Tranexamic Acid and Systemic Complement Activation in Traumatic Brain Injury Patients.

Introduction: Traumatic brain injury (TBI) is a leading cause of trauma-related death. A pre-hospital 2-gram bolus of tranexamic acid (TXA) has shown mortality benefit but no reduction in brain bleed size on cross-sectional imaging, suggesting an alternative mechanism may explain its effect. Plasmin activates complement proteins C3 and C5, and complement activation is linked to worse outcomes in animal TBI models.

The Effect of Heterogeneous Definitions of Massive Transfusion on Using Blood Component Thresholds to Predict Futility in Severely Bleeding Trauma Patients.

In the trauma resuscitation literature, there are inconsistent definitions of what constitutes massive transfusion and a unit of blood, complicating the use of transfusion cut-points to declare futility. This is problematic as it can lead to the inefficient use of blood products, further exacerbating current blood product shortages. Previous studies have used various transfusion cut-points per hour to define futility in retrospective analyses but have not accurately defined futility at the bedside due to patient survival even at large rates and volumes of blood transfused.

Coagulation factor XIII: An unrecognized regulator of fibrinolytic phenotypes in trauma-A potential link to protein MENT and cysteine cathepsin degradation of plasminogen.

Background: Trauma-induced coagulopathy (TIC) has distinct fibrinolytic phenotypes based on viscoelastic testing. The underlying mechanisms behind differences in fibrinolytic responses to trauma are unclear. We hypothesized that plasma proteins crosslinked into fibrin clots by the transglutaminase activity of factor XIII (FXIII) may explain tissue-type plasminogen activator (tPA) responsiveness observed in fibrinolysis shutdown.

Change in novel plasmin activated clotting time assay predicts hyperfibrinolysis, massive transfusion, and mortality in trauma in under 3 minutes.

Background: Hyperfibrinolysis after trauma increases mortality, yet rapid identification remains a challenge. Prior work demonstrates liver transplantation is an idealized model of fibrinolysis. Early resource mobilization and antifibrinolytic therapy improves outcomes in trauma, but efficacy is lost with delays in care.

Plasminogen supplementation improves lysis of inflammatory retained traumatic hemothorax.

Introduction: Retained hemothorax (rHTX) occurs when blood persists in the pleural space beyond 72 hours. While initial management involves chest tube placement, failure often necessitates surgical intervention. Intrapleural fibrinolytic therapy (IPFT) with tissue plasminogen activator (tPA)/DNase is a nonoperative alternative, but failure rates remain high (>20%).

Hyperfibrinolysis is Associated with Complement Activation Following Trauma.

Complement is activated after trauma, but the activation mechanism is unknown. Plasmin can directly activate C3 and C5, and four distinct fibrinolytic phenotypes have now been recognized after injury-hyperfibrinolysis, fibrinolysis shutdown, hypofibrinolysis, and nonpathologic/physiologic.We set out to investigate whether a relationship between complement activation and fibrinolysis was present in adult trauma patients ( = 56).

A Novel Fibrinolysis Resistance Capacity Assay Can Detect Fibrinolytic Phenotypes in Trauma Patients.

Background:  To evaluate residual fibrinolysis resistance activity (FRA) in plasma, a detergent-modified plasma clot lysis assay time (dPCLT) was established in which α2-antiplasmin (A2AP) and plasminogen activator inhibitor type 1 (PAI-1) are inactivated without impacting protease activity. We applied this novel assay to severely injured trauma patients' plasma.

Material And Methods:  Tissue-type plasminogen activator (tPA)-induced plasma clot lysis assays were conducted after detergents- (dPCLT) or vehicle- (sPCLT) treatment, and time to 50% clot lysis was measured ("transition midpoint", T ).

The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured.

Background: Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.

Methods: Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval.

Erratum to 'Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress' [Research and Practice in Thrombosis and Haemostasis Volume 8, Issue 4, May 2024, 102432].

[This corrects the article DOI: 10.1016/j.rpth.

Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma.

Background: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.

Methods: Retrospective chart review was performed.

Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation.

Background: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT).

Versatile, in-line optical oxygen tension sensors for continuous monitoring during kidney perfusion.

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices.

Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field.

Neutrophil-Mediated Inflammatory Plasminogen Degradation, Rather Than High Plasminogen-Activator Inhibitor-1, May Underly Failures and Inefficiencies of Intrapleural Fibrinolysis.

Background: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation.

Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.

Differentiating Pathologic from Physiologic Fibrinolysis: Not as Simple as Conventional Thrombelastography.

Background: Conventional rapid thrombelastography (rTEG) cannot differentiate fibrinolysis shutdown from hypofibrinolysis, as both of these patient populations have low fibrinolytic activity. Tissue plasminogen activator (tPA) TEG can identify depletion of fibrinolytic inhibitors, and its use in combination with rTEG has the potential to differentiate all 3 pathologic fibrinolytic phenotypes after trauma. We hypothesize tPA-TEG and rTEG in combination can further stratify fibrinolysis phenotypes postinjury to better stratify risk for mortality.

Combination of aspirin and rosuvastatin for reduction of venous thromboembolism in severely injured patients: a double-blind, placebo-controlled, pragmatic randomized phase II clinical trial (The STAT Trial).

Introduction: Venous thromboembolism (VTE) remains a significant source of postinjury morbidity and mortality. Beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (rosuvastatin) significantly reduced pathologic clotting events in healthy populations in a prior trial. Furthermore, acetylsalicylic acid (ASA) has been shown to be noninferior to prophylactic heparinoids for VTE prevention following orthopedic surgery.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported.

Development and in-vivo validation of a portable phosphorescence lifetime-based fiber-optic oxygen sensor.

Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e.

Early predictors of prolonged intensive care utilization following liver transplantation.

Introduction: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU.

Methods: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1.