Jenna presents to the ED with a mild exacerbation of her asthma and a temperature. She seems to have improved and is about to be sent home when the registrar notices her platelet count is 600 x 109.
Will this just resolve, or should we do something about it?
Thrombocytosis is very common and often transient in children when it is secondary. 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. Platelet counts can exceed 900 × 10^9/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, is a myeloproliferative neoplasm. 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 carry a risk 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% with essential thrombocytosis have been found to carry 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 reported a low prevalence of JAK2 mutations in children with ET. Investigations into other genetic mutations associated with ET in children have 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; history of thrombosis; extreme thrombocytosis; cardiovascular risk factors; JAK2 mutation). Clearly, this stratification is not that helpful in children.
As research on children with thrombocytosis is so scant, we base our management on adult guidelines. In adults, those at low risk are treated with low-dose aspirin; other treatments for higher-risk patients include hydroxyurea, interferon alpha, busulfan, anagrelide, and targeted therapy with JAK2 inhibitors (e.g., Ruxolitinib).
In children, there are no consensus guidelines, but some approaches have been published. The general advice is that if the child is asymptomatic, observation and repeat counts should be performed 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.