Blood coagulation platelet activation, inhibition

Plasma Inhibitors, In Vivo Anticoagulants. Fourteen naturally occurring compounds that normally exert an inhibiting effect on the activity of coagulation, platelet function, and fibrinolytic activity and complement systems have been identified within the circulating blood. 

Protease nexin 2 is identical to the secreted form of the amyloid precursor protein containing the Kunitz-type serine protease inhibitor domain (128,129), Protease nexin 2 circulates in blood stored as a platelet a-granule protein, which is secreted upon platelet activation (127). Protease nexin 2 inhibits trypsin- and chymotrypsin-like serine proteases and is also a potent inhibitor of factor Xla (126,127,128). Its location in platelets and its ability to inhibit factor Xla suggests a role in regulating blood coagulation for protease nexin 2. 

Another site for regulating blood coagulation and subsequent thrombus formation is at the level of the platelets (87). Antiplatelet drugs work by inhibiting platelet activation via a number of different mechanisms (87,88). The major role of antiplatelet drugs is in the prevention of ischemic complications in patients with coronary diseases (89). These drugs also are effective in combination with moderate-intensity anticoagulants for patients with atrial fibrillation. 

Nylander S, Mattsson C. Thrombin-induced platelet activation and its inhibition by anticoagulants with different modes of action. Blood Coagul Fibrinolysis 2003 14 159-167. 

HDL inhibits monocyte chemotaxis, inhibits the adhesion of monocyte and blood cell to vascular endothelium, inhibits endothelial dysfunction and apoptosis, inhibits LDL oxidation, inhibits complement activation, reduces platelet aggregability and coagulation, inhibits platelet activation, and inhibits factor X activation. HDL helps maintain endothelial integrity, facilitate vascular relaxation, stimulates the proliferation of EC and SMC, stimulates the synthesis of prostacyclin and natriuretic peptide C in EC, stimulates protein C and S activation, and may favor fibrinolysis. These functions are exerted by different components of HDL, this complexity emphasizes that changes in HDL functioning rather than plasma HDL-C levels determine the anti-atherogenicity of therapeutic alterations of HDL metabolism (reviewed in refs. 499 and 500). 

Early studies indicate that combined GP Ilb/IIIa inhibition with rt-PA thrombolysis may improve clinical and MRI outcomes after acute ischemic stroke, with an acceptable safety prohle. The dual targeting of platelets and hbrin by combination therapy may provide synergistic benefits, including increased arterial recanalization, reduced microvascular thrombosis, reduced arterial reocclusion, and less rt-PA-mediated blood-brain barrier injury and secondary activation of the coagulation system. 

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