Search

Neonates possess a molecular variant of fibrinogen, known as fetal fibrinogen, characterized by increased sialic acid, a greater negative charge, and decreased activity compared with adults. Despite these differences, adult fibrinogen is used for the treatment of bleeding in neonates, with mixed efficacy. To determine safe and efficacious bleeding protocols for neonates, more information on neonatal fibrin clot formation and the influence of sialic acid on these processes is needed. Here, we examine the influence of sialic acid on neonatal fibrin polymerization. We hypothesized that the increased sialic acid content of neonatal fibrinogen promotes fibrin B:b knob-hole interactions and consequently influences the structure and function of the neonatal fibrin matrix. We explored this hypothesis through analysis of structural properties and knob:hole polymerization dynamics of normal and desialylated neonatal fibrin networks and compared them with those formed with adult fibrinogen. We then characterized normal neonatal fibrin knob:hole interactions by forming neonatal and adult clots with either thrombin or snake-venom thrombin-like enzymes that preferentially cleave fibrinopeptide A or B. Sialic acid content of neonatal fibrinogen was determined to be a key determinant of resulting clot properties. Experiments analyzing knob:hole dynamics indicated that typical neonatal fibrin clots are formed with the release of more fibrinopeptide B and less fibrinopeptide A than adults. After the removal of sialic acid, fibrinopeptide release was roughly equivalent between adults and neonates, indicating the influence of sialic acid on fibrin neonatal fibrin polymerization mechanisms. These results could inform future studies developing neonatal-specific treatments of bleeding.

Neonates possess a molecular variant of fibrinogen, known as fetal fibrinogen, characterized by increased sialic acid, a greater negative charge, and decreased activity compared with adults. Despite these differences, adult fibrinogen is used for the treatment of bleeding in neonates, with mixed efficacy. To determine safe and efficacious bleeding protocols for neonates, more information on neonatal fibrin clot formation and the influence of sialic acid on these processes is needed. Here, we examine the influence of sialic acid on neonatal fibrin polymerization. We hypothesized that the increased sialic acid content of neonatal fibrinogen promotes fibrin B:b knob-hole interactions and consequently influences the structure and function of the neonatal fibrin matrix. We explored this hypothesis through analysis of structural properties and knob:hole polymerization dynamics of normal and desialylated neonatal fibrin networks and compared them with those formed with adult fibrinogen. We then characterized normal neonatal fibrin knob:hole interactions by forming neonatal and adult clots with either thrombin or snake-venom thrombin-like enzymes that preferentially cleave fibrinopeptide A or B. Sialic acid content of neonatal fibrinogen was determined to be a key determinant of resulting clot properties. Experiments analyzing knob:hole dynamics indicated that typical neonatal fibrin clots are formed with the release of more fibrinopeptide B and less fibrinopeptide A than adults. After the removal of sialic acid, fibrinopeptide release was roughly equivalent between adults and neonates, indicating the influence of sialic acid on fibrin neonatal fibrin polymerization mechanisms. These results could inform future studies developing neonatal-specific treatments of bleeding.

Multi-institutional databases and registries have proliferated over the last decade in all specialties of medicine. They may be especially helpful in low-frequency/high-acuity fields such as pediatric and congenital heart diseases. The Society of Thoracic Surgeon’s Congenital Heart Surgery Database (STSCHSD) is the largest single data set for the congenital heart disease population and includes contemporaneous data from over 120 programs in the United States (and several outside of the United States), capturing greater than 98% of the congenital cardiac surgical procedures in the United States. In 2010, the Congenital Cardiac Anesthesia Society partnered with the STSCHSD to incorporate anesthesia-related elements into the data set. Voluntary site participation in the anesthesia data has grown steadily. Currently, over 60 sites performing more than 60% of cardiac bypass procedures in the STSCHSD are submitting anesthesia data annually into the STSCHSD. Anesthesia data include perioperative medication usage, modalities for hemodynamic and neurologic monitoring, blood product, antifibrinolytic and procoagulant use, and anesthesia-related adverse events. This special article provides a descriptive summary of relevant findings to date, reflecting the wide variety in anesthesia practice patterns present among institutions and illustrates the functionality of a multisite registry in pediatric cardiac anesthesia which can be utilized both locally and nationally.

Published ahead of print September 14, 2017.Pediatric cardiac anesthesiology has evolved as a subspecialty of both pediatric and cardiac anesthesiology and is devoted to caring for individuals with congenital heart disease ranging in age from neonates to adults. Training in pediatric cardiac anesthesia is a second-year fellowship with variability in both training duration and content and is not accredited by the Accreditation Council on Graduate Medical Education. Consequently, in this article and based on the Accreditation Council on Graduate Medical Education Milestones Model, an expert panel of the Congenital Cardiac Anesthesia Society, a section of the Society of Pediatric Anesthesiology, defines 18 milestones as competency-based developmental outcomes for training in the pediatric cardiac anesthesia fellowship.

Published ahead of print November 23, 2015

Published ahead of print November 11, 2014.

Recent studies have identified several major qualitative and quantitative differences in important hemostatic proteins between adult and neonatal humans, including the primary coagulation protein fibrinogen.Despite these differences, neonates with post-operative bleeding from procedures requiring cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) are treated with transfusions of adult blood products, namely adult fibrinogen. The effectiveness of such transfusions is inconsistent in neonates and often results in a deficient fibrin matrix structure which may not be sufficient for mitigating bleeding. Our recent studies have also identified differences at the bulk clot level between purified neonatal and adult fibrin clots, including major structural and functional distinctions, which could contribute to these outcomes. Notably, adult fibrinogen degrades slower than neonatal clots, therefore transfusion of adult blood products to neonatal patients could contribute to thrombotic complications. Given the inconsistent results and potential complications from the transfusion of adult blood products to neonatal patients, there is a critical need to better understand the mechanistic differences in hemostatic processes between adults and neonates.

Introduction: Bleeding is a serious complication among neonates undergoing cardiopulmonary bypass (CPB) and it is linked to significant morbidity and mortality. Current standard of care treatment for bleeding after CPB focuses on the transfusion of adult blood products, including platelets and cryoprecipitate. However, prior work by Nellenbach et al. has demonstrated structural differences between neonatal and adult clotting components. Importantly, neonatal and adult fibrin do not fully integrate during clot formation which may contribute to ineffective clot formation and/or increased thrombotic risk following transfusion of adult cryoprecipitate to neonates. There has been increased interest in using human fibrinogen concentrate (HFC) in treating bleeding in the post-CPB neonate; however, HFC has not been validated in this population through evidence-based means. This study analyzed structural and degradation properties of post-CPB clots +/- the ex vivoaddition of HFC and compared structural and degradation properties of post-CPB clots after the in vivotransfusion of HFC versus cryoprecipitate.

Brown: Selsym Biotech, Inc.: Other: Co-Founder and CEO.RiaSTAP (human fibrinogen concentrate) is FDA approved for the treatment of congenital hypofibrinogenemia.