Thrombin platelet aggregation

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. 

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

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). 

Inhibits platelet aggregation by increasing levels of cAMP Binds protein C, which is then cleaved by thrombin to yield activated protein C this in combination with protein S degrades factors Va and Villa, limiting their actions Activates plasminogen to plas-min, which digests fibrin the action of t-PA is opposed by plasminogen activator inhibitor- (PAI-1)... 

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. 

SNAC is the most potent inhibitor of collagen-induced platelet aggregation in vitro compared to other S-nitrosothiols (SNAP, GSNO, CysNO and HomocysNo). Although it increased cGMP-levels in platelets [47], SNAC only partially inhibited thrombin-induced P-selectin expression on a platelet surface [79]. 

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]. 

B-NOD is a new NO donor compound. It has a chemical NO-releasing group similar to that of NTG, however, it releases NO in vitro and in vivo. After administration of B-NOD in vivo its activity persists for more than 7 h. In vitro, the release of NO from B-NOD was augmented by the presence ofliving cells (blood platelets). B-NOD increased cGMP levels and prevented thrombin-induced platelet aggregation in vitro in the same manner as SNP. In vivo, administration of B-NOD in rabbits did not cause a fall in blood pressure or an increase in heart rate [97]. 

As a typical example of a 6-heteroarylsubstituted dihydropyridazinone exhibiting antithrombotic activity motapizone, NAT 05-239 (63) (CAS 90697-57-7) may serve [96], Compound CCI 17810 (64) (CAS 76283-03-9) bearing a substituted phenyl moiety at C-6 of the pyridazine system has been shown to inhibit potently in vitro human platelet aggregation (induced by collagen, ADP, thrombin or arachidonic acid) with EC50 values in the range of 0.5-10/rg/ml [245], ... 

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. 

Both cyclo(Gly-Tyr) and cyclo(Gly-Phe)significantly inhibited ADP- and thrombin-induced aggregation of isolated platelets. Both DKPs displayed efficacy as antibacterial agents against several bacterial cultures... 

Mechanism of action - Argatroban is a synthetic, direct thrombin inhibitor that reversibly binds to the thrombin active site. It inhibits thrombin-catalyzed or induced reactions, including fibrin formation activation of coagulation factors V, VIII, and XIII protein C and platelet aggregation. 

Platelets aggregation stimulation. Fruit juice, administered intravenously by infusion to dogs at a dose of 5 mL/min, was active. Total infusion was 300 mL h Oil, administered orally to six New Zealand white rabbits fed a commercial diet supplemented with 60 g/kg of coconut oil low in all PUFA for 60 days, produced a platelets aggregation induced by both thrombin and collagen significantly lower with either fish or linseed oil (n-3 PUFA), than with corn oil (n-6 PUFA) or the low PUFA coconut oil . 

Mechanism of Action An antithrombin that inhibits factor Xa and thrombin in the presence of low-molecular-weight heparin. Only slightly influences platelet aggregation, PT, and aPTT. Therapeutic Effect Produces anticoagulation. 

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