoughts on potential risk stratification and management, and future questions to be answered by laboratory research and collaborative clinical study. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o ngenerally on control at the transcriptional level. 13 This rate depends upon TPO binding to its receptor, which in turn depends upon how many TPO-R bearing cells are accessible, as well as how many receptors they express.14 Low platelet counts will lead to decreased TPO clearance (less receptors in the circulation) and therefore increased levels of TPO; the reverse occurs with higher platelet counts, i.e. thrombocytosis. There are variations to this basic principal, for example in the setting of idiopathic thrombocytopenia (thrombocytopenia due to destruction). In these cases, the number of megakaryocytes and megakaryocyte mass may also influence TPO regulation and circulating levels. 15,16 Causes of reactive thrombocytosis in childrenSecondary, or reactive, thrombocytosis is a common occurrence in children. It has been reported to occur in 6-15% of hospitalized children, with variations based on age. Most of these children had thrombocytosis that could be characterized as mild, but others transiently reached levels over 900,000. [17][18][19][20] Causes of secondary thrombocytosis are many and varied (Table 1). Infection is the most common, including viral and bacterial pathogens, and both acute and chronic infections. Especially in children under one year of age, any infection seems capable of triggering a high platelet count. Inflammatory diseases, e.g. Kawasaki disease, rheumatoid arthritis, and inflammatory bowel disease, are commonly associated with reactive thrombocytosis, as are hypoxia, trauma, blood loss, and malignancy. 19,21,22 Iron deficiency also seems to be a frequent cause of secondary thrombocytosis. 20 It is believed that underlying mechanisms of secondary thrombocytosis can be explained by upregulation of TPO expression and resultant increased TPO levels. Hepatic TPO mRNA expression is increased with inflammation. Figure 1 shows our groups' proposed diagnostic algorithm for approaching patients with elevated platelets. Evaluation for secondary causes, such as iron deficiency or inflammatory or infectious disorders is conducted. Iron deficiency and othe...

Bone marrow histology for the diagnosis of essential thrombocythemia in children: a multicenter Italian study

“…finding in children. 8 Most cases are secondary/reactive forms, which spontaneously normalize over time. Rare hereditary thrombocytosis has also been documented.…”

Altered Hematological and Biochemical Parameters in Schoolchildren Living in an Agricultural Community of Merida State, Venezuela

“…A high percentage (46%) of the children living in the studied agricultural community of Merida had thrombocytosis, generally considered a platelet count of more than 450 × 10 3 /µL. According to Kucine et al [51], thrombocytosis is now a common finding in the complete blood count of children. It is often transient and occurs secondary to various underlying medical disorders, usually inflammatory, because an increase in the platelet count is one aspect of the acute phase reaction.…”

“…It is often transient and occurs secondary to various underlying medical disorders, usually inflammatory, because an increase in the platelet count is one aspect of the acute phase reaction. This occurs more frequently in younger children, either because of the immaturity of their innate and/or adaptive immunity, or because they have more frequent infections [51]. According to its origin, thrombocytosis is classified into primary and secondary forms.…”

“…Primary thrombocytosis is an extremely rare clonal disease in childhood with an incidence of one per million children; the platelet count is generally above 1000 × 10 3 /µL and may be associated with hemorrhagic events. Secondary or reactive thrombocytosis is very common in pediatric age and is due to a variety of conditions, such as bacterial and viral infections, inflammatory diseases, recent surgery, malignancy, iron, vitamin E and B12 deficiency, hemolytic anemia, allergic reactions, nephritis, pancreatitis, and side effects of some medications [51]. From the interviews conducted with the parents of farm children, all of them were either occupationally or environmentally exposed to pesticides; hence, there was concern of the increased risk of these children to develop inflammatory or malignant diseases in childhood or later in life.…”

Genetic analysis of five children with essential thrombocytosis identified mutations in cancer-associated genes with roles in transcriptional regulation

“…It occurs less frequently and with more favorable outcomes in children than in adults. The proportions of pediatric patients with mutations in JAK2, MPL, and CALR (the genes most commonly mutated in adult patients) seem lower than in adults, [1][2][3][4] raising the question of what alternative mutations may be contributing to disease in this population. Overall, the genetic landscape of pediatric ET has not been thoroughly evaluated.…”