Platelets thrombin and

IpJH, FusterV Israel D, Badimon L, BadimonJ, ChesebroJH. The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty, J Am Coll Cardiol 1991 17(6 suppl B) 77B-88B,... 

Phospholipase C (both p and y) catalyzes the hydrolysis of Phosphatidyl inositol bisphosphate (PIPj) leading to the generation of diacylglycerol (DAG) and inositol trisphosphate (IP,). In platelets, thrombin and thromboxane-A, (TxA,) stimulate PLC-p. PLC-P has three isotypes. It is known that PLC-pi and PLC-P3 are activated by G-protein... 

Fibrin sealant, thrombin and collagen, fibrin sealant plus collagen, and platelet gels... 

The formation of a platelet aggregate requires the recruitment of additional platelets from the blood stream to the injured vessel wall. This process is executed through a variety of diffusible mediators which act through G-protein-coupled receptors. The main mediators involved in this process are adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin (factor Ila). These mediators of the second phase of platelet activation are formed in different ways. While ADP is secreted from platelets by exocytosis, the release of TXA2 follows its new formation in activated platelets. Thrombin can be formed on the surface of activated platelets (see Fig. 2). 

Thrombin and other agents cause platelet aggregation, which involves a variety of biochemical and morphologic events. Stimulation of phosphofipase C and the polyphosphoinositide pathway is a key event in platelet activation, but other processes are also involved. 

Fibrinolytic agents have prothrombotic properties as well. The plasmin generated by thrombolysis leads to the production of thrombin, which is a potent platelet activator and converts fibrinogen to fibrin. Indeed, studies have shown early reocclusion in as many as 17% of the patients treated with lAT and 34% of the patients treated with IV rt-PA. Therefore, a strong rationale exists for the adjuvant use of antithrombotic agents. 

Yamazaki H, Yamaguchi T, Yamaguchi A, et al. 1992. Effect of halocarbons and styrene on thrombin and calcium ionosphere induced activation of rabbit platelets. Chemosphere 25 665-673. 

Heparin-induced thrombocytopenia A clinical syndrome of IgG antibody production against the heparin-platelet factor 4 complex occurring in approximately 1% to 5% of patients exposed to either heparin or low-molecular-weight heparin. Heparin-induced thrombocytopenia results in excess production of thrombin, platelet aggregation, and thrombocytopenia (due to platelet clumping), often leading to venous and arterial thrombosis, amputation of extremities, and death. 

Fig. 2. Generation of tenase and prothrombin complexes. PPL represents the anionic phospholipid surface provided by the platelets (platelet phospholipid). Cleavage of prothrombin by the prothrombinase complex results in the formation of thrombin and the release of a small fragment called prothrombin fragment 1.2 (PFI.2).

GEA-3175 is more stable than GEA-3162 in vitro but still retains its biological activity [95]. The release of NO and NO2 by GEA 3175 was increased 140-fold in the presence of human plasma, as analyzed by ozone chemiluminescence [94]. GEA 3175 inhibited agonist-induced platelet aggregation and induced a more than 4-fold increase in platelet cGMP without affecting cAMP levels [94]. Thrombin-stimulated rises in the cytosolic free Ca2+ concentration and secretion were dose-dependently inhibited by GEA 3175. GEA 3175 showed a reduced capacity to inhibit platelet aggregation of uremic platelets compared to controls [96]. 

The plasma proteinase, thrombin, a procoagulant enzyme with effects on platelets, endothelial cells and smooth muscle, has been shown to stimulate bone-marrow-derived murine mast cells to release histamine and jS-hexos-aminidase [135]. This secretory response is rapid, reaching a maximum in 1-2 min, and dose-dependent, beginning at about 0.1 U of thrombin and plateauing at 0.5 U thrombin. 

Many studies have shown that ginseng has a protective effect on the development of atherosclerosis that may lead to myocardial infarction and other cardiovascular diseases. The preventive effects on cardiovascular diseases of ginseng include its potential antihypertensive and antiatherosclerotic effects. Ginsenosides are likely to be responsible for some of these effects as they have been shown to have inhibitory effects on platelet aggregation and to suppress thrombin formation as well as an effect on blood vessel contraction. 

Another method for reducing osmolality of the injection was achieved by the synthesis of mono-carboxylic dimers, leading to the development of ioxaglic acid (600 mOsm kg at 320 mgl mL ). Because of specific properties on platelet functions and thrombin generation, this agent is widely used for interventional procedures [3]. 

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