Platelets and galectins

A major function of platelets is keeping the vascular system intact. Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug. Activation of platelets is therefore crucial for normal hemostasis; however, uncontrolled platelet activation may also lead to the formation of occlusive thrombi that can cause ischemic events. Although they are essential for proper hemostasis, platelet function extends to physiologic processes such as tissue repair, wound remodeling and antimicrobial host defense, or pathologic conditions such as thrombosis, atherosclerosis, chronic inflammatory diseases and cancer. Platelets can be activated by soluble molecules including thrombin, thromboxane A2 (TXA2), adenosine diphosphate (ADP), serotonin or by adhesive extracellular matrix (ECM) proteins such as von Willebrand factor (vWF) and collagen. Here we describe recent advances in the activation of platelets by non-canonical platelet agonists such as galectins. By acting either in soluble or immobilized form, these glycan-binding proteins trigger all platelet activation responses through modulation of discrete signaling pathways. We also offer new hypotheses and some speculations about the role of platelet-galectin interactions not only in hemostasis and thrombosis but also in inflammation and related diseases such as atherosclerosis and cancer.Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Microfluidic flow chambers using reconstituted blood to model hemostasis and platelet transfusion in vitro

Blood platelets prepared for transfusion gradually lose hemostatic function during storage. Platelet function can be investigated using a variety of (indirect) in vitro experiments, but none of these is as comprehensive as microfluidic flow chambers. In this protocol, the reconstitution of thrombocytopenic fresh blood with stored blood bank platelets is used to simulate platelet transfusion. Next, the reconstituted sample is perfused in microfluidic flow chambers which mimic hemostasis on exposed subendothelial matrix proteins. Effects of blood donation, transport, component separation, storage and pathogen inactivation can be measured in paired experimental designs. This allows reliable comparison of the impact every manipulation in blood component preparation has on hemostasis. Our results demonstrate the impact of temperature cycling, shear rates, platelet concentration and storage duration on platelet function. In conclusion, this protocol analyzes the function of blood bank platelets and this ultimately aids in optimization of the processing chain including phlebotomy, transport, component preparation, storage and transfusion

An in vitro study of the adhesion of blood platelets onto vascular catheters. Part I

The adhesion of human blood platelets onto vascular catheters was studied using a specially designed perfusion chamber. Polyurethane catheters were exposed to citrated human blood for different periods (up to 20 min) and at different wall shear rates (190, 260, 330 sec-1). The rate of platelet adhesion was determined using 111In-labeled platelets, while the morphology of adhering platelets was investigated using scanning electron microscopy. A linear increase in platelet adhesion was found within the first 10 min of perfusion, after which a plateau value was reached. The number of adhering platelets did not vary significantly with the shear rates applied, which may indicate that within the range of shear rates studied, the adhesion of platelets onto the catheter surface is mainly determined by the rate of the reaction between the platelets and the material surface. Catheters coated with a conjugate of heparin and albumin showed a four- to five-fold reduction in platelet adhesion as compared to uncoated catheters. This reduction in platelet adhesion was not only due to the presence of albumin moieties at the surface but also to the presence of heparin residues in the adsorbed albumin-heparin conjugate

Of pools, oceans, and the Dead Sea.

In a comprehensive study in this issue of Blood, Carden and colleagues describe the importance of the tonicity of IV fluids used in the treatment of patients with sickle cell disease (SCD) during vaso-occlusive crises (VOCs). Hypertonic fluids decreased sickle red blood cell (sRBC) deformability, increased occlusion, and increased sRBC adhesion in microfluidic human microvasculature models. Hypotonic fluids decreased sRBC adhesion but prolonged sRBC transit time. Fluids with intermediate tonicities resulted in optimal changes that reduced the risk of vaso-occlusion. © 2017 by The American Society of Hematology

Thrombozytenhemmung und -aktivierung: Mechanismen und klinische Implikationen

Zusammenfassung : Die Empfindlichkeit der Aktivierung von Thrombozyten ist Teil des delikaten Gleichgewichts, welches Hämostase von Thrombose unterscheidet. Unter physiologischen Bedingungen wird es durch die Hemmung der Thrombozytenaktivität und Entfernung von Agonisten erhalten. Unter pathologischen prothrombotischen Bedingungen versucht der Mediziner, das Gleichgewicht mit Hilfe von Arzneimitteln wiederherzustellen. Die Resultate dieser Behandlungen verbessern sich stetig, aber dennoch sind ein besseres Verständnis der Mechanismen und die Suche nach alternativen Inhibitoren nach wie vor wichti

The subendothelial circulatory system in the splenic trabecular vein and the intrasplenic cell recurrence.

In the spleen of patient exposed to atomic bomb as well as in the infective spleen and leukemic spleen sometimes characteristic endothelium of the trabecular vein can be observed and this canalicula in the trabecular vein communicates with reticulum tissue of the pulp. In the subendothelial circulatory canalicula of the splenic trabecular vein there can be observed emigrating picture of various leucocytes of the vein passing this subendothelium (chemotaxisis) and these cells emigrate and accumulate outside the splenic trabecula (intrasplenic cell recurrence). Arterial blood circulates in these subendothelial canaliculae and these canaliculae are not lymph canaliculae as demonstrated by JAGER and ROSSLE. Many leucocytes flow back into the pulp outside the trabecula through this circulatory system. Also in the peritrabecular pulp a new formation of collagen fibers and a considerable number of plasma cells can be observed in various infective spleens, and splenic trabecular area is the regenerating center and reactive center in the spleen, just as lymph follicle in the spleen.</p

Deposition of endothelial fibronectin on polymeric surfaces

Cellular fibronectin is deposited on tissue culture polystyrene during the adhesion and spreading of cultured human endothelial cells (HEC). Following the seeding of HEC upon this polymer, larger amounts of fibronectin are deposited as both cell density and incubation time increase. Our results indicate that the ability to deposit cellular fibronectin onto a polymeric surface is a condition for the spreading and proliferation of HEC

Von Willebrand Disease

Von Willebrand Disease (VWD) is a blood clotting disorder characterized by low levels of the Von Willebrand Factor (VWF) in the blood. VWF is functions to bind platelets and promote clotting of the blood when vascular injury occurs. Therefore, VWD leads to decreased or impaired clotting. There are three main types and four subtypes of VWD (type 1, 2A, 2B, 2N, 2M, and 3). Each type of VWD increases in severity. VWD is diagnosed preliminarily through a personal and family history and physical examination. Upon indications toward the possibility of a bleeding disorder, an initial hemostasis evaluation is performed followed by an initial VWD assay. The most common treatment for VWD is the use of desmopressin to promote VWF secretion into the bloodstream. New research addresses VWF- related proteins such as SNAP23 and ADAMTS-13 as well as organ transplantation and their respective effects on VWD