Study of protein C, protein S, and antithrombin III in newborns with sepsis

Pediatr Crit Care Med. 2010 Jan;11(1):52-9. doi: 10.1097/PCC.0b013e3181c59032.


Objective: The aim of this study is to clarify the effect of sepsis on the physiologic inhibition system of coagulation including protein S, protein C, and antithrombin III, and to study their further effect on thromboembolic accidents of septic newborns.

Design: Clinical study including 30 septic neonates and 30 normal neonates served as control group.

Data sources: MEDLINE, pediatric textbooks, Neonatal Intensive Care Unit, Department of Pediatrics, Faculty of Medicine, Cairo University.

Results: The results of this study showed marked decrease in the level of the physiologic inhibition system of coagulation including antithrombin III, protein C, and protein S in 100% of cases, compared to the control group (p < .001). Disseminated intravascular coagulation developed and death occurred in 33.3% of cases, necrotizing enterocolitis developed in 40% of cases, rectal bleeding developed in 33.3%, hematuria developed in 20% of cases, hematemesis developed in 26.7% of cases, intracranial hemorrhage developed in 23.3% of cases, and convulsions developed in 23.3% of cases.

Conclusions: In this study we have tried to evaluate the effect of sepsis on the physiologic inhibition system of coagulation in neonates. We should expect the effect of sepsis and its severity and perform the necessary laboratory investigations for coagulation including antithrombin III, protein C and protein S levels to help prevent thromboembolic accidents in neonates with sepsis, including disseminated intravascular coagulation, necrotizing enterocolitis and intracranial hemorrhage. Based on the findings of our study and the results of the other studies, we are in agreement that protein C is a very useful biomarker in severe sepsis, and it is a possible tool for monitoring treatment with activated protein C. We also encourage further placebo-controlled clinical trials to investigate the role of activated protein C and antithrombin III in severe neonatal sepsis and especially in the states before disseminated intravascular coagulation and the disseminated intravascular coagulation states, on the condition that they are guided by the experience and recommendations gained from the PROWESS, ENHANCE, and RESOLVE clinical trials. Protein C might be more effective if dosed according to protein C levels rather according to weight. Furthermore, we encourage future research on activated protein C mutants, which are anticipated to appear very soon because they can reduce some side effects associated with the use of recombinant human activated protein C, such as intracranial hemorrhage and bleeding tendencies, because they have reduced anticoagulant activity while retaining the cytoprotective effects.

MeSH terms

  • Antithrombin III / analysis
  • Antithrombin III / metabolism*
  • Blood Coagulation / physiology
  • Enterocolitis, Necrotizing / epidemiology
  • Enterocolitis, Necrotizing / etiology
  • Enterocolitis, Necrotizing / prevention & control
  • Humans
  • Infant, Newborn
  • Intracranial Hemorrhages / epidemiology
  • Intracranial Hemorrhages / etiology
  • Intracranial Hemorrhages / prevention & control
  • Protein C / analysis
  • Protein C / metabolism*
  • Protein S / analysis
  • Protein S / metabolism*
  • Sepsis / complications
  • Sepsis / physiopathology*
  • Severity of Illness Index
  • Thromboembolism / prevention & control


  • Protein C
  • Protein S
  • Antithrombin III