Role of platelet activation and fibrin formation in thrombogenesis

Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor

The platelet ATP and ADP receptors.

peer reviewedThis review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination

ATP Augments von Willebrand Factor-dependent Shear-induced Platelet Aggregation through Ca2+-Calmodulin and Myosin Light Chain Kinase Activation

peer reviewedShear stress triggers von Willebrand factor (VWF) binding to platelet glycoprotein Ibalpha and subsequent integrin alpha(IIb)beta(3)-dependent platelet aggregation. Concomitantly, nucleotides are released from plateletdense granules, and ADP is known to contribute to shear-induced platelet aggregation (SIPA). This study shows that ATP also contributes to SIPA. The ATP-gated P2X(1) ion channel induces MLC-mediated cytoskeletal rearrangements that increases platelet degranulation during VWF-triggered platelet activation

Estimating the Cost-Effectiveness of Quality-Improving Interventions in Oral Anticoagulation Management within General Practice

AbstractObjectivesA clinical trial, “Belgian Improvement Study on Oral Anticoagulation Therapy (BISOAT),” significantly improved the quality after implementing four different quality-improving interventions in four randomly divided groups of general practitioners (GPs). The quality-improving interventions consisted of multifaceted education with or without feedback reports on their performance, international normalized ratio (INR) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy. The quality improvement in INR control versus baseline was similar in the four groups. The aim of the current study was to calculate the cost-effectiveness and influencing factors of the four quality-improving interventions compared with usual care.MethodsActivity-based costing techniques with questionnaires were used to determine the global costs per patient per month in the different intervention groups. Effectiveness data were obtained from the BISOAT study. Cost-effectiveness was expressed as cost per additional day within a 0.5 range from INR target.ResultsThe one-time cost of multifaceted education was €49,997 for the whole study. Monthly continuous costs per intervention ranged between €37 and €54 per patient. Using the CoaguChek in combination with the multifaceted education was associated with net savings and quality improvement, hence dominated usual care. Sensitivity analyses showed improved cost-effectiveness with extended duration and with increased program size.ConclusionImplementation of the combination multifaceted education with the use of the CoaguChek is a cost-effective new organizational model of oral anticoagulation management in general practice

Does the P(2X1del) variant lacking 17 amino acids in its extracellular domain represent a relevant functional ion channel in platelets?

In this letter, we questionned the existence of a ADP responsive P2X1 protein variant in platelets

The P2Y1 receptor antagonist adenosine-2',5'-diphosphate non-selectively antagonizes the platelet P2X1 ion channel.

This letter indicates a lack of specificity of a platelet P2Y1 receptor antagonist