8^th Global Cardiologists and Echocardiography Annual Meeting

Biography

Biography: Mohammed Saied Mohammed Bakeer

Abstract

The initial “waterfall” or “cascade” model for coagulation was proposed in 1964 by MacFarlane, Davie and Ratnoff. Obscure in this model, is the role of the contact (intrinsic) pathway. As the known stimulus for it has been largely non physiological, such as glass and kaolin. Also people with deficiency of factor XII show no significant bleeding tendencies. While the connection between coagulation, inflammation and thrombosis is well known observation, however its exact mechanism was not clear. In recent years there has been a growing body of literature supporting the role of negatively charged,poly anionic linear polymers such as polyphosphate (poly-P) and extracellular nucleic acids (RNA and DNA) in thrombosis and inflammation. Poly-P is a highly anionic, linear polymer of orthophosphate, which is stored as metachromatic granules in many cells. The recent discovery that the dense granules of the platelets are actually a storage of (Poly- P), and the observation that (Poly- P) can strongly stimulate contact pathway has opened a way for a new understanding of coagulation system. Activation of the contact system by long-chain (poly-p) can also be strongly pro-inflammatory, in a manner dependent on factor XII activation and release of bradykinin from high molecular weight kininogen. It was also noted that platelet (poly-p) causes an approximately 3000-fold increase in the rate of back-activation of factor XI by thrombin, enhances the rate of factor V activation to Va by factor XIa. While (poly-p) is released mainly from platelets, extracellular DNA and RNA are released mainly from neutrophils; neutrophil extracellular traps (NETs).Both (poly-p) and (NETs) almost have the same function. Targeting (poly-P) for therapeutic benefit: Genetically knocking down (poly-P) levels in platelets in mice protects against experimentally induced thrombosis. The approach of targeting (poly-P) is either by enzymatic degradation or by neutralizing it by poly cationic inhibitors, the latter approach is proved to be more clinically applicable. Poly cationic inhibitors, such as spermin and many others have been proved to be highly effective antithrombotic agents in mouse model of arterial thrombosis, with much lower bleeding risk compared to heparin. Not only being a potentially attractive as antithrombotic agents, but this approach might also prove to be useful as a way of cutting the link between thrombosis and inflammation. Conclusions. Poly-P and other anionic polymers such as extracellular nucleic acids make up one of newest classes of molecules that function at the nexus of coagulation, inflammation and innate immunity. Our understanding to its physiological role in hemostasis will open the door to the possibility of novel, potentially safer antithrombotic agents.