Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.
...
PMID:Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma. 872 36

Cardiopulmonary bypass (CPB) creates a pro-coagulant state by causing platelet activation and inflammation leading to thrombin generation and platelet dysfunction. It is associated with severe derangements in normal homeostasis resulting in both thrombotic and hemorrhagic complications. This derangement is greater in children with congenital heart disease than in adults because of the immaturity of the coagulation system, hemodilution of coagulation factors, hyperreactive platelets, and in some patients, physiologic changes associated with cyanosis. During CPB, an appropriate amount of heparin is given with the goal of minimizing the risk of thrombosis and platelet activation and at the same time reducing the risk of bleeding from over anticoagulation. In young children, this balance is more difficult to achieve because of inherent characteristics of the hemostatic system in these patients. Historically, protocols for heparin dosing and monitoring in children have been adapted from adult protocols without re-validation for children. Extreme hemodilution of coagulation factors and platelets in young children affects the accuracy of anticoagulation monitoring in children. The activated clotting time does not correlate with plasma levels of heparin. In addition, recent studies suggest that children need larger doses of heparin than adults, because they have lower antithrombin levels, and they metabolize heparin more rapidly. Preliminary studies demonstrated that the use of individualized heparin and protamine monitoring and management in children is associated with reduced platelet activation and dysfunction and improved clinical outcomes. However, this review article clearly establishes that further studies are necessary to obtain evidence-based protocols for the proper management of anticoagulation of children undergoing cardiopulmonary bypass.
...
PMID:Management and monitoring of anticoagulation for children undergoing cardiopulmonary bypass in cardiac surgery. 2043 87

Cardiac surgery involving cardiopulmonary bypass imposes a significant pathophysiologic burden on patients. Pediatric patients are especially predisposed to the adverse effects of surgery and bypass on the coagulation system, with resultant bleeding, transfusion, and poor outcomes. These risks accrue to pediatric patients in inverse proportion to their weight and are attributable to hematologic immaturity, coagulation defects associated with congenital heart disease, bypass equipment, and the nature of congenital heart surgery. Standard anticoagulation does not completely inhibit thrombin generation, and continuous consumption of coagulation factor continues throughout bypass. Conventional measurements of anticoagulation during bypass poorly reflect this incomplete anticoagulation, and alternate methods may improve anticoagulant therapy. Emerging therapies for blocking the effects of bypass on the coagulation system hold promise for decreasing bleeding and related complications, and improving outcomes in congenital heart surgery.
...
PMID:Coagulation considerations for infants and children undergoing cardiopulmonary bypass. 2115 25

A primary goal of improving neonatal cardiopulmonary bypass has been making the circuit smaller and reduce the blood contacting surfaces. As bypass circuit size has decreased, bloodless surgery has become possible even in neonates. Since transfusion guidelines are difficult to construct based on existing literature, these technical advances should be taken advantage of in conjunction with an individualized transfusion scheme, based on monitoring of oxygen availability to the tissues. For the majority of neonatal heart operations, several centers have shifted toward normothermic bypass even for complex neonatal surgeries, in order to avoid the adverse effects of hypothermia. Deep hypothermic circulatory arrest is no longer a necessity but an option, and selective antegrade cerebral perfusion has become common practice; however, technical uncertainties with regard to this technique have to be addressed, based on reliable neurologic monitoring. Maintenance of patient-specific heparin concentrations during bypass is another key goal, since neonates have lower baseline antithrombin concentrations and, therefore, a higher risk for inadequate thrombin inhibition and postoperative bleeding. Due to the immaturity of their hemostatic system, the standard coagulation tests alone are inappropriate to guide hemostatic therapy in neonates. The use of indirect heparin concentration assays and global viscoelastic assays in the operating room is likely to represent the optimal strategy, and requires validation in neonates. Monitoring of global and regional indexes of oxygen availability and consumption on bypass have become possible; however, their use in neonates still has outstanding technical issues which should be addressed and hence needs further validation. Due to the immaturity of the neonatal myocardium, single-shot cold cardioplegia solutions are thought to confer the best myocardial protection; their superiority when compared to more conventional modalities, however, remains to be demonstrated.
...
PMID:Recent achievements and future developments in neonatal cardiopulmonary bypass. 3071 61