175 - Inflammation, Anemia and Vitamin D Status Determine Infant Thrombocytosis Risk

Publication Number: 2169.175

Sahaana S. Rajagopalan, Davidson College, Newark, DE, United States; Brian M. Dulmovits, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Matthew Devine, Childrens Hospital of Philadelphia, Collingswood, NJ, United States; Christopher Thom, CHOP/UPenn, Philadelphia, PA, United States

Background: Extreme thrombocytosis (EXT, >1000x10^3 platelets/ml blood) occurs in infants due to infection, inflammation, and/or anemia. EXT can present diagnostic dilemmas, sometimes prompting invasive testing and anticoagulation therapy. We previously identified heightened EXT rates in hospitalized infants compared with older children, but this analysis largely excluded ex-preterm infants at increased risk for infections and anemia - factors that promote thrombocytosis and EXT.

Objective: Our objectives were to 1) define EXT rates, etiologies, and sequelae among infants hospitalized in tertiary neonatal intensive care units (NICUs) to assist clinical decision-making and 2) determine factors that drive thrombocytosis and EXT in preterm and full-term patients.

Design/Methods: Retrospective analysis of thrombocytosis (>500x10 3 platelets/ml) and EXT cases among 20,818 infants hospitalized in tertiary NICUs from 2011-2023.

Results: Our results revealed thrombocytosis in 3% of all patients (8% of preterm infants). Both estimates were significantly lower than the incidence of thrombocytosis in pediatric patients in a quaternary NICU (15%). EXT was also reduced in our tertiary unit (0.08% vs 0.5% in quaternary NICU). Thrombocytosis was associated with leukocytosis and relative anemia, but not with thrombotic or bleeding complications. Vitamin D deficiency can drive thrombocytosis in adults and Vitamin D level was inversely corelated with platelet count among infants with thrombocytosis.

Conclusion(s): Our findings suggest that Vitamin D supplementation among ex-preterm infants reduces thrombocytosis and EXT incidence, as opposed to developmental differences and/or organ immaturity in these patients. These results provide important context for clinical interpretations and responses to thrombocytosis in the preterm infant population.

Figure 1. Thrombocytosis and extreme thrombocytosis (EXT) rates among infants hospitalized at a tertiary vs quaternary care units, including breakdown by gestational age for preterm infants.
A) Blood counts and demographics for infants with thrombocytosis or EXT in our cohort of
20,818 total infants. Blood counts represent values at the time of thrombocytosis or EXT. PLT,
platelet count. HGB, hemoglobin. RBC, red blood cell count. WBC, white blood cell count.
B) Thrombocytosis rates among infants hospitalized at our tertiary care unit, including a
breakdown of those both preterm ( <37 weeks gestation at birth). Reference comparison to
historical data from a quaternary referral NICU [1].
C) EXT rates among infants hospitalized at our tertiary care unit, including a breakdown of those
both preterm ( <37 wks gestation at birth). Reference comparison to historical data from a
quaternary referral NICU [1].
D) Breakdown of thrombocytosis rates based on degree of prematurity.
E) Breakdown of EXT rates based on degree of prematurity.

Figure 2. Platelet count is associated with altered white blood cell count and Vitamin D level, with thrombocytosis occurring most frequently around 3-4 weeks of life in temporal relation with hemoglobin nadir.
A) Heat map depicting r2 values with platelet count (PLT) associations for the indicated traits.
Traits with significant correlation, as defined by a line of best fit slope that deviates significantly
from 0 are indicated with an asterisk [Pr(>|t|) <0.05]. Red dots indicate positive correlation and
blue dots indicate negative (inverse) correlation. A breakdown of quantitative leukocyte
parameters is shown below the dashed line, with Monocyte (Mono) and Lymphocyte (Lym)
counts showing significant direct association with PLT count.
B) Scatterplot comparing platelet count vs white blood cell count in unique infants with
thrombocytosis (maximum 1 dot per infant). Line of best fit is shown in red with standard
deviation in gray. Pr(>|t|)=1.8x10-2

, meaning the slope of this line significantly differs from 0.
C) The incidence of thrombocytosis peaks in the 3rd week of life in this patient cohort. This
histogram includes episodes of recurrent thrombocytosis that occurred in some patients.
D) Heat map depicting r2 values with platelet count (PLT) associations for the indicated traits.
Blue dots indicate negative (inverse) correlation.
E) Scatterplot comparing platelet count vs Vitamin D level in infants with thrombocytosis,
including patients in tertiary and quaternary NICUs. Line of best fit is shown in red with standard
deviation in gray. Pr(>|t|)=2.9x10-11, meaning the slope of this line significantly differs from 0.