Abstract
BACKGROUND: Platelets release different substances when activated, such as during critical illness when children are inflamed. We explored the associations of catheter-associated deep venous thrombosis (CADVT), clinically relevant bleeding (CRB) and prophylactic enoxaparin with biomarkers of platelet activation and inflammation in critically ill children. METHODS: We analyzed platelet-poor plasma collected from critically ill children <18 years old with central venous catheter (CVC) enrolled in 2 multicenter studies conducted between 2017 and 2024. Blood was obtained on the day of, day after and 4 days after insertion of the CVC. Children were monitored daily for CRB and systematically surveilled for CADVT using ultrasonography. P-selectin, CD40L, platelet factor 4, RANTES, human thrombospondin 1, IL-1β, IL-2, IL-6, IL-8 and TNF-α were measured using immunosorbent assays. RESULTS: We studied plasma from 126 children (median: 9.6 years; interquartile range: 1.2, 15.3 years), of whom 24 received prophylactic enoxaparin. CADVT developed in 37.6 % and CRB in 31.0 % of children. Among children without prophylactic enoxaparin, CADVT was associated with high P-selectin and IL-6. A biomarker-augmented model with P-selectin and IL-6 seemed to perform better than a clinical model with age group, severity of illness and platelet count in identifying critically ill children with CADVT. CRB was associated with high platelet factor 4, while prophylactic enoxaparin was associated with high TNF-α. CONCLUSIONS: Our findings suggest the role of platelet activation in CADVT in critically ill children. Once confirmed, these biomarkers may be used to identify critically ill children who would benefit from pharmacologic prophylaxis.