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.

Antigen-Fc fusion therapy reduces severity of a model of pemphigus vulgaris without systemic immunosuppression.

Pemphigus vulgaris is a B cell-mediated autoimmune disease characterized by autoantibodies targeting desmoglein-3 (Dsg3), a critical adhesion molecule in epithelial tissues. Current treatments rely on broad immunosuppression, highlighting the need for more targeted therapeutic approaches in pemphigus vulgaris and other autoantibody-driven disorders. We engineered a therapeutic fusion protein consisting of the pathogenic domains of Dsg3 linked to either human immunoglobulin G1 (IgG1) or mouse IgG2a (Dsg3-Fc).

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%).

The Joint Trauma System: A critical lifeline facing an uncertain future.

The Joint Trauma System (JTS) has become a cornerstone of modern trauma care, revolutionizing battlefield treatment and saving countless lives through standardized, evidence-based protocols. Its development and success are rooted in lessons learned from the wars in Iraq and Afghanistan, where fragmented systems were transformed into cohesive, high-performing networks. The JTS has influenced not only military but also civilian trauma care, fostering a symbiotic relationship that advances innovation across both sectors.

Pleural Space Diseases and Their Management: What is the Role of Intrapleural Fibrinolytic Therapy?

Pleural space diseases are a significant cause of morbidity in the United States with a reported 25% mortality rate within a year of diagnosis. Pleural space diseases, including intrapleural infections, retained hemothorax (RH), and malignant pleural effusions (MPE), often indicate advanced disease. Despite options like video-assisted thoracoscopy (VATS), tube thoracostomy, and intrapleural fibrinolytic therapy (IPFT), treatment remains a significant clinical challenge.

Is Resuscitative Endovascular Balloon Occlusion of the Aorta contraindicated in the elderly? An analysis of the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry.

Introduction: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as a critical tool in trauma management, particularly for elderly patients. However, its application in this population is often debated because of concerns over potential complications. This study evaluates the outcomes of REBOA compared with resuscitative thoracotomy (RT) in trauma patients 65 years or older with indications for aortic occlusion.

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).

High-dimensional analysis of injured patients reveals distinct circulating proteomic profiles in plasma vs. whole blood resuscitation.

Early blood product resuscitation is often essential for optimal trauma care. However, the effects of different products on the underlying trauma-induced coagulopathy and immune dysfunction are not well described. Here, we use high-dimensional analysis and causal modeling in a longitudinal study to explore the circulating proteomic response to plasma as a distinct component versus low-titer O whole blood (LTOWB), which contains plasma.

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.

Laboratory and clinical haemostatic aberrations in primary dermatologic disease: A review.

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms.Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states.

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.

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.

Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action.

Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate. The standard practice after making the diagnosis includes aggressive resuscitation, anticoagulation, followed by revascularization and resection of necrotic bowel. The role of empiric antibiotics in the management of AMI is not well defined in the literature.