-
Transfusion Medicine Reviews Apr 1997
Review
Topics: Blood Group Incompatibility; Blood Platelets; Blood Preservation; Blood Specimen Collection; Humans; Platelet Activation; Platelet Aggregation; Platelet Transfusion
PubMed: 9140172
DOI: 10.1053/tm.1997.0110130 -
Transfusion and Apheresis Science :... Feb 2001The relationship between the platelet storage lesion (PSL) and programmed cell death (apoptosis) is poorly understood. Nevertheless, there is some experimental evidence... (Review)
Review
The relationship between the platelet storage lesion (PSL) and programmed cell death (apoptosis) is poorly understood. Nevertheless, there is some experimental evidence that platelets contain most of the components of the apoptosis machinery and both the apoptotic process and the PSL lead to platelet activation and microvesiculation with expression of phosphatidyl serine (PS) on the outer layer of cell membrane, a hallmark of all nucleated cells. The PS exposure is believed to contribute to the development of inflammatory or immunomodulation process, to the regulation of haemostatic balance and the ultimate clearance of dead or fragmented cells from the circulation. While there is no doubt that apoptosis, as a form of genetically encoded programmed cell death in nucleated cells, is triggered by several signalling stimuli at the nuclear level, there is some doubt as to whether platelets, as enucleated cells have retained the memory of the "parental" megakaryocytes for apoptosis or whether platelet mitochondrial DNA has a major role in both the apoptotic process and the PSL. The storage lesion occurs during processing and storage subsequent to mechanical trauma, hypoxic conditions or exposure to cold. In this brief report some observational evidence is provided in support of the notion that the PSL and apoptosis may be related to each other, despite the fact that, in contrast to the 'parental' megakarocyte, the platelets appear to survive upon stimulation with a high concentration of protein kinase inhibitors such as staurosporine (STS), in the presence of cycloheximide (CHX) which inhibit protein synthesis. This is a model which is often used to regulate the level of survival signals. The possible relevance of platelet microvesiculation to transfusion practice is briefly discussed.
Topics: Apoptosis; Blood Platelets; Blood Preservation; Humans; Leukocytes; Mitochondria
PubMed: 11515605
DOI: 10.1016/s0955-3886(00)00134-x -
Trends in Pharmacological Sciences Feb 1993Platelets have the capacity to generate oxygen-derived free radicals and are often present at inflammatory foci with other free-radical-generating cells such as white... (Review)
Review
Platelets have the capacity to generate oxygen-derived free radicals and are often present at inflammatory foci with other free-radical-generating cells such as white blood cells. Free radicals can modify platelet adhesion and aggregation directly or through effects on the vascular endothelium, which generates prostacyclin and nitric oxide. To defend against the overproduction of free radicals the body manufactures endogenous scavengers, which can be of enzymic or non-enzymic origin. Daniela Salvemini and Regina Botting describe how free-radical scavengers may be used therapeutically to regulate the platelet reactivity involved in many pathological phenomena.
Topics: Animals; Blood Platelets; Free Radical Scavengers; Free Radicals; Humans
PubMed: 8480372
DOI: 10.1016/0165-6147(93)90028-i -
Transfusion Medicine Reviews Jan 2003Platelets are activated by a number of stimuli resulting in the expression and/or activation of surface receptors, secretion of vasoactive substances, adhesion,... (Review)
Review
Platelets are activated by a number of stimuli resulting in the expression and/or activation of surface receptors, secretion of vasoactive substances, adhesion, aggregation, and finally thrombus formation. These events are propagated by a process known as transmembrane signaling, which relays the activating signal from the platelet membrane (eg, von Willebrand Factor binding to glycoprotein Ib) to the inside of the platelet which then serves to activate the platelet via a cascade of biochemical interactions. Inhibition of these transmembrane signaling molecules with a variety of available inhibitors or antagonists can in many cases prevent the platelet from becoming activated. An awareness of the mechanisms involved in platelet transmembrane signaling and the recent availability of new reagents to inhibit signaling may provide us with additional means to prevent platelet activation and perhaps even ameliorate the platelet storage lesion. This review will provide an introduction to the field of platelet transmembrane signaling and give an overview of some of the platelet signaling mechanisms that are relevant to transfusion medicine.
Topics: Blood Platelets; Humans; Platelet Activation; Platelet Transfusion; Proteins; Signal Transduction
PubMed: 12522771
DOI: 10.1053/tmrv.2003.50002 -
The New England Journal of Medicine Jun 1969
Review
Topics: Adenosine Triphosphate; Animals; Blood Platelets; Blood Proteins; Blood Transfusion; Glycolysis; Hemostasis; Humans; Lipid Metabolism; Megakaryocytes; Microscopy, Electron; Serotonin; Thrombocytopenia; Thrombosis
PubMed: 4890562
DOI: 10.1056/NEJM196906122802405 -
British Journal of Clinical Pharmacology Aug 1990
Review
Topics: Blood Platelets; Fibrinolytic Agents; Humans; Platelet Function Tests
PubMed: 2206781
DOI: 10.1111/j.1365-2125.1990.tb03762.x -
Platelets Jun 2018The open canalicular system (OCS) is an internal membrane structure found in platelets. First identified 50 years ago, the OCS comprises a tunneling network of... (Review)
Review
The open canalicular system (OCS) is an internal membrane structure found in platelets. First identified 50 years ago, the OCS comprises a tunneling network of surface-connected channels that appear to play an important role in platelet function. Yet, our understanding of how the OCS forms, how it functions, and what might regulate its structure and behavior remains fairly rudimentary. Structural abnormalities of the OCS are observed in some human platelet disorders. Yet, because platelets from these patients display multiple defects, the specific contribution of any OCS dysregulation to the impaired platelet function is unclear. However, recent studies have begun to shed light on mechanisms that regulate the OCS structure and to understand what influence the OCS has on overall platelet function. Advances in cellular imaging techniques have allowed whole-cell visualization of the OCS, providing the opportunity for a more detailed structural examination. Furthermore, recent work indicates that the modulation of the OCS structure may be sufficient to impact in vivo platelet function, opening up the intriguing possibility of manipulating the OCS structure as an anti-thrombotic approach. On the 50 anniversary of its discovery, we review here what is known about OCS structure and function, and outline some of the key microscopy tools for studying this intriguing internal membrane system.
Topics: Blood Platelets; Humans; Microscopy, Electron; Platelet Activation; Platelet Function Tests; Thrombosis
PubMed: 29442528
DOI: 10.1080/09537104.2018.1431388 -
Blood Coagulation & Fibrinolysis : An... Apr 1991The recipients of multiple platelet transfusions frequently develop alloantibodies directed against the human leucocyte antigens (HLA) present on both leucocytes and... (Review)
Review
The recipients of multiple platelet transfusions frequently develop alloantibodies directed against the human leucocyte antigens (HLA) present on both leucocytes and platelets. Such alloimmunization (AI) may result in refractoriness to further platelet transfusions. Contaminating leucocytes bearing Class II HLA and present in platelet concentrates (PC) are responsible for the formation of HLA antibodies and their removal by filtration reduces the rate of recipient AI. Ultraviolet irradiation (UVR) of PC at an appropriate dose inactivates the contaminating mononuclear leucocytes so that responses in vitro to mitogens and alloantigens are abrogated. It seems likely that UV-irradiation of donor dendritic cells (DC) is important in preventing in vitro responses to alloantigens and in vivo allosensitization. At the same time, satisfactory platelet function and structure is retained when measured by in vitro tests. In vivo assessments of platelet recovery and survival in healthy subjects and the ability to correct the bleeding time in thrombocytopenic patients are comparable to non-irradiated PC. Prospective studies are now in progress to determine if UVR will reduce recipient AI to HLA in multiply-transfused patients with leukaemia and lymphoma.
Topics: Antigens, Surface; Blood Platelets; Blood Transfusion; Humans; Immunization; Isoantigens; Platelet Transfusion; Ultraviolet Rays
PubMed: 1893070
DOI: 10.1097/00001721-199104000-00025 -
Methods in Molecular Biology (Clifton,... 2017Analysis of platelet function is widely used for diagnostic work-up in patients with increased bleeding tendency. During the last decades, platelet function testing has...
Analysis of platelet function is widely used for diagnostic work-up in patients with increased bleeding tendency. During the last decades, platelet function testing has also been introduced for evaluation of antiplatelet therapy, but this is still recommended for research purposes only. Platelet function can also be assessed for hyper-aggregability, but this is less often evaluated. Light transmission aggregometry (LTA) was introduced in the early 1960s and has since been considered the gold standard. This optical detection system is based on changes in turbidity measured as a change in light transmission, which is proportional to the extent of platelet aggregation induced by addition of an agonist. LTA is a flexible method, as different agonists can be used in varying concentrations, but performance of the test requires large blood volumes and experienced laboratory technicians as well as specialized personal to interpret results. In the present chapter, a protocol for LTA is described including all steps from pre-analytical preparation to interpretation of results.
Topics: Blood Platelets; Humans; Light; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests
PubMed: 28804839
DOI: 10.1007/978-1-4939-7196-1_25 -
Thrombosis and Haemostasis Feb 2023The mechanisms underlying platelet granule release are not fully understood. The actin cytoskeleton serves as the platelet's structural framework that is remodeled...
BACKGROUND AND OBJECTIVE
The mechanisms underlying platelet granule release are not fully understood. The actin cytoskeleton serves as the platelet's structural framework that is remodeled upon platelet activation. Gelsolin is a calcium-dependent protein that severs and caps existing actin filaments although its role in modulating platelet granule exocytosis is unknown.
METHODS
The hemostatic function of wild-type () and gelsolin null ( ) mice was measured ex vivo by rotational thromboelastometry analysis of whole blood. Platelets were purified from and mouse blood and activated with thrombin. Platelet aggregation was assessed by light-transmission aggregometry. Clot retraction was measured to assess outside-in integrin signaling. Adenosine triphosphate (ATP) release and surface P-selectin were measured as markers of dense- and α-granule secretion, respectively.
RESULTS
The kinetics of agonist-induced aggregation, clot retraction, and ATP release were accelerated in platelets relative to . However, levels of surface P-selectin were diminished in platelets. ATP release was also accelerated in platelets pretreated with the actin-depolymerizing drug cytochalasin D, thus mimicking the kinetics observed in platelets. Conversely, ATP release kinetics were normalized in platelets treated with the actin polymerization agonist jasplakinolide. Rab27b and Munc13-4 are vesicle-priming proteins known to promote dense granule secretion. Co-immunoprecipitation indicates that the association between Rab27b and Munc13-4 is enhanced in platelets.
CONCLUSIONS
Gelsolin regulates the kinetics of hemostasis by modulating the platelet's actin cytoskeleton and the protein machinery of dense granule exocytosis.
Topics: Mice; Animals; Gelsolin; Actins; P-Selectin; Actin Cytoskeleton; Blood Platelets; Hemostasis; Platelet Aggregation; Adenosine Triphosphate
PubMed: 36522181
DOI: 10.1055/s-0042-1758800