Extreme thrombocytosis is associated with critical illness and young age, but not increased thrombotic risk, in hospitalized pediatric patients

Abstract

Background: Extreme thrombocytosis (EXT, platelet count > 1000 × 10 3 /μL) is an uncommon but potentially clinically significant finding. Primary EXT in the setting of myeloproliferative disorders is linked to thrombotic and/or bleeding complications more frequently than secondary EXT, which typically occurs in reaction to infection, inflammation, or iron deficiency. However, comorbidities have been reported in adults with secondary EXT. Clinical implications of EXT in children are not well defined, as prior studies targeted small and/or specialized pediatric populations. Objectives: Our objectives were to determine etiologies and sequelae of EXT in a hospitalized general pediatric patient population. Patients and Methods: We retrospectively analyzed EXT cases from a single-center pediatric cohort of ~80 000 patients over 8 years. Results: Virtually all cases (99.8%) were secondary in nature, and most were multifactorial. Many cases of EXT occurred in children under 2 years old (47%) and/or during critical illness (55%). No thrombotic or bleeding events directly resulted from EXT, confirming a paucity of clinical complications associated with EXT in pediatric patients. There were indications that neonatal hematopoiesis and individual genetic variation influenced some cases, in addition to certain diagnoses (eg, sickle cell anemia) and clinical contexts (eg, asplenia). Conclusion: Our findings confirm that thrombotic events related to EXT are rare in pediatric patients, which can inform the use of empiric anti-platelet therapy.

Pathophysiology, classification, and complications of common asymptomatic thrombocytosis in newborn infants

“…33) However, reactive thrombocytosis, notably extreme thrombocytosis, in A c c e p t e d A r t i c l e newborn infants does not seem to be associated with an increased risk of hemorrhagic or thromboembolic complications. 24,26,28,29) Preterm infants with a gestational age < 32 weeks and thrombocytosis had a higher incidence of retinopathy of prematurity according to Del Rey Hurtado de Mendoza et al 4) Conversely, other studies reported that thrombocytopenia, not thrombocytosis, is a risk factor for retinopathy of prematurity. 34) Thus, the association between thrombocytosis and retinopathy of prematurity remains controversial.…”

“…Infectious pathogens and immune complexes formed by them can activate platelets, which then secrete molecules to activate immune reactions [ 23 ]. Thom et al [ 24 ] suggested that rebound vigorous multilineage hematopoiesis following myelosuppression due to critical illnesses such as infection, inflammation, or iron deficiency can lead to hyperactive bone marrow and result in thrombocytosis.…”

Essential Thrombocythemia in Children and Adolescents

“…Moreover, many interleukins (IL) involved in the inflammation processes, mostly IL-6 and IL-11, can stimulate the platelet production in the liver [ 27 , 28 ]. These processes are highly active during childhood: ST is reported in 6–15% of hospitalized children, and up to 1% of children in intensive care units show platelet counts exceeding 1000 × 10 9 /L [ 5 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

“…Infections, both bacterial and viral, are common causes of thrombocytosis in infants (75% of cases [ 31 ]), and children (47% [ 33 ]), mostly of the respiratory and urinary tracts. All other pediatric inflammatory conditions are associated with ST [ 34 ], in particular those seen in young children, such as Kawasaki disease [ 36 ], Schoenlein–Henoch syndrome, coeliac disease as well as rheumatic diseases and damages to tissues due to trauma, surgery or burns [ 8 ].…”

“…In fact, neither thrombotic nor hemorrhagic complications were seen in more than 4000 reported children with ST [ 32 ]. In 855 children affected by extreme thrombocytosis, Thom et al reported 22 thromboses, all related to underlying conditions, and no hemorrhages [ 33 ].…”