Jenna presents to ED with a mild exacerbation of her asthma and a temp. She seems to have improved and is about to be sent home when the registrar notices that her platelet count is 600 x 109.
Will this just resolve or should we do something about it?
Thrombocytosis is very common and is often transient in children when it is a secondary thrombocytosis. Primary (or essential thrombocytosis) is less common in children. It is better understood in adults where it is part of the family of myeloproliferative neoplasms and can cause complications.
What’s the definition of thrombocytosis?
Thrombocytosis is usually categorised into mild, moderate, severe or extreme.
Mild thrombocytosis: 450-600 x 109/L
Moderate thrombocytosis: 600-900 x 109/L
Severe thrombocytosis: 900-1000 x 109/L
Extreme thrombocytosis: over 1000 x 109/L
What causes secondary thrombocytosis?
In children, we frequently see secondary thrombocytosis. In fact, 6-15% of hospitalised children have high platelets. The platelet levels can reach over 900x 109/L even in secondary thrombocytosis.
This can occur most frequently with infection; but also with inflammatory conditions (e.g. Kawasaki disease, rheumatoid arthritis, inflammatory bowel disease); in acute care (e.g. hypoxia, trauma, blood loss) and in haematology/oncology (e.g.malignancy, iron deficiency).
What’s the significance of essential thrombocytosis in adults?
In adults, essential thrombocytosis, along with polycythaemia vera and primary myelofibrosis, are part of the family of myeloproliferative neoplasms. Patients can be at risk of thrombosis or bleeding, and also splenomegaly, bone marrow fibrosis, and the potential to transform into acute myeloid leukaemia. Even the hereditary forms have risks of complications.
What’s the relevance of the JAK2 gene in adults?
Since the JAK2 V617F mutation was discovered in 2005, our understanding of essential thrombocytosis in adults has improved. 95% of adults with polycythaemia vera and 50% of adults with essential thrombocytosis have been found to have the JAK2 mutation.
Associated mutations have also been found in cMPL and there is an overexpression of the PRV-1 gene.
Does the JAK2 mutation help children?
JAK2 mutations are far less common in children, and many studies have found a low prevalence of the JAK2 mutation in children with ET. Investigation for other genetic mutations connected with ET in children has also proved fruitless.
While the JAK2 mutation can be diagnostically useful in adults, this isn’t really the case in children.
How should we manage thrombocytosis in children?
In adults, management of thrombocytosis is based on risk stratification (age over 60; thrombosis history; extreme thrombocytosis; cardiovascular risk factors; JAK2 mutation). Clearly, this stratification is not that helpful in children.
As the research on children with thrombocytosis is so scant, we derive our management from adult guidelines. In adults, those who are low-risk are treated with low-dose aspirin; other treatments for higher-risk patients include hydroxyurea, interferon alpha, busulfan, anagrelide, and targeted therapy for JAK2 inhibitors (Ruxolitinib).
In children, there are no consensus guidelines, but some approaches have been published. The general advice is that if the child is asymptomatic, there should be observation and repeat of counts every 3-6 months. If there is an additional thrombophilia risk then we should consider low-dose aspirin. If the child fails on low-risk therapy, then these other medications can be considered.
Jenna’s platelet count was repeated three months later when she was well, and had returned to a normal 310 x 109/L. This was a simple case of secondary thrombocytosis due to intercurrent illness.
Fu R, Zhang L, Yang R. Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment. Br J Haematol. 2013;163(3):295-302.
Kucine N, Chastain KM, Mahler MB, Bussel JB. Primary thrombocytosis in children. Haematologica. 2014;99(4):620-8.
Nakatani T, Imamura T, Ishida H, et al. Frequency and clinical features of the JAK2 V617F mutation in pediatric patients with sporadic essential thrombocythemia. Pediatr Blood Cancer. 2008;51(6):802-5.