Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems.

Background: Human serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo. The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic Maillard reaction that denatures plasma proteins and forms advanced glycation end products (AGEs). HSA-AGE is a prevalent misfolded protein in patients with DM and is associated with factor XII activation and downstream proinflammatory kallikrein-kinin system activity without any associated procoagulant activity of the intrinsic pathway.

Novel interaction of properdin and coagulation factor XI: Crosstalk between complement and coagulation.

Background: Evidence of crosstalk between the complement and coagulation cascades exists, and dysregulation of either pathway can lead to serious thromboinflammatory events. Both the intrinsic pathway of coagulation and the alternative pathway of complement interact with anionic surfaces, such as glycosaminoglycans. Hitherto, there is no evidence for a direct interaction of properdin (factor P [FP]), the only known positive regulator of complement, with coagulation factor XI (FXI) or activated FXI (FXIa).

Drugs in phase I and II clinical development for the prevention of stroke in patients with atrial fibrillation.

Introduction: Atrial fibrillation is the most frequently diagnosed cardiac arrhythmia globally and is associated with ischemic stroke and heart failure. Patients with atrial fibrillation are typically prescribed long-term anticoagulants in the form of either vitamin K antagonists or non-vitamin K antagonist oral anticoagulants; however, both carry a potential risk of adverse bleeding.

Areas Covered: This paper sheds light on emerging anticoagulant agents which target clotting factors XI and XII, or their activated forms - XIa and XIIa, respectively, within the intrinsic coagulation pathway.

Kallikrein directly interacts with and activates Factor IX, resulting in thrombin generation and fibrin formation independent of Factor XI.

Kallikrein (PKa), generated by activation of its precursor prekallikrein (PK), plays a role in the contact activation phase of coagulation and functions in the kallikrein-kinin system to generate bradykinin. The general dogma has been that the contribution of PKa to the coagulation cascade is dependent on its action on FXII. Recently this dogma has been challenged by studies in human plasma showing thrombin generation due to PKa activity on FIX and also by murine studies showing formation of FIXa-antithrombin complexes in FXI deficient mice.

Observations on clot properties in atrial fibrillation: Relation to renal function and choice of anticoagulant.

Introduction: Atrial fibrillation (AF) is associated with increased risk of stroke and thromboembolism. Patients with AF have a higher incidence of renal impairment, which may influence the risks of systemic thromboembolism or bleeding. We determined how different oral anticoagulants affect plasma clot properties and whether progressive renal dysfunction affects plasma clot properties in patients on warfarin.

Evaluation of the Total Thrombus-Formation System (T-TAS): application to human and mouse blood analysis.

The Total Thrombus-formation Analyser System (T-TAS) is a whole blood flow chamber system for the measurement of thrombus formation under variable shear stress conditions. Our current study sought to evaluate the potential utility of the T-TAS for the measurement of thrombus formation within human and mouse whole blood. T-TAS microchips (collagen, PL chip; collagen/tissue thromboplastin, AR chip) were used to analyze platelet (PL) or fibrin-rich thrombus formation, respectively.

The role of activated coagulation factor XII in overall clot stability and fibrinolysis.

Activated coagulation factor XII (α-FXIIa) is able to bind to fibrin(ogen) and increases the density and stiffness of the fibrin clot. Conversely, proteins of the contact system and the fibrinolytic system show a high degree of homology and α-FXIIa can convert plasminogen into plasmin resulting in fibrin degradation. Therefore, we studied the contribution of α-FXIIa to overall clot stability and plasmin driven fibrinolysis in the absence and presence of tissue plasminogen activator (tPA).

Social network methods for endemic foci of syphilis: a pilot project.

Background: Social network methods have improved our understanding of sexually transmitted disease transmission dynamics, and may be of use in routine field operations for partner notification.

Goal: To augment traditional syphilis-control activities with social network methods in an Atlanta area with high syphilis morbidity.

Study Design: Disease investigators conducted interviews, used network diagrams to prioritize their work, and relied on network connections for finding hard-to-reach persons.