Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.

Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity.

Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium.

Background: Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM.

Effect of Unfractionated Heparin Dose on Complement Activation and Selected Extracellular Vesicle Populations during Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation.

Hyperfibrinolysis: potential guidance for decision-making to avoid futile extracorporeal cardiopulmonary resuscitation.

Out-of-hospital cardiac arrest (OHCA) is associated with very poor outcomes. Extracorporeal cardiopulmonary resuscitation (eCPR) for selected patients is a potential therapeutic option for refractory cardiac arrest. However, randomised controlled studies applying eCPR after refractory OHCA have demonstrated conflicting results regarding survival and good functional neurological outcomes.

Development of a Paper-based Hematocrit Test and a Lateral Flow Assay to Detect Critical Fibrinogen Concentrations Using a Bottom-Up Pyramid Workflow Approach.

Fibrinogen is a coagulation factor in human blood and the first one to reach critical levels in major bleeding. Hypofibrinogenemia (a too low fibrinogen concentration in blood) poses great challenges to first responders, clinicians, and healthcare providers since it represents a risk factor for exsanguination and massive transfusion requirements. Thus, the rapid assessment of the fibrinogen concentration at the point of care has gained considerable importance in preventing and managing major blood loss.

Stress hyperglycaemia following trauma - a survival benefit or an outcome detriment?

Purpose Of Review: Stress hyperglycaemia occur often in critically injured patients. To gain new consideration about it, this review compile current as well as known immunological and biochemical findings about causes and emergence.

Recent Findings: Glucose is the preferred energy substrate for fending immune cells, reparative tissue and the cardiovascular system following trauma.

Comparison of Two Viscoelastic Testing Devices in a Parturient Population.

: Viscoelastic hemostatic assays (VHAs) have become an integral diagnostic tool in guiding hemostatic therapy, offering new opportunities in personalized hemostatic resuscitation. This study aims to assess the interchangeability of ClotPro® and ROTEM® delta in the unique context of parturient women. : Blood samples from 217 parturient women were collected at three timepoints.

Circulating endothelial extracellular vesicle signatures correspond with ICU requirement: an exploratory study in COVID-19 patients.

Extracellular vesicles (EVs) represent nanometer-sized, subcellular spheres, that are released from almost any cell type and carry a wide variety of biologically relevant cargo. In severe cases of coronavirus disease 2019 (COVID-19) and other states of systemic pro-inflammatory activation, EVs, and their cargo can serve as conveyors and indicators for disease severity and progression. This information may help distinguish individuals with a less severe manifestation of the disease from patients who exhibit severe acute respiratory distress syndrome (ARDS) and require intensive care measures.

Point-of-care, goal-directed management of bleeding in trauma patients.

Purpose Of Review: The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC).

Recent Findings: Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies.

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study.

Purpose: Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission.

Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis.

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases.

Factor XIII Measurement and Substitution in Trauma Patients after Admission to an Intensive Care Unit.

Trauma patients admitted to an intensive care unit (ICU) may potentially experience a deficiency of coagulation factor thirteen (FXIII). In this retrospective cohort study conducted at a specialized trauma center, ICU patients were studied to determine the dependency of FXIII activity levels on clinical course and substitution with blood and coagulation products. A total of 189 patients with a median injury severity score (ISS) of 25 (16−36, IQR) were included.

Role of DOAC plasma concentration on perioperative blood loss and transfusion requirements in patients with hip fractures.

Background: There is an ever-increasing number of hip fracture (HF) patients on direct oral anticoagulants (DOAC). The impact of DOAC plasma level prior to HF surgery on perioperative blood loss and transfusion requirements has not been investigated so far.

Materials And Methods: In this retrospective study of HF patients on DOACs admitted to the AUVA Trauma Center Salzburg between February 2015 and December 2021.

Operability of a Resonance-Based Viscoelastic Haemostatic Analyzer in the High-Vibration Environment of Air Medical Transport.

Trauma and bleeding are associated with a high mortality, and most of these deaths occur early after injury. Viscoelastic haemostatic tests have gained increasing importance in goal-directed transfusion and bleeding management. A new generation of small-sized and thus portable ultrasound-based viscoelastic analysers have been introduced in clinical practice.

Multiplate Platelet Function Testing upon Emergency Room Admission Fails to Provide Useful Information in Major Trauma Patients Not on Platelet Inhibitors.

Platelet dysfunction is a suggested driver of trauma-induced coagulopathy. However, there is still a paucity of data regarding the impact of injury pattern on platelet function and the association of platelet dysfunction on transfusion requirements and mortality. In this retrospective cohort study, patients were grouped into those with isolated severe traumatic brain injury (TBI group), those with major trauma without TBI (MT group), and a combination of both major trauma and traumatic brain injury (MT + TBI group).

Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis.

Background: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.

Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients.

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated.

High Interleukin-6 Plasma Concentration upon Admission Is Predictive of Massive Transfusion in Severely Injured Patients.

Severe bleeding remains a prominent cause of early in-hospital mortality in major trauma patients. Thus, prompt prediction of patients at risk of massive transfusion (MT) is crucial. We investigated the ability of the inflammatory marker interleukin (IL)-6 to forecast MT in severely injured trauma patients.

Fluorescence-Based Nanoparticle Tracking Analysis and Flow Cytometry for Characterization of Endothelial Extracellular Vesicle Release.

As extracellular vesicles (EVs) have become a prominent topic in life sciences, a growing number of studies are published on a regular basis addressing their biological relevance and possible applications. Nevertheless, the fundamental question of the true vesicular nature as well as possible influences on the EV secretion behavior have often been not adequately addressed. Furthermore, research regarding endothelial cell-derived EVs (EndoEVs) often focused on the large vesicular fractions comprising of microvesicles (MV) and apoptotic bodies.

A prospective observational study of the rapid detection of clinically-relevant plasma direct oral anticoagulant levels following acute traumatic injury.

In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® analyser, we assessed two novel viscoelastic tests for detection of clinically-relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors.

In vitro effects of 635 nm photobiomodulation under hypoxia/reoxygenation culture conditions.

Photobiomodulation (PBM), especially in the red wavelength range, has been demonstrated to be an effective treatment option for superficial and chronic wounds. However, ischemia and subsequent reperfusion can further challenge wound healing. Therefore, we investigated the effect of pulsed red LED light at 635 nm on cellular function in an in-vitro model of hypoxia/reoxygenation (H/R) challenge.

Comparison of fresh frozen plasma vs. coagulation factor concentrates for reconstitution of blood: An in vitro study.

Background: Many trauma centres have adopted the administration of fixed ratios of packed red blood cells (PRBCs), platelet concentrates and fresh frozen plasma (FFP) for bleeding patients. However, the haemostatic efficacy of this concept is not well proven.

Objective: Our objective was to characterise the haemostatic profile of different ratios (2 : 1 : 1, 1 : 1 : 1 and 1 : 1 : 2) of PRBCs, platelet concentrates and FFP in comparison with coagulation factor concentrates (fibrinogen and/or prothrombin complex concentrate).

Idarucizumab in major trauma patients: a single centre real life experience.

Introduction: Trauma care providers are facing an increasing number of elderly patients on direct oral anticoagulants prior to injury. For dabigatran etexilate (DAB), the specific antagonist idarucizumab (IDA) has been approved since 2015 as a reversal agent. However, only limited data regarding the use of IDA in trauma patients are available.