Fibrinogen and FXIII dose response effects on albumin-induced coagulopathy.

Objectives. Natural colloid albumin induces a lesser degree of dilutional coagulopathy than synthetic colloids. Fibrinogen concentrate has emerged as a promising strategy to treat coagulopathy, and factor XIII (FXIII) works synergistically with fibrinogen to correct coagulopathy following haemodilution with crystalloids. Our objectives were to examine the ability of fibrinogen and FXIII concentrates to reverse albumin-induced dilutional coagulopathy. Methods. High and low concentrations of both fibrinogen and FXIII were used to reverse coagulopathy induced by 1:1 dilution in vitro with 5% albumin of blood samples from healthy volunteers, monitored by rotational thromboelastometry (ROTEM(®)). Results. Haemodilution with albumin significantly attenuated EXTEM maximum clot firmness (MCF), alpha angle (AA), clotting time (CT) and clot formation time (CFT), and FIBTEM MCF (p < 0.001). Following haemodilution, both doses of fibrinogen significantly corrected all ROTEM parameters (p ≤ 0.02), except the lower dose did not correct AA. Compared to the lower dose, the higher dose of fibrinogen significantly improved FIBTEM MCF and EXTEM MCF, AA and CFT (p < 0.001). The lower dose of FXIII did not significantly correct any of the ROTEM parameters, and the high dose only improved EXTEM CT (p = 0.004). All combinations of high/low concentrations of fibrinogen/FXIII significantly improved all ROTEM parameters examined (p ≤ 0.001). Fibrinogen concentration generally had a greater effect on each parameter than did FXIII concentration; the best correction of ROTEM parameters was achieved with high-dose fibrinogen concentrate and either low- or high-dose FXIII. Conclusions. Fibrinogen concentrate successfully corrected initiation, propagation and clot firmness deficits induced by haemodilution with albumin, and FXIII synergistically improved fibrin-based clot strength

Albumin-induced coagulopathy is less severe and more effectively reversed with fibrinogen concentrate than is synthetic colloid-induced coagulopathy.

Background. Synthetic colloids cause dilutional coagulopathy. The aims of our study were to determine whether the natural colloid albumin induces a lesser degree of coagulopathy compared to synthetic colloids, and the comparative effectiveness of fibrinogen concentrate to reverse coagulopathy following dilution with these solutions. Methods. Coagulation was assessed with rotational thrombelastometry after stimulation with tissue factor (EXTEM) and in the presence of a platelet inhibitor (FIBTEM). With EXTEM, clotting time (CT), clot formation time CFT), alpha angle (AA) and maximum clot firmness (MCF) were recorded. With FIBTEM, only MCF was recorded. These parameters were assessed ex vivo in blood from 10 healthy volunteers; diluted 1:1 with either saline, Ringer's acetate, buffered/unbuffered hydroxyethyl starch, buffered/unbuffered dextran (synthetic colloids) or 5% albumin. Samples were analyzed before/after addition of fibrinogen concentrate. Results. FIBTEM MCF decreased significantly upon dilution (> 50% reduced) with all colloid solutions (p ≤ 0.02), although a significantly greater coagulopathic effect was seen for samples diluted with synthetic colloids versus albumin (p ≤ 0.001). A significant reduction in the platelet component of clot strength (EXTEM MCF - FIBTEM MCF) was seen for samples diluted with synthetic colloids (p < 0.001) but not albumin (p = 0.10). Following addition of fibrinogen, FIBTEM MCF, EXTEM MCF and AA were significantly higher, and CFT was significantly shorter in samples diluted with albumin versus those treated with synthetic colloids (p ≤ 0.001). Conclusion. Hemodilution using albumin induced a lesser degree of coagulopathy compared with the synthetic colloids. In addition, albumin-induced coagulopathy was more effectively reversed following addition of fibrinogen concentrate compared with coagulopathy induced by synthetic colloids

Place and Destination Branding: A Review and Conceptual Mapping of the Domain

Although there is increasing interest in place and destination branding, the inter‐disciplinary nature of the field poses challenges for the development of a coherent knowledge base. With a view to informing both research and practice, this article presents a systematic review combining place and destination branding, identifying and defining its core themes, and developing a conceptual map of the inter‐play between them. The following key themes are identified: general, brand identity, image and personality, politics, heritage, communication/media, country‐of‐ origin, and designscape and infrastructure. The article concludes with an agenda for further research including the need for research on specific themes across a wider range of place entities

Detection of in-utero ethanol exposure via EtG and EtS analysis in umbilical cord and placenta

Alcohol exposure during pregnancy constitutes one of the leading preventable causes of birth defects, mental retardation and neurodevelopmental disorders in exposed children. According to the 2016 National Survey on Drug Use and Health, alcohol was the second most prevalent substance (8.3%) after tobacco (10%), being this alcohol prevalence higher among 26-44 years old pregnant women than in the 18-25 years old group (9.1 vs 6.5%) (Center for Behavioral Health Statistics and Quality, 2017). The ethanol marker ethyl glucuronide (EtG) has proven to be a specific long-term marker of ethanol in-utero exposure in meconium; however, currently there are scarce or no data about EtG and ethyl sulfate (EtS) in umbilical cord and placenta. These tissues are alternative matrices to meconium that offer critical advantages; as they are always available at birth, their collection is noninvasive and easy, and they are considered waste products. We developed a method for the determination of EtG and EtS in 0.1 g of umbilical cord and placenta, achieving a limit of quantification of 5 ng/g in umbilical cord and 10 ng/g in placenta. Tissues were homogenized in methanol and the analytes of interest were extracted using weak anion exchange solid phase extraction and analyzed by liquid chromatography tandem mass spectrometry (LC-MSMS), in negative mode, monitoring 2 transitions per analyte. The methods were applied to 59 authentic umbilical cord and placenta samples from newborns whose meconium samples were positive for EtG (EtG \u3e 5 ng/g). EtG and/or EtS were detected in 25 umbilical cord samples with ranges of 4.4-528.5 ng/g and 4.3-39 ng/g, respectively, and in 8 placenta samples with ranges of 26.5-266.5 and 11-24.3 ng/g, respectively. EtG and EtS showed a homogenous distribution throughout umbilical cord tissue (n=5). To date, this is the first method to investigate both minor metabolites of ethanol in term umbilical cord and placenta samples for prenatal ethanol exposure