thromboembolic disease is a common cause of morbidity and mortality. thrombin plays a key role in thrombotic events and thrombin inhibition represents a therapeutic event for thromboembolic events and has been identified as a target of therapy of its pivotal role in coagulation process. anticoagulation is a major intervention for the management of arterial and venous thromboembolic events. dabi...

Thromboembolic disease is a common cause of morbidity and mortality. Thrombin plays a key role in thrombotic events and thrombin inhibition represents a therapeutic event for thromboembolic events and has been identified as a target of therapy of its pivotal role in coagulation process. Anticoagulation is a major intervention for the management of arterial and venous thromboembolic events. Dabi...

The rational design of a novel class trivalent thrombin inhibitors is described through the hybridization natural sulfopeptides produced by blood feeding organisms. hybrid were rapidly assembled using peptide ligation chemistry and shown to exhibit femtomolar inhibition constants against thrombin. A lead inhibitor also showed potent generation platelet aggregation in vitro, as well antithrombot...

Objective: To investigate time to maximal platelet inhibition after an oral loading dose of ASA. The effect ex vivo reversal by desmopressin (DDAVP) was also studied. Methods: Ten healthy volunteers were given a 300 mg ASA-tablet. Blood sampled at 0, 15, 30, 60, 120 and 180 minutes. DDAVP added the samples taken Samples analysed with Multiplate® aggregometer (MEA) using arachidonic acid (AA), c...

Based on the structure of natural product andrographolide, a series novel 12-quinoline substituted derivatives 9 were designed and synthesized. In preliminary biological evaluation, these synthesized compounds showed prominent anti-platelet aggregation activities in response to thrombin adenosine diphosphate (ADP) agonists. Among them, compound 9o (inhibition rate 55.73%, IC50 0.36 µM/L) had hi...

Despite possessing only 32 residues, the tsetse thrombin inhibitor (TTI) is among most potent anticoagulants described, with sub-picomolar inhibitory activity against thrombin. Unexpectedly, TTI isolated from fly 2000-fold more active and 180 Da heavier than synthetic recombinant variants. We predicted presence of a tyrosine O-sulfate post-translational modification TTI, prompting us to investi...

Factor D, when preincubated with platelet suspensions, at concentrations as low as 1.2 micrograms/ml, inhibited thrombin-induced platelet aggregation. No inhibition of collagen or arachidonic acid-induced platelet aggregation was found. Inhibition occurred, but to a lesser extent, when thrombin and factor D were added to platelets at the same time. No inhibition occurred when factor D was added...

Assembly of ternary thrombin-heparin-fibrin complexes, formed when fibrin binds to exosite 1 on thrombin and fibrin-bound heparin binds to exosite 2, produces a 58- and 247-fold reduction in the heparin-catalyzed rate of thrombin inhibition by antithrombin and heparin cofactor II, respectively. The greater reduction for heparin cofactor II reflects its requirement for access to exosite 1 during...

Besides its critical role in hemostasis, the serine protease thrombin also participates in wound healing, inflammation, and atherosclerosis. Thrombin is inhibited by the serpins antithrombin and heparin cofactor II (HCiI) in reactions that are accelerated markedly by specific glycosaminoglycans. Following vascular injury, thrombin must be inhibited at both intravascular and extravascular sites ...