Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00165906
Status:
COMPLETED
Last Update Posted:
2013-11-21
First Post:
2005-09-09
Brief Title:
Thrombin Generation in Neonates
Sponsor:
Emory University
Organization:
Emory University
Study Overview
Official Title:
A Pilot Study Examining Thrombin Generation in the Neonatal Population
Status:
COMPLETED
Status Verified Date:
2013-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Children having open heart surgery must be on a heart-lung bypass machine It is essential that the blood in the heart-lung machine does not clot This is accomplished by giving a drug called heparin a blood thinner
The process of making a clot involves a lot of steps One of the steps involves a protein called thrombin Heparin acts on thrombin to keep blood from clotting A technique has been developed to measure the bloods ability to generate thrombin The bloodss ability to generate thrombin is measured by a thrombin generation curve TGC This curve would be very helpful to know when choosing the dose of heparin We havent found any studies using TGC in babies less than a month old
We want to do a study comparing the TGC in 10 newborns without a heart defect to the TGC in 10 newborns with a congenital heart defect To do this we will need one sample of blood the sample we need is 3 cc which is a little more than 12 teaspoon The blood sample for both groups is to be taken from the intravenous catheter IV the child will have placed for surgery The newborns without a heart defect will be children having surgery for a non-cardiac problem
The process of making a clot involves a lot of steps One of the steps involves a protein called thrombin Heparin acts on thrombin to keep blood from clotting A technique has been developed to measure the bloods ability to generate thrombin The bloodss ability to generate thrombin is measured by a thrombin generation curve TGC This curve would be very helpful to know when choosing the dose of heparin We havent found any studies using TGC in babies less than a month old
We want to do a study comparing the TGC in 10 newborns without a heart defect to the TGC in 10 newborns with a congenital heart defect To do this we will need one sample of blood the sample we need is 3 cc which is a little more than 12 teaspoon The blood sample for both groups is to be taken from the intravenous catheter IV the child will have placed for surgery The newborns without a heart defect will be children having surgery for a non-cardiac problem
Detailed Description:
Neonates are unique due to maturational differences in their coagulation systems During the first few months of life distinct differences exist between the coagulation system of a neonate and that of an adult including differences between the concentration of coagulation proteins the ability to generate thrombin and the ability to inhibit thrombin once it is formed 1 One important coagulant protein that is quantitatively deficient in the first several months of life is prothrombin In the coagulation cascade prothrombin is converted into thrombin a major regulator of hemostasis In healthy newborns mean prothrombin values are less than 70 of adult mean values 1 and investigators have found that neonatal prothrombin level is directly proportional to the amount of thrombin generated 1 In fact the impaired ability of newborn plasma to generate thrombin in the face of deficient prothrombin has been shown to be similar to adults who are being treated therapeutically with an anticoagulant 2 Therefore low prothrombin levels in neonates have important implications when considering anticoagulant therapy
For neonates with congenital heart disease presenting for cardiac surgery anticoagulation for cardiopulmonary bypass CPB is necessary to prevent clotting as blood comes into contact with the unphysiologic surfaces of the extracorporeal circuit This is achieved by the use of high dose heparin which is used to inhibit the formation and activation of thrombin Since neonatal prothrombin levels are low rendering them unable to generate large amounts of thrombin neonates with congenital heart disease requiring anticoagulation for CPB have historically been considered heparin sensitive 3 However in a recent investigation conducted by this group elevated baseline levels of thrombin production and activity were consistently found in neonates presenting for cardiac surgery 4 Additionally despite routine heparin dosing elevated markers of thrombin production were also found in these neonates during CPB when compared to their adult counterparts 4 Perhaps the assumption that neonates with congenital heart disease are similar to other healthy neonates in their impaired ability to generate thrombin is incorrect Contact activation may occur preoperatively from the presence of indwelling umbilical catheters and central lines or from interventional manipulations in the cardiac catheterization lab and stimulate their coagulation systems to generate more thrombin than anticipated Elevated thrombin levels in neonates presenting for cardiac surgery would consequently have important implications in determining the optimal heparin dose needed to provide adequate anticoagulation for CPB
A technique has been developed to monitor the thrombin generating capacity of plasma 5 A thrombin generation curve TGC can be constructed from a sample of plasma and the area under the TGC called the endogenous thrombin potential ETP is a good indicator of the coagulability of the sample Currently we have found no published data addressing the TGC in the neonatal population Therefore we propose a prospective study between neonates with congenital heart disease presenting for cardiac surgery and other healthy neonates to compare their respective abilities to generate thrombin by measuring TGCs
For neonates with congenital heart disease presenting for cardiac surgery anticoagulation for cardiopulmonary bypass CPB is necessary to prevent clotting as blood comes into contact with the unphysiologic surfaces of the extracorporeal circuit This is achieved by the use of high dose heparin which is used to inhibit the formation and activation of thrombin Since neonatal prothrombin levels are low rendering them unable to generate large amounts of thrombin neonates with congenital heart disease requiring anticoagulation for CPB have historically been considered heparin sensitive 3 However in a recent investigation conducted by this group elevated baseline levels of thrombin production and activity were consistently found in neonates presenting for cardiac surgery 4 Additionally despite routine heparin dosing elevated markers of thrombin production were also found in these neonates during CPB when compared to their adult counterparts 4 Perhaps the assumption that neonates with congenital heart disease are similar to other healthy neonates in their impaired ability to generate thrombin is incorrect Contact activation may occur preoperatively from the presence of indwelling umbilical catheters and central lines or from interventional manipulations in the cardiac catheterization lab and stimulate their coagulation systems to generate more thrombin than anticipated Elevated thrombin levels in neonates presenting for cardiac surgery would consequently have important implications in determining the optimal heparin dose needed to provide adequate anticoagulation for CPB
A technique has been developed to monitor the thrombin generating capacity of plasma 5 A thrombin generation curve TGC can be constructed from a sample of plasma and the area under the TGC called the endogenous thrombin potential ETP is a good indicator of the coagulability of the sample Currently we have found no published data addressing the TGC in the neonatal population Therefore we propose a prospective study between neonates with congenital heart disease presenting for cardiac surgery and other healthy neonates to compare their respective abilities to generate thrombin by measuring TGCs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None