Elevated preoperative von Willebrand factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease.

Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. Objectives To describe perioperative changes to VWF, ADAMTS-13 and NETosis, and evaluate clinical and biochemical associations with postoperative thrombosis. Methods Neonates and infants undergoing palliation or definitive surgical repair of congenital heart malformations were recruited (n = 133). Preoperative and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. Results We identified significant postoperative increases in VWF activity, VWF level, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL-1 , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg-1 , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital heart malformations are exposed to high levels of VWF with diminished or minimal change to ADAMTS-13 in the immediate postoperative period. Elevated preoperative VWF activity is associated with postoperative thrombosis in pediatric congenital heart disease.

Early thromboelastometry variables predict maximum clot firmness in children undergoing cardiac and non-cardiac surgery.

BACKGROUND: Early clot amplitudes measured on thromboelastometry (ROTEM®) predict maximum clot firmness (MCF) in adults. In this multicentre, retrospective study, we aimed to confirm the suspected relationship between early ROTEM® variables and MCF, in children undergoing cardiac or non-cardiac surgery. METHODS: 4762 ROTEM® tests (e.g. EXTEM, INTEM, FIBTEM, APTEM, and HEPTEM) performed in children undergoing cardiac or non-cardiac surgery at three University hospitals between January 2011 and June 2014 were reviewed. To assess the correlation between clot amplitudes measured after 5, 10 and 15 min and MCF, each variable was compared with the corresponding MCF by calculating Spearman's correlation coefficient. RESULTS: For the EXTEM® test, we observed that amplitude measured after 5 min (A5: r=0.91, P<0.001), 10 min (A10: r=0.95, P<0.001) and 15 min (A15: r=0.96, P<0.001) were strongly correlated to MCF. The same correlations were observed for INTEM® test (A5: r=0.93, P<0.001; A10: r=0.97, P<0.001; A15: r=0.97, P<0.001), and FIBTEM® test (A5: r=0.93, P<0.001; A10: r=0.94, P<0.001; A15: r=0.96, P<0.001). In addition, the amplitudes measured after five, 10 and 15 min were also strongly correlated with MCF in the APTEM® and the HEPTEM® tests. Receiver operating characteristics (ROC) analysis confirmed that A5, A10, A15 strongly predicted decreased MCF on all ROTEM® tests. CONCLUSIONS: This study confirmed that early values of clot amplitudes measured as soon as five, 10 or 15 min after clotting time could be used to predict maximum clot firmness in all ROTEM® tests.

[Efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of post-partum haemorrhage: a systematic review with meta-analysis]. / Efficacité et sécurité de l'acide tranexamique en prévention et/ou en traitement de l'hémorragie du post-partum : une revue systématique de la littérature avec méta-analyse.

OBJECTIVE(S): Assess the efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of postpartum haemorrhage. STUDY DESIGN: Systematic review with meta-analysis. MATERIAL AND METHODS: Systematic review of the literature with the aim of identifying prospective, randomised, controlled trials that assessed the effect of tranexamic acid on peripartum blood loss and transfusion requirement in three clinical contexts: (i) prevention of post-partum haemorrhage in case of elective caesarean section, (ii) prevention of post-partum haemorrhage in case of vaginal delivery, (iii) treatment of post-partum haemorrhage. RESULTS: Prophylactic administration of tranexamic acid reduced blood loss (mean difference for intraoperative blood loss: -177.9mL, IC 95%: -189.51 to -166.35, total blood loss: -183.94, IC 95%: -198.29 to -169.60), and the incidence of severe post-partum haemorrhage (OR: 0.49, IC 95%: 0.33 to 0.74). None of the published trials assessed the effect of tranexamic acid on blood products administration or transfusion requirement. Only one study assessed and reported the efficacy of tranexamic acid when administered as a treatment for postpartum haemorrhage. A significant reduction in blood loss was reported within 30 minutes after randomisation (P=0.03) and confirmed after 6 hours (median: 170mL (58-323) vs 221mL (110-543), P=0.04). None of the included studies adequately studied the incidence of side effects after tranexamic acid administration. CONCLUSION: Although tranexamic acid administration seemed to significantly reduce blood loss and the incidence of severe post-partum haemorrhage, further prospective trials are needed to confirm the efficacy and safety of tranexamic administration in the treatment of postpartum haemorrhage. Those studies should assess the pharmacokinetic profile and the safety of this drug in pregnant women.

Multivariate model for predicting postoperative blood loss in children undergoing cardiac surgery: a preliminary study.

BACKGROUND: Postoperative bleeding and blood product transfusion increase morbidity, mortality, and costs after cardiac surgery. However, factors that could accurately predict bleeding have not been well studied in children undergoing cardiac surgery. This study aims at determining factors that could be used to predict postoperative bleeding in this paediatric population. METHODS: We included 182 children undergoing congenital heart surgery. Significant bleeding was defined as a blood loss that exceeds 10% of total blood volume within the first 6 postoperative hours. Univariate and multivariate logistic regression analyses were performed to determine variables independently associated with bleeding. These variables were used to calculate a probability for each individual child to develop postoperative bleeding. RESULTS: According to the definition of bleeding, 44 patients were included into the 'bleeder' group and 138 into the 'non-bleeder' group. Factors independently associated with postoperative bleeding were preoperative body weight, the presence of a cyanotic disease, and the time required for wound closure. Based on these three parameters, we calculated the probability of bleeding and found a significant relationship with postoperative bleeding. Finally, a calculated probability of 0.59 can predict significant postoperative blood loss with a sensitivity of 84% and a specificity of 64%. CONCLUSIONS: This study shows that preoperative body weight, cyanotic disease, and wound closure duration are best predictors of bleeding in the paediatric population after cardiac surgery. The combination of these three factors could be used at the end of the surgery to estimate the probability of postoperative bleeding.

A systematic review of antifibrinolytics and massive injury.

Every year, more than a million people die as a result of trauma. This huge mortality could be partially explained by the development of an acute traumatic coagulopathy, present in a large part of all major trauma patients, soon after injury, which contributes to ongoing hemorrhage. The coagulopathy induced by trauma is independently associated with mortality, increased transfusion requirements, multiple organ dysfunction, infections, increased intensive care unit (ICU) length of stay, and costs. The pathophysiological mechanisms implicated in this acute traumatic coagulopathy are complexes and lead to generate a vicious circle leading to the activation of different pathways: thrombin generation, plasmin generation, inflammation activation. All of these processes will impair the balance between clot formation and clot lysis, with an increased tendency of hyperfibrinolysis. In 2010, the CRASH-2 trial demonstrated that tranexamic acid (TXA) administration was associated with a reduction in all cause mortality (14.5% vs. 16%, P=0.0035), including the risk of death due to bleeding (4.9% vs. 5.8%, P=0.0077), without an increase in fatal or non-fatal vascular occlusive events. Finally, the CRASH-3 trial is now recruiting patients with traumatic brain injury without extracranial bleeding. This study aims at determining the safety and efficacy of TXA administration in this particular setting. Our experience from the cardiac surgery setting highlighted a dose-dependent increased seizure incidence associated with the administration of TXA. For this reason, further studies are needed to better define the "optimal" dose scheme based on pharmacokinetic and pharmacodynamic studies.

Ketamine has no effect on bispectral index during stable propofol-remifentanil anaesthesia.

BACKGROUND: Ketamine 0.15-1 mg kg(-1) decreases postoperative morphine consumption, but 0.5 mg kg(-1) is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents. The purpose of our investigation was to study the effect of ketamine 0.2 mg kg(-1) administered over a 5 min period on the BIS during stable target-controlled infusion (TCI) propofol-remifentanil general anaesthesia. METHODS: Thirty ASA I or II patients undergoing abdominal laparoscopic surgery were included in this double-blind, randomized study. Anaesthesia was induced and maintained with a TCI of propofol and remifentanil. After 5 min of steady-state anaesthesia (BIS at 40) without surgical stimulation, patients received either an infusion of ketamine 0.2 mg kg(-1) or normal saline. The test drug was infused over 5 min. Standard parameters and BIS values were recorded every minute until 15 min post-infusion. RESULTS: The baseline mean (sd) value for the BIS was 37 (6.5) for the ketamine group and 39 (8.2) for the placebo group. The highest mean BIS value during the recording period was 41.5 (8.7) for the ketamine group and 40.1 (8.9) for the placebo group. BIS values were not statistically different between the groups (P=0.62); there was no significant change over time (P=0.65) with no group-time interaction (P=0.55). CONCLUSIONS: Under stable propofol and remifentanil TCI anaesthesia, a slow bolus infusion of ketamine 0.2 mg kg(-1) administered over a 5 min period did not increase the BIS value over the next 15 min.