Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.

The genomes of positive-sense RNA viruses encode polyproteins that are essential for mediating viral replication. These viral polyproteins must undergo proteolysis (also termed polyprotein processing) to generate functional protein units. This proteolysis can be performed by virally-encoded proteases as well as host cellular proteases, and is generally believed to be a key step in regulating viral replication.

Plasma from patients with pulmonary embolism show aggregates that reduce after anticoagulation.

Background: Microclots, a term also used for amyloid fibrin(ogen) particles and henceforth named aggregates, have recently been reported in the plasma of patients with COVID-19 and long COVID. These aggregates have been implicated in the thrombotic complications of these diseases.

Methods: Plasma samples from 35 patients with acute pulmonary embolism were collected and analysed by laser scanning confocal microscopy and scanning electron microscopy before and after clotting.

Fibrin-glycoprotein VI interaction increases platelet procoagulant activity and impacts clot structure.

Background: The glycoprotein VI (GPVI) signaling pathway was previously reported to direct procoagulant platelet activity through collagen binding. However, the impact of GPVI-fibrin interaction on procoagulant platelet development and how it modulates the clot structure are unknown.

Objectives: To determine the effect of GPVI-fibrin interaction on the platelet phenotype and its impact on the clot structure.

High fibrinogen γ' levels in patient plasma increase clot formation at arterial and venous shear.

Fibrinogen γ' accounts for 3% to 40% of plasma fibrinogen. Earlier studies indicated that fibrinogen γ' forms altered fibrin clots under static conditions, whereas clinically, altered plasma γ' levels are associated with arterial and venous thrombosis. However, the effects of static vs flow conditions on the role of γ' throughout the pathophysiological range is unknown.

The Role of Fibrin(ogen) in Wound Healing and Infection Control.

Fibrinogen, one of the most abundant plasma proteins playing a key role in hemostasis, is an important modulator of wound healing and host defense against microbes. In the current review, we address the role of fibrin(ogen) throughout the process of wound healing and subsequent tissue repair. Initially fibrin(ogen) acts as a provisional matrix supporting incoming leukocytes and acting as reservoir for growth factors.

Thrombus Structural Composition in Cardiovascular Disease.

Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke, or venous thromboembolism. Thrombosis occurs when a thrombus forms inside blood vessels disrupting blood flow. Developments in thrombectomy to remove thrombi from vessels have provided new opportunities to study thrombus composition which may help to understand mechanisms of disease and underpin improvements in treatments.

Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement-mediated intravascular hemolysis and thrombosis. The increased incidence of PNH-driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement-mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients.

Recurrent venous thromboembolism patients form clots with lower elastic modulus than those formed by patients with non-recurrent disease.

Essentials Venous thromboembolism (VTE) recurrence leads to decreased clot elastic modulus in plasma. Recurrent VTE is not linked to changes in clot structure, fiber radius, or factor XIII activity. Other plasma components may play a role in VTE recurrence.

Affimer proteins as a tool to modulate fibrinolysis, stabilize the blood clot, and reduce bleeding complications.

Bleeding complications secondary to surgery, trauma, or coagulation disorders are important causes of morbidity and mortality. Although fibrin sealants are considered to minimize blood loss, this is not widely adopted because of its high cost and/or risk for infection. We present a novel methodology employing nonantibody fibrinogen-binding proteins, termed Affimers, to stabilize fibrin networks with the potential to control excessive bleeding.

Impact of γ'γ' fibrinogen interaction with red blood cells on fibrin clots.

Aim: γ' fibrinogen has been associated with thrombosis. Here the interactions between γ'γ' or γAγA fibrinogen and red blood cells (RBCs), and their role on fibrin clot properties were studied.

Materials & Methods: Atomic Force microscopy (AFM)-based force spectroscopy, rheological, electron and confocal microscopy, and computational approaches were conducted for both fibrinogen variants.

A fibrin biofilm covers blood clots and protects from microbial invasion.

Hemostasis requires conversion of fibrinogen to fibrin fibers that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining clots in human and mouse models.

The RGD sequence on the Aα chain of fibrinogen is essential for binding to its erythrocyte receptor.

Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased by high plasma fibrinogen levels. Here, the effect of different fibrinogen mutations on binding to its human erythrocyte receptor was assessed in order to identify the interaction sites.

Methods: Three fibrinogen variants were tested, specifically mutated in their putative integrin recognition sites on the Aα chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type fibrinogen.

Sensing adhesion forces between erythrocytes and γ' fibrinogen, modulating fibrin clot architecture and function.

Plasma fibrinogen includes an alternatively spliced γ-chain variant (γ'), which mainly exists as a heterodimer (γAγ') and has been associated with thrombosis. We tested γAγ' fibrinogen-red blood cells (RBCs) interaction using atomic force microscopy-based force spectroscopy, magnetic tweezers, fibrin clot permeability, scanning electron microscopy and laser scanning confocal microscopy. Data reveal higher work necessary for RBC-RBC detachment in the presence of γAγ' rather than γAγA fibrinogen.

The prothrombotic state in paroxysmal nocturnal hemoglobinuria: a multifaceted source.

Paroxysmal nocturnal hemoglobinuria is a rare acquired hematologic disorder, the most serious complication of which is thrombosis. The increased incidence of thrombosis in paroxysmal nocturnal hemoglobinuria is still poorly understood, but unlike many other thrombotic disorders, predominantly involves complement-mediated mechanisms. This review article discusses the different factors that contribute to the increased risk of thrombosis in paroxysmal nocturnal hemoglobinuria.

The (Patho)physiology of Fibrinogen γ'.

Fibrinogen γ' is a splice variant of the fibrinogen γ-chain, which leads to a negatively charged extension at the C-terminus of the γ-chain. In fibrinogen, the splice variant appears mainly as a heterodimer with the common γA chain, as γA/γ' fibrinogen. This variant has been shown to modulate thrombin and factor XIII (FXIII) activity, influence clot architecture, and lack a platelet-binding site.

Thrombin and fibrinogen γ' impact clot structure by marked effects on intrafibrillar structure and protofibril packing.

Previous studies have shown effects of thrombin and fibrinogen γ' on clot structure. However, structural information was obtained using electron microscopy, which requires sample dehydration. Our aim was to investigate the role of thrombin and fibrinogen γ' in modulating fibrin structure under fully hydrated conditions.

Common FXIII and fibrinogen polymorphisms in abdominal aortic aneurysms.

Introduction: Abdominal aortic aneurysms (AAA) are characterized by a progressive dilatation of the abdominal aorta, and are associated with a high risk of rupture once the dilatation exceeds 55 mm in diameter. A large proportion of AAA develops an intraluminal thrombus, which contributes to hypoxia, inflammation and tissue degradation. We have previously shown that patients with AAA produce clots with altered structure which is more resistant to fibrinolysis.