Photothrombolytics: A light-driven technology for the targeted lysis of thrombi.

Occlusive blood clots remain a significant global health challenge and result in emergencies that are main causes of death and disability worldwide. Thrombolytic agents (including tissue plasminogen activator, tPA) are the only pharmacological means to dissolve blood clots. However, these drugs have modest efficacy and severe safety concerns persist.

Attenuation of Atherosclerosis with PAR4 Deficiency: Differential Platelet Outcomes in apoE vs. Ldlr Mice.

Objective: Cardiovascular disease (CVD) is a significant burden globally and, despite current therapeutics, remains the leading cause of death. Platelet inhibitors are of interest in CVD treatment to reduce thrombus formation post-plaque rupture as well their contribution to inflammation throughout the progression of atherosclerosis. Protease activated receptor 4 (PAR4) is a receptor highly expressed by platelets, strongly activated by thrombin, and plays a vital role in platelet activation and aggregation.

Plasma H3Cit-DNA Discriminates Between Cancer and Inflammation in a Cohort of Patients with Unspecific Cancer Symptoms.

Cancer detection is challenging, especially in patients with unspecific cancer symptoms. Biomarkers could identify patients at high risk of cancer. Prior studies indicate that neutrophil extracellular traps (NETs) are associated with cancer, but also with autoimmune and infectious diseases.

Comparison of assays measuring extracellular vesicle tissue factor in plasma samples: communication from the ISTH SSC Subcommittee on Vascular Biology.

Background: Scientific and clinical interest in extracellular vesicles (EVs) is growing. EVs that expose tissue factor (TF) bind factor VII/VIIa and can trigger coagulation. Highly procoagulant TF-exposing EVs are detectable in the circulation in various diseases, such as sepsis, COVID-19, or cancer.

Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target.

A common feature in patients with abdominal aortic aneurysms (AAAs) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA-associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation affects the pathogenesis of AAA.

4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mouse hemostasis model.

Interplay between platelets, coagulation factors, endothelial cells (ECs), and fibrinolytic factors is necessary for effective hemostatic plug formation. This study describes a 4-dimensional (4D) imaging platform to visualize and quantify hemostatic plug components in mice with high spatiotemporal resolution. Fibrin accumulation after laser-induced vascular injury was observed at the platelet plug-EC interface, controlled by the antagonistic balance between fibrin generation and breakdown.

Cancer patients and ischemic stroke.

Patients with cancer have an increased risk of ischemic stroke compared to the general population. Additionally, these patients have a worse prognosis compared to stroke patients without cancer. Activation of coagulation appears to play a key role in the pathophysiology of ischemic stroke in patients with cancer.

Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood.

Plasma kallikrein (PKa) is an important activator of factor XII (FXII) of the contact pathway of coagulation. Several studies have shown that PKa also possesses procoagulant activity independent of FXII, likely through its ability to directly activate FIX. We evaluated the procoagulant activity of PKa using a mouse whole blood (WB) thrombin-generation (TG) assay.

Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

Background: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.

Objectives: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients.

Mucin 1 and venous thrombosis in tumor-bearing mice and patients with cancer.

Introduction: Mucins released from epithelial tumors have been proposed to play a role in cancer-associated thrombosis. Mucin1 (MUC1) is a transmembrane mucin that is overexpressed in a variety of human malignancies, including breast and pancreatic cancer. We analyzed the association of MUC1 and venous thrombosis in a mouse tumor model and in patients with cancer.

Evaluation of the ability of commercial enzyme-linked immunosorbent assays to measure mouse tissue factor.

Background: Tissue factor (TF) is the primary cellular initiator of the blood coagulation cascade. Increased levels of TF expression on circulating monocytes or on extracellular vesicles (EVs) are associated with thrombosis in a variety of diseases, including sepsis and COVID-19.

Objectives: Here, we aimed to evaluate the ability of 4 commercial TF enzyme-linked immunosorbent assays (ELISAs) to measure mouse TF in cells and plasma.

Tissue Factor and COVID-19 Associated Thrombosis.

Microbial infections activate the innate and adaptive immune systems. Pathogen-associated molecular patterns produced by microbes, such as double-stranded RNA, are detected by PRRs (pattern-recognition receptors), such as toll-like receptor 3, and this leads to the expression of interferons and cytokines..

Extracellular Vesicle Tissue Factor Activity Assay.

Tissue factor (TF) is a transmembrane receptor for factor (F) VII and FVIIa. The TF/FVIIa complex initiates the coagulation cascade by activating both FIX and FX. TF is released from cells into the circulation in the form of extracellular vesicles (EVs).

Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

Background: Coagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.

Objectives: To evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer.

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancer-associated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available enzyme-linked immunosorbant assay in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE.

Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice.

The relationship between von Willebrand factor (VWF) and inflammation has attracted considerable attention in recent years. VWF, which is stored in the Weibel-Palade bodies (WPBs) of endothelial cells (ECs), is released from WPBs in response to inflammatory stimuli and is thought to contribute to inflammation by promoting leukocyte extravasation. In this study, lung injury model mice were produced by intratracheal injection with lipopolysaccharides.