3 Clinical Trials for Various Conditions
Maintenance of adequate anticoagulation or blood thinning is of critical importance when patients are placed on extracorporeal life support, such as extracorporeal membrane oxygenation (ECMO). During ECMO, a patient's entire blood volume is constantly exposed to the artificial surfaces of the ECMO circuit. This exposure activates the clotting cascade, and not only is the circuit at risk for clot formation, but the patient is also at risk for clotting within the body. Hence anticoagulation is vital in allowing the ECMO circuit to support a patient for an extended period of time. Anticoagulation on ECMO is achieved primarily by the use of a blood thinning agent called heparin. Heparin's main mechanism of action is to activate an enzyme called antithrombin III (AT III). AT III deficiency has been shown to be a common finding in pediatric patients requiring ECMO. This deficiency may then result in ineffective blood thinning by heparin. The purpose of this study is to determine how a neonate on ECMO, processes and eliminates a medication called ATryn® from their body. ATryn® is a form ATIII that is made from goat's milk. This will ultimately aid in establishing standardized dosing for the use of ATryn® in this patient population.
Infants are placed on ECMO for correction of reversible respiratory failure. Often, because a few of the reasons for respiratory failure show us similar things in the baby, it is difficult to determine exactly which is causing the biggest problem. We are now capable of measuring certain cells and proteins in these infants that may help us more accurately diagnose the exact problem. We hypothesize that infants placed on ECMO will show unique antibody-secreting cells responses and patterns of cytokine and chemokine (protein) response to illness and to the ECMO circuit. If we find unique patterns to these cells or proteins, they may be able to predict outcomes or guide treatment of these infants.
The potential role of ATIII in achieving and maintaining adequate anticoagulation in pediatric patients on the heart-lung machine has recently taken on increased importance as caregivers strive to mitigate the risk for clinically significant clotting problems. It is known that ATIII levels are decreased in normal neonates and infants less than 6 months of age relative to older children and adults and become even further decreased in critically ill neonates and infants, including those with congenital heart disease. The current utilization of ATIII in the context of support on a heart-lung machine is based on pharmacokinetic data derived from adult subjects with congenital ATIII deficiency. There is a gap in knowledge as to the appropriate frequency of ATIII repletion, best method of monitoring, and mode of administration in critically ill neonates and infants receiving support on a heart-lung machine.Our long-term goal is to determine if antithrombin (ATIII) can effectively change the coagulation system in patients undergoing heart-lung machine support. The objective of this proposal, which is our first step in pursuit of that goal, is to determine the pharmacokinetics of ATIII in neonates and infants. Our central hypothesis is that ATIII will have different pharmacokinetic properties in neonates and infants than adults and these properties will be affected by the use of heart-lung machine. This research will result in critical data on the pharmacokinetics of ATIII in neonates and infants receiving heart-lung machine support. This contribution is significant because it is the first step in a continuum of research that is expected to lead to the development of a therapeutic strategy employing ATIII that will facilitate improved modulation of the coagulation cascade to prevent significant clotting and bleeding complications in pediatric patients requiring heart-lung machine support.