Neonatal Sepsis: A Challenge in Hemostaseology

Abstract

Several therapeutic approaches to sepsis and disseminated intravascular coagulation (DIC) have shown promising results in animal models. Large controlled trials in humans, however, have failed to show a clearly beneficial effect of a single drug or substance on outcome and survival so that treatment remains uncertain. As one researcher stated: ". . . sepsis is a classical example of a disease greater than the sum of its parts; it is a complex process in which intervention in one area might have only a modest effect on the final outcome." We believe that the complex pathophysiological setting of septic shock will undoubtedly require a multifaceted approach. Consequently, we attempt to arrest DIC and restore adequate tissue perfusion by intervention with heparin, AT and if possible protein C (PC) in the earliest stage of the disease, with the aim of blocking ongoing microthrombus formation and to support fibrinolysis. Growing understanding of the basic underlying mechanisms teaches us how to successfully stabilise the individual decompensated sub-systems like coagulation in septic patients. We should learn to accept these steps to reach the goal of a better outcome in terms of survival in this devastating illness.

Protein C preserves microcirculation in a model of neonatal septic shock

“…21 Our study provides new affirmative data for the clinical observation that the use of protein C results in an improvement of sepsis-induced microcirculatory dysfunction. 14,22 In accord with the findings of De Backer and colleagues, sepsis-induced alteration of the MAP was positively influenced by rhAPC. 22 The De Backer study demonstrated a rapid increase in MAP shortly after infusion of rhAPC in patients with septic shock.…”

“…26 We and others have shown that hPC is effective in the treatment of neonates and children with sepsis-induced purpura fulminans without increasing the risk of hemorrhage. 14,[26][27][28] In porcine animal models, however, activation of hPC is known to be less effective. Thus, a benefit was doubtful and we decided not to use it in this study.…”

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

“…43 As the adult literature supports efficacy of antithrombotic agents, some centers also report routine utilization of heparin, ATIII, and/or PC in neonatal sepsis. 44 Studies of these antithrombotic agents in neonates are generally small and uncontrolled, but support that antithrombotic agents may have clinical effects in early postnatal life. Kreuz et al 44 reports the administration of 100 IU heparin per kg each day for neonatal sepsis.…”

“…44 Studies of these antithrombotic agents in neonates are generally small and uncontrolled, but support that antithrombotic agents may have clinical effects in early postnatal life. Kreuz et al 44 reports the administration of 100 IU heparin per kg each day for neonatal sepsis. Activated PC concentrates are being administered to older patients with septic shock, showing promising results.…”

“…47,48 PC administered to seven neonates with septic shock and purpura fulminans in an uncontrolled fashion resulted in improved circulating PC levels, with 100% survival. 44 In addition to inhibition of thrombin formation and reduction in levels of plasminogen activator inhibitor type 1, activated PC has anti-inflammatory properties to reduce activation/adhesion of neutrophils through decreased production of tumor necrosis factor a and decreased expression of endothelial E selectin. 49 ATIII is another therapeutic option that attenuates organ damage by decreasing microthrombus formation and endothelial injury.…”