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Low Plasma Protein C Values Predict Mortality in Low Birth Weight Neonates With Septicemia

Background: Septicemia activates coagulation and decreases activated protein C (APC). Low APC in adults is associated with multiorgan dysfunction and mortality, but such data in neonates are lacking. Being deficient in APC, neonates may be especially vulnerable to the effects of low APC. Methods: This cohort study was conducted on 40 neonates with severe bacterial septicemia to determine the relationship between plasma APC values and mortality, time to mortality, and hazard of dying. Low birth weight neonates with sepsis, organ dysfunction, and systemic inflammatory response syndrome were enrolled after parental consent. Plasma APC was assayed at enrollment and subjects were followed for 14 days from enrollment. Low birth weight neonates, who had major malformations, severe birth asphyxia, or received blood products before APC assay, were excluded. Primary outcome: comparison of APC level between survivors and nonsurvivors. Secondary outcomes: survival with low versus normal APC; and hazard ratio of APC, adjusted for birth weight, Score for Neonatal Acute Physiology and number of affected organs. Results: Forty of 74 eligible neonates were included. Twenty-five of the enrolled neonates died within 14 days. APC levels in nonsurvivors were lower than in survivors [median (interquartile range) %, 15 (4.5–21) versus 33 (18–55); P < 0.001]. Ten nonsurvivors versus 1 survivor had low APC (P = 0.03). Positive predictive value (PPV) of low APC values for mortality was 90.9%. Survival in the low APC group (n = 11) was shorter than in normal APC group [median (95% confidence interval) days, 3 (2.3–3.7) versus 10, P value <0.001]. APC value was independently associated with hazard of dying [adjusted risk 0.95 (95% confidence interval 0.92–0.99), P = 0.02]. Each 1% rise in APC decreased the hazard of dying by 5%. Conclusions: Mortality was higher and duration of survival shorter in septic neonates with lower plasma ACP. The latter was an independent predictor of the hazard of dying.