Critical Illness in Children Induces a Platelet Biochemical Fatty Acid Deficiency

Introduction: Bleeding risk in critically ill children does not directly correlate with the degree of thrombocytopenia suggesting platelet function as a key driver of hemostasis. Platelets use specialized lipid metabolism to activate and aggregate; yet, the lipidomic biology of platelet dysfunction in pediatric critical illness is poorly understood. We hypothesized that platelets of children with critical illness display impaired lipid metabolism when compared to healthy controls.


Methods: We conducted a pilot prospective cohort study of non-obese children less than 18 years of age admitted to the PICU with organ dysfunction (defined by p-SOFA scoring). We excluded septic children, those on extracorporeal therapies or admitted following cardiopulmonary bypass. We analyzed the fatty acid profile within isolated platelets using GC mass spectrometry and compared the results to a cohort of healthy children.


Results: Nine children were enrolled. Median (IQR) age was 7.8 (5.1-11.3) years and 5/9 were male sex. Two children were critically ill (with pulmonary, cardiac and hepatic dysfunction). The median mole percentage of arachidonic acid (AA) in the platelets of the critically ill was nearly two-fold lower than that of healthy children (4.7% vs 7.8%). Similarly, the % of precursors of AA were two-fold lower in the critically ill as compared to healthy controls (Dihomo-γ-linolenic acid 0.8% vs 1.9% and γ-linolenic acid 0.2% vs 0.5%). Additionally, mole percent of mead (0.09% vs 0.05%), stearic (18.5% vs 10.1%), oleic (23.4% vs 20.3%) and behemic acid (0.13% vs. 0.09%) were all higher in the platelets of the critically ill as compared to healthy children. Major fatty acids on the n3 pathway (ALA, EPA, DHA), showed no significant differences between the two cohorts.


Conclusions: Decreases in omega-6 fatty acids were observed in the platelets of critically ill children with organ dysfunction with compensatory increases in the n9 fatty acids saturated fatty acids compared to healthy controls. Since AA and its metabolites are required for platelet aggregation, these results suggest that platelet dysfunction in pediatric critical illness may be related to altered platelet lipid metabolism that mimics essential fatty acid deficiency. We speculate altered platelet lipid profiles drive hemostatic dysfunction.