Soluble thrombomodulin and protein c plasma levels in neonatal sepsis

Sepsis is a systemic response to infection, and it constitutes a major cause of morbidity and mortality in Intensive Care Nursery Unit. Sepsis is associated with endothelial cell activation, a hemostatic profile characterized by activation of the coagulation pathway, and subsequent activation of the fibrinolytic system, which is then followed by the inhibition of the fibrinolytic system. Thrombomodulin [TM] is a membrane glycoprotein in the vascular endothelium and it plays an important physiological role as a cofactor in the thrombin catalyzed activation of protein C [PC]. It is also a specific parameter of endothelial cell injury. The aim of this study was to assess the plasma levels of soluble TM and PC and to clarify their relationships with the severity and outcome of neonatal sepsis. This study was carried out on 40 preterm neonates [20 septic and 20 controls] and 40 fullterm neonates [20 sepstic and 20 controls]. It was done in the Neonatal Intensive Care Unit at El-Minia University Hospital and Biochemistry Department, from December 2001 to May 2002. All neonates were subjected to full history taking stressing upon the risk factors for infection and thorough clinical examination for assessment of gestational age and detection of the clinical signs and severity of sepsis. The laboratory investigations included CBC, CRP, blood cultures and estimation of TM and PC in the plasma by ELISA technique. In this study, plasma levels of TM were significantly higher and plasma levels of PC were significantly lower in neonates with sepsis than those in the controls, in preterm than fullterm both septic and controls, in preterm cases than preterm controls and in fullterm cases than fullterm controls [all p<0.05], but no significant differences of both markers were reported between positive and negative cases of blood cultures [all p >0.5]. There was also a significant increase of TM and decreased PC plasma levels in survivors rather than non survivors both fullterm and preterm cases and in severe, complicated rather than non severe, non complicated septic cases [all p<0.05]. Significant negative correlations were reported between TM and PC in both preterm and full term cases [r=-0.46, p<0.03 and r=-0.51, p <0.02 respectively]; also between TM levels and platelet numbers in both preterm and fullterm cases [r=-0.53, p< 0.01 and r=-0.42, p<0.04 respectively]. The correlations between PC levels and platelet count were significant [r=0.5, p<0.02 for preterm cases and r=0.56, p<0.01 for fullterm cases respectively]; but there were no significant correlations between both TM and PC levels with Hb % and Ieucocytic count [all p>0.05]

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Conclusion: The elevation of plasma TM is frequently seen in neonatal sepsis and circulating TM is a useful marker for evaluating endothelial tissue damage. Protein C serves as an early and highly sensitive marker for hypercoagulable state of sepsis.Both markers are useful indicators for detecting the severity and outcome of neonatal sepsis