The brilliant green complete single collection 7-8 rar

However, it is also required for haemostatic mechanisms that terminate bleeding. Fibrin constitutes a key component of thrombi. Currently, available anticoagulants such as heparin derivatives, vitamin K antagonists (for example, warfarin) and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation 2. Anticoagulant therapy interferes with the formation of clots within the vasculature and is the mainstay of treatment for the prevention and management of thromboembolic events.

Venous and arterial thromboembolic diseases such as pulmonary embolism, myocardial infarction and stroke are collectively the most common cause of mortality in the developed world 1. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.

In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. PPX and PPX_О”12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. Both PPX and PPX_О”12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation.

Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_О”12) binds to the polymer without degrading it. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Polyphosphate is an inorganic procoagulant polymer.

The brilliant green complete single collection 7-8 rar