Platelet reactivity in young children undergoing congenital heart disease surgery: a NITRIC randomized clinical trial substudy

The international NITRIC trial studied the hypothesis that nitric oxide (NO) applied into the cardiopulmonary bypass (CPB) oxygenator in infants would improve recovery after heart surgery. In a substudy, we evaluated the effect of NO applied into the CPB oxygenator on the (re)activity of platelets measured as fibrinogen binding (platelet aggregation) and P-selectin expression (platelet degranulation) in young children. Platelet activity (without agonist exposure) and reactivity (after stimulation by an agonist) was studied in a single center substudy of the NITRIC trial, a multicenter, randomized trial that studied administration of 20 parts per million (ppm) NO during CPB in children younger than 2 years. Blood was collected at 4 time points (T1- T4); before CPB, after CPB start, before and after weaning. Flow cytometry-based platelet activity and reactivity in the presence of 5 agonists was tested. Differences on P-selectin expression and fibrinogen binding (median fluorescence intensity (MFI)) were analyzed with mixed effect modelling (MEM). Blood samples were obtained in 22 patients allocated to NO and 20 controls. Platelet counts dropped after T1 due to the hemodilution of blood in all patients (p < 0.001). Beta coefficients for NO allocation derived from the MEM models on fibrinogen binding and P-selectin expression were small (standardized beta coefficients on fibrinogen binding were 0.07[0.03, 0.11] and on P-selectin expression 0.05[0.03, 0.08]) and non-significant. CPB duration did not affect platelet reactivity (standardized beta coefficients 0.09[0.02, 0.12] with p > 0.27) in any of the MEMs. 20 ppm NO administration in the sweep gas of the CPB oxygenator did not affect platelet reactivity in young children undergoing heart surgery. Interestingly, duration of CPB exposure also did not have an effect on platelet (re)activity. ANZCTR, ACTRN12617000821392. Registered 5 June 2017, https://anzctr.org.au/