Coagulation, Inflammation, and the Risk of Neonatal White Matter Damage

Abstract

Indicators of coagulation activation are sometimes increased in the blood of newborns and adults who have a systemic inflammatory response. These coagulation factors have the ability to exacerbate inflammation, which in turn can promote coagulation. Therapies directed solely at coagulation factors and therapies directed solely at inflammation factors have not proved effective in reducing mortality in adults with a systemic inflammatory response syndrome and multiorgan dysfunction (SIRS/MOD). On the other hand, the only therapy that has reduced mortality in SIRS/MOD is activated protein C, which has both anti-coagulation and anti-inflammatory effects. This and other observations support the view that activated coagulation factors enhance inflammation. Since newborns at risk of cerebral white matter damage and cerebral palsy are more likely than their peers to have a systemic inflammatory response, which is sometimes accompanied by elevated blood levels of coagulation factors, we suggest that activated coagulation factors contribute to the occurrence of cerebral white matter damage by exacerbating inflammatory phenomena, rather than by occluding cerebral blood vessels. Preterm newborns with respiratory distress syndrome and term newborns who develop cerebral palsy tend to have elevated blood levels of coagulation factors. In this essay, we suggest that these coagulation factors, when activated, produce their effects not so much by promoting coagulation as by promoting inflammation, a view supported by studies of adults with a systemic inflammatory response syndrome with multiorgan dysfunction (SIRS/MOD). We also suggest that activated systemic coagulation factors in the preterm newborn contribute to cerebral white matter damage (WMD) and to its clinical sequelae, including cerebral palsy (CP). NEWBORNS Respiratory distress syndrome (RDS) in preterm newborns.Fibrin is a major part of hyaline membranes, which are viewed as locally produced clots in neonatal RDS (1, 2). Indeed, the severity of RDS has been linked to the systemic concentration of thrombin-antithrombin III complex (3). In addition, preterm babies with RDS are more likely than their peers to have systemic activation of inflammation (4, 5). We do not yet know if products of coagulation and inflammation co-occur in the blood of infants destined to develop bronchopulmonary dysplasia.In newborn immature sheep with RDS, inflammation and clotting are activated shortly after birth (6). "Because activation of clotting and platelet activation are found later than activation of inflammation," Jaarsma and colleagues recently wrote, "we consider activation of clotting is not causative in RDS, but is activated secondary to activation of inflammation" (6).We postulate that this scenario of inflammation promoting coagulation also applies to neonatal WMD. Moreover, we postulate that inflammation promotes coagulation, which in turn further promotes inflammation (Fig. 1).CP in term newborns. Support for the systemic activation of both inflammation and coagulation in newb...

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Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

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