Hemostatic Profiles of Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement Versus Percutaneous Coronary Intervention.

Guidelines for transcatheter aortic valve replacement (TAVR) antithrombotic prophylaxis are extrapolated predominantly from percutaneous coronary intervention (PCI) data. Here, we examined temporal coagulation changes occurring in the early perioperative period to determine the pathobiologic validity of this supposition. This was a prospective observational study of consecutive patients who underwent transfemoral TAVR (n = 27), PCI (n = 12), or surgical aortic valve replacement (SAVR) requiring cardiopulmonary bypass and cross-clamping (n = 12). Blood samples were taken at 4 time points: T1 (baseline), after general anesthesia or sedation; T2, after heparin administration; T3, at the end of the procedure; and T4, 6 hours after the procedure. The samples were assessed concurrently using standard laboratory coagulation tests and viscoelastic tests of whole blood clotting, including the latest generation thromboelastometry (ROTEM sigma) and thromboelastometry (TEG 6s). Patients in the TAVR cohort were older and a had lower baseline hemoglobin level than patients in the PCI and SAVR cohorts. The baseline platelet function was similar between the TAVR and PCI cohorts and impaired in the SAVR cohort Figure S1. The baseline hemostatic measures were comparable among cohorts. Regarding the per-patient change from baseline, the TAVR cohort showed an overall more prothrombotic state than the other cohorts, with the most marked differences from the SAVR cohort after intraoperative heparin administration and from the PCI cohorts 6 hours after the procedure. In addition, the ROTEM and TEG parameters were well correlated but not interchangeable. In conclusion, patients who underwent TAVR have a more prothrombotic hemostatic profile than PCI and SAVR patients. These findings question the current guidelines that extrapolate antithrombotic regimens from PCI to TAVR settings.

Fresh frozen plasma and platelet concentrate storage duration not associated with in hospital mortality risk.

BACKGROUND AND OBJECTIVES: To date, the effects of FFP and PC storage duration on mortality have only been studied in a few studies in limited patient subpopulations. The aim of the current study was to determine whether FFP and PC storage duration is associated with increased in hospital mortality risk across cardiac surgery, acute medicine, ICU and orthopaedic surgery patients. MATERIALS AND METHODS: Two-stage individual patient data meta-analyses were performed to determine the effects of FFP and PC storage duration on in hospital mortality. Preset random effects models were used to determine pooled unadjusted and adjusted (adjusted for age, gender and units of product transfused) effect estimates. RESULTS: The FFP storage duration analysis included 3625 patients across four studies. No significant association was observed between duration of storage and in hospital mortality in unadjusted analysis, but after adjusting for patient age, gender and units of product a small increased risk of in hospital mortality was observed for each additional month of storage (OR: 1·05, 95% CI: 1·01-1·08). This effect was no longer statistically significant when donor ABO blood group was incorporated into the random effects model on post hoc analyses. A total of 547 patients across five studies were incorporated in the PC storage duration analysis. No association was observed between PC storage duration and odds of in hospital morality (adjusted OR: 0·94, 95% CI: 0·79-1·11). CONCLUSIONS: There is insufficient evidence to support shortening FFP or PC shelf life based on in hospital mortality.

Corrigendum: Sepsis: Changing Definitions, Unchanging Treatment.

[This corrects the article DOI: 10.3389/fped.2018.00425.].

Platelet Storage Lesions: What More Do We Know Now?

Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage. This article will review advancements in clinical and mechanistic PSL research. In brief, exposure to artificial surfaces and high centrifugation forces during PC preparation initiate PSLs by causing platelet activation, fragmentation, and biochemical release. During room temperature storage, enhanced glycolysis and reduced mitochondrial function lead to glucose depletion, lactate accumulation, and product acidification. Impaired adenosine triphosphate generation reduces platelet capacity to perform energetically demanding processes such as hypotonic stress responses and activation/aggregation. Storage-induced alterations in platelet surface proteins such as thrombin receptors and glycoproteins decrease platelet aggregation. During storage, there is an accumulation of immunoactive proteins such as leukocyte-derive cytokines (tumor necrosis factor α, interleukin (IL) 1α, IL-6, IL-8) and soluble CD40 ligand which can participate in transfusion-related acute lung injury and nonhemolytic transfusion reactions. Storage-induced microparticles have been linked to enhanced platelet aggregation and immune system modulation. Clinically, stored PCs have been correlated with reduced corrected count increment, posttransfusion platelet recovery, and survival across multiple meta-analyses. Fresh PC transfusions have been associated with superior platelet function in vivo; however, these differences were abrogated after a period of circulation. There is currently insufficient evidence to discern the effect of PSLs on transfusion safety. Various bag and storage media changes have been proposed to reduce glycolysis and platelet activation during room temperature storage. Moreover, cryopreservation and cold storage have been proposed as potential methods to prolong PC shelf life by reducing platelet metabolism and bacterial proliferation. However, further work is required to elucidate and manage the PSLs specific to these storage protocols before its implementation in blood banks.

Sepsis: Changing Definitions, Unchanging Treatment.

The recently revised Sepsis-3 definitions were based on criteria that were derived and validated in adult patient databases from high income countries. Both sepsis and septic shock continue to account for a substantial proportion of mortality globally, especially amongst children in low-and-middle income country settings. It is therefore urgent to develop and validate standardized criteria for sepsis that can be applied to pediatric populations in different settings, including in- and outside intensive care, both in high- and low/middle- income countries. This will be a pre-requisite to evaluate the impact of sepsis treatment strategies to improve clinical outcomes.

Effects of packed red blood cell storage duration on post-transfusion clinical outcomes: a meta-analysis and systematic review.

PURPOSE: There is substantial conjecture regarding the clinical significance of packed red blood cell (PRBC) changes that occur during in vitro storage. Here, we present a meta- and systematic analysis of adult studies published between 1994 and 2015 with the aim of updating existing quantitative reviews and providing a comprehensive cover of the six most commonly studied outcomes-mortality, infection, renal dysfunction, multiple organ dysfunction syndrome (MODS), thrombotic complications and prolonged hospital length of stay. METHODS: Computerised searches of Pubmed and EMBASE identified publications that reported target outcomes and PRBC storage duration prior to transfusion. Bibliographies of relevant literature were manually searched to incorporate missed studies. Randomised controlled trial (RCT) data was meta-analysed using a random effects model with Cochrane Collaboration Review Manager (RevMan) version 5.1 software. Observational investigations were systematically reviewed. RESULTS: Sixty-four papers were selected covering 462,581 patients with the majority of studies being observational in nature. Meta-analysis of eight RCTs demonstrated a trend towards decreased mortality with stored PRBC transfusion; albeit this effect was not statistically significant (OR 0.91, 95 % CI 0.78-1.05, p = 0.20). In a small subset of intensive care unit (ICU), cardiac surgery and trauma patients; observational studies suggested that prolonged storage may be correlated with increased mortality. Trauma and cardiac surgery patients appeared to be most susceptible to the potential infectious complications of stored PRBCs. Stored PRBCs were unlikely to affect thrombotic complications or hospital length of stay. There were inadequate data to determine whether stored PRBCs had clinically relevant effects on renal dysfunction and MODS. CONCLUSION: Although literature presents a concerning picture of potential storage complications, current findings are too inconsistent to drive changes in clinical practice. Results from current RCTs will likely play a role in PRBC age guidelines for cardiac surgery and ICU patients. However, these studies may be less efficacious at detecting small effects that are limited to specific subpopulations.

Oxidative stress during extracorporeal circulation.

There is an increased oxidative stress response in patients having cardiac surgery, haemodialysis or extracorporeal membrane oxygenation that is related to poorer outcomes and increased mortality. Exposure of the patients' blood to the artificial surfaces of these extracorporeal devices, coupled with inflammatory responses, hyperoxia and the pathophysiological aspects of the underlying illness itself, all contribute to this oxidative stress response. Oxidative stress occurs when there is a disruption of redox signalling and loss of control of redox balance. Ongoing oxidative stress occurring during extracorporeal circulation (ECC) results in damage to lipids, proteins and DNA and contributes to morbidity and mortality. This review discusses reactive species generation and the potential clinical consequences of oxidative stress during ECC as well as provides an overview of some current antioxidant compounds that are available to potentially mitigate the oxidative stress response.

The role of echocardiography in the management of patients supported by extracorporeal membrane oxygenation.

Extracorporeal life support can be viewed as a spectrum of modalities based on modifications of a cardiopulmonary bypass circuit to provide cardiac and respiratory support, which can be used for extended periods, from hours to several weeks. Extracorporeal membrane oxygenation (ECMO) is among the most frequently used forms of extracorporeal life support. It can be configured for venovenous blood flow, to provide adequate oxygenation and carbon dioxide removal in isolated refractory respiratory failure, or in a venoarterial configuration, when support is required for cardiac and/or respiratory failure. Echocardiography plays a fundamental role throughout the entire journey of a patient supported on ECMO. It provides information that assists in patient selection, guides the insertion and placement of cannulas, monitors progress, detects complications, and helps in determining cardiac recovery and the weaning of ECMO support. Although there are extensive published data regarding ECMO, particularly in the pediatric population, there is a paucity of data outlining the role of echocardiography in guiding the management of adult patients supported by ECMO. ECMO is likely to become an increasingly used form of cardiorespiratory support within the critical care setting. Hence, clinicians and sonographers who work within echocardiography departments at institutions with ECMO programs require specific skills to image these patients.