Antithrombin and Activated Protein C in Pediatric Sepsis: Prospective Observational Study of Outcome

Objectives: To assess antithrombin and activated protein C (aPC) levels in relation to disseminated intravascular coagulation (DIC) and severe outcomes in pediatric sepsis.

Design: Prospective, observational study conducted between April 2023 and October 2024. Coagulation profiles including conventional coagulation, antithrombin activity, and aPC were obtained at PICU admission.

Setting: PICU in the Vietnam National Children's Hospital, Hanoi, Vietnam.

Subjects: PICU admissions, 1 month to 18 years old, with sepsis.

Interventions: None.

Measurements and main results: One hundred thirty children (78 males; median age 7.5 mo) with mortality 23/130 (17.7%). The prevalence of overt DIC was 37 of 130 (28.5%). Nonsurvival at 28 days, compared with survival, was associated with hemorrhage and/or thrombosis at presentation, and higher number of dysfunctional organs, and overt DIC. Those with overt DIC, compared with not, had longer activated partial thromboplastin time, higher international normalized ratio and d-dimer, and lower antithrombin, and aPC. Activity of antithrombin and aPC correlated inversely with the Vasoactive-Inotropic Score in survivors (p = 0.002 and 0.009, respectively). Patients with a cutoff value for antithrombin less than 63.5% had a mortality risk with area under the receiver operating characteristic (AUROC) curve 0.64, with sensitivity 0.51 and specificity 0.74, and positive predictive value 0.30. Regarding overt DIC, a cutoff value for antithrombin less than 55.5% had an AUROC 0.78, sensitivity 0.72 and specificity of 0.73, and positive predictive value 0.52.

Conclusions: In this observational study of pediatric sepsis patients, first 24-hour coagulation data in those who did not-survive to 28 days, vs. survivors showed an associated prior lower level of antithrombin in nonsurvivors. Furthermore, using the outcome of overt DIC and nonovert DIC in the first 72 hours, we found that lower levels of antithrombin or aPC are each associated with overt DIC and nonovert DIC in pediatric sepsis. Further validation work is needed in larger case series of pediatric sepsis.