Objective— After activation at the site of vascular injury, platelets differentiate into 2 subpopulations, exhibiting either proaggregatory or procoagulant phenotype. Although the functional role of proaggregatory platelets is well established, the physiological significance of procoagulant platelets, the dynamics of their formation, and spatial distribution in thrombus remain elusive. Approach and Results— Using transmission electron microscopy and fluorescence microscopy of arterial thrombi formed in vivo after ferric chloride–induced injury of carotid artery or mechanical injury of abdominal aorta in mice, we demonstrate that procoagulant platelets are located at the periphery of the formed thrombi. Real-time cell tracking during thrombus formation ex vivo revealed that procoagulant platelets originate from different locations within the thrombus and subsequently translocate towards its periphery. Such redistribution of procoagulant platelets was followed by generation of fibrin at thrombus surface. Using in silico model, we show that the outward translocation of procoagulant platelets can be driven by the contraction of the forming thrombi, which mechanically expels these nonaggregating cells to thrombus periphery. In line with the suggested mechanism, procoagulant platelets failed to translocate and remained inside the thrombi formed ex vivo in blood derived from nonmuscle myosin ( MYH9 )-deficient mice. Ring-like distribution of procoagulant platelets and fibrin around the thrombus observed with blood of humans and wild-type mice was not present in thrombi of MYH9 -knockout mice, confirming a major role of thrombus contraction in this phenomenon. Conclusions— Contraction of arterial thrombus is responsible for the mechanical extrusion of procoagulant platelets to its periphery, leading to heterogeneous structure of thrombus exterior.

Shear rate gradients promote a bi-phasic thrombus formation on weak adhesive proteins, such as fibrinogen in a VWF-dependent manner.

The paper examines the economic linkages between the post-Soviet states from the point of view of the financial and economic crisis of 2008–2009. It aims to find out whether the interdependence between the countries of the former Soviet Union is still large enough that crises in individual countries affect the economic development in the neighboring states, and assesses the impact of the crisis itself on the linkages between the former Soviet republics. The evidence is mixed: while some channels of interdependence deteriorated over the last decade, others became more important, and some were even strengthened by the crisis itself.

Blood flow is a major regulator of hemostasis and arterial thrombosis. The current view is that low and intermediate flows occur in intact healthy vessels, while high shear levels (>2,000 s-1) are reached in stenosed arteries, notably during thrombosis. To date, the shear rates occurring at the edge of a lesion in an otherwise healthy vessel are nevertheless unknown. The aim of this work was to measure the shear rates prevailing in wounds in a context relevant to hemostasis. Three models of vessel puncture and transection were developed and characterized for a study which was implemented in mice and humans. Doppler probe measurements supplemented by a computational model revealed that shear rates at the edge of a wound reached high values, with medians of 22,000 s-1, 25,000 s-1 and 7,000 s-1 after puncture of the murine carotid artery, aorta or saphenous vein, respectively. Similar shear levels were observed after transection of the mouse spermatic artery. These results were confirmed in a human venous puncture model, where shear rates in a catheter implanted in the cubital vein reached 2,000-27,000 s-1. In all models, the high shear conditions were accompanied by elevated levels of elongational flow exceeding 1,000 s-1. In the puncture model, the shear rates decreased steeply with increasing injury size. This phenomenon could be explained by the low hydrodynamic resistance of the injuries as compared to that of the downstream vessel network. These findings show that high shear rates are relevant to hemostasis and not exclusive to arterial thrombosis.

Objective: Integrins are key regulators of various platelet functions. The pathophysiological importance of most platelet integrins has been investigated, with the exception of α5β1, a receptor for fibronectin. The aim of this study was to characterize the role of α5β1 in megakaryopoiesis, platelet function, and to determine its importance in hemostasis and arterial thrombosis. Approach and results: We generated a mouse strain deficient for integrin α5β1 on megakaryocytes and platelets (PF4Cre-α5-/-). PF4Cre-α5-/- mice were viable, fertile and presented no apparent signs of abnormality. Megakaryopoiesis appears unaltered as evidence by a normal megakaryocytes morphology and development, which is in agreement with a normal platelet count. Expression of the main platelet receptors and the response of PF4Cre-α5-/- platelets to a series of agonists were all completely normal. Adhesion and aggregation of PF4Cre-α5-/- platelets under shear flow on fibrinogen, laminin or von Willebrand factor were unimpaired. In contrast, PF4Cre-α5-/- platelets displayed a marked decrease in adhesion, activation and aggregation on fibrillar cellular fibronectin and collagen. PF4Cre-α5-/- mice presented no defect in a tail-bleeding time assay and no increase in inflammatory bleeding in a reverse passive Arthus model and a lipopolysaccharide pulmonary inflammation model. Finally, no defects were observed in three distinct experimental models of arterial thrombosis based on ferric chloride-induced injury of the carotid artery, mechanical injury of the abdominal aorta or laser-induced injury of mesenteric vessels. Conclusion: In summary, this study shows that platelet integrin α5β1 is a key receptor for fibrillar cellular fibronectin but is dispensable in hemostasis and arterial thrombosis.

Platelets are small, nuclear-free cells whose main function is to stop bleeding. In addition to performing a hemostatic function, platelets are also involved in immune and inflammatory processes. Extensive experimental data suggest that platelets support tumor metastasis and their activation plays a critical role in cancer progression. In the circulatory system, platelets protect tumor cells from immune elimination and promote their arrest at the endothelium, supporting the formation of secondary lesions. Due to the significant contribution of platelets to tumor cells survival and propagation, antithrombotic drugs are considered as a novel anti-metastasis approach. In this article, the authors set a goal to summarize and update the currently existing knowledge about the molecular mechanisms and the role of platelets-tumor cells interaction, as well as to discuss the possibility of platelets receptors as anti-metastasis targets.

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On the basis of the existing typologies study classification of retirement and pre-retirementage workers has been conducted according to the signs of possibility to continue their labor activity. Complex information about the age-related changes in the behavior of workers in the process of their labor activity has been obtained. The conclusions are used to determine the of socio-economic management effects with regard to the employment of this category of workers adequate to their state.