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Journal of Clinical Laboratory Analysis May 2021Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant... (Review)
Review
Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant platelets. Aggregating platelets consist of activated integrin αIIbβ3 and stretch out pseudopods to further attract platelets to the site of injury by connecting with fibrinogen. They mainly gather in the core of the thrombus and perform a secretory function, such as releasing adenosine diphosphate (ADP). Procoagulant platelets promote the formation of thrombin and fibrin by interacting with coagulation factors and can thus be considered as the connector between primary and secondary hemostasis. In addition to their functions in blood coagulation, procoagulant platelets play a proinflammatory role by releasing platelet microparticles and inorganic polyphosphate. Considering these important functions of procoagulant platelets, this subpopulation warrants detailed study to analyze their potential in preventing human diseases. This review summarizes the generation and important characteristics of procoagulant platelets, as well as their potential for preventing the adverse effects associated with current antiplatelet therapies.
Topics: Apoptosis; Biomarkers; Blood Coagulation; Blood Platelets; Humans; Necrosis
PubMed: 33709517
DOI: 10.1002/jcla.23750 -
Anesthesiology Mar 1977Basic knowledge regarding platelet physiology has been reviewed and related to clinical situations where platelet function is critically important. Platelet function...
Basic knowledge regarding platelet physiology has been reviewed and related to clinical situations where platelet function is critically important. Platelet function tests such as aggregation and survival studies, which are research tools now, may soon be available to aid in the diagnosis and management of clinical bleeding problems. A growing understanding of drug-platelet interactions is allowing manipulation of platelets and the clotting system to improve the proganoses for patients who have thromboembolic diseases. Advances in platelet storage and transfusion techniques can save patients who previously might have bled to death. Proper application of the new developments in cardiopulmonary bypass and hemodilution, with attention to platelet and coagulation factor preservation, will contribute to securing hemostasis and conserving blood products.
Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Blood Preservation; Blood Transfusion; Extracorporeal Circulation; Humans; Platelet Adhesiveness; Templates, Genetic; Tourniquets
PubMed: 842874
DOI: 10.1097/00000542-197703000-00008 -
International Journal of Molecular... Aug 2019Platelets are megakaryocyte-derived fragments lacking nuclei and prepped to maintain primary hemostasis by initiating blood clots on injured vascular endothelia.... (Review)
Review
Platelets are megakaryocyte-derived fragments lacking nuclei and prepped to maintain primary hemostasis by initiating blood clots on injured vascular endothelia. Pathologically, platelets undergo the same physiological processes of activation, secretion, and aggregation yet with such pronouncedness that they orchestrate and make headway the progression of atherothrombotic diseases not only through clot formation but also via forcing a pro-inflammatory state. Indeed, nuclear factor-κB (NF-κB) is largely implicated in atherosclerosis and its pathological complication in atherothrombotic diseases due to its transcriptional role in maintaining pro-survival and pro-inflammatory states in vascular and blood cells. On the other hand, we know little on the functions of platelet NF-κB, which seems to function in other non-genomic ways to modulate atherothrombosis. Therein, this review will resemble a rich portfolio for NF-κB in platelets, specifically showing its implications at the levels of platelet survival and function. We will also share the knowledge thus far on the effects of active ingredients on NF-κB in general, as an extrapolative method to highlight the potential therapeutic targeting of NF-κB in coronary diseases. Finally, we will unzip a new horizon on a possible extra-platelet role of platelet NF-κB, which will better expand our knowledge on the etiology and pathophysiology of atherothrombosis.
Topics: Animals; Anti-Inflammatory Agents; Blood Platelets; Humans; NF-kappa B; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 31461836
DOI: 10.3390/ijms20174185 -
British Journal of Haematology Nov 2015Platelet refractoriness can represent a significant clinical problem that complicates the provision of platelet transfusions, is associated with adverse clinical... (Review)
Review
Platelet refractoriness can represent a significant clinical problem that complicates the provision of platelet transfusions, is associated with adverse clinical outcomes and increases health care costs. Although it is most frequently due to non-immune platelet consumption, immunological factors are also often involved. Human leucocyte antigen (HLA) alloimmunization is the most important immune cause. Despite the fact that systematic reviews of the clinical studies evaluating different techniques for selecting HLA compatible platelets have not been powered to demonstrate improved clinical outcomes, platelet refractoriness is currently managed by the provision of HLA-matched or cross matched platelets. This review will address a practical approach to the diagnosis and management of platelet refractoriness while highlighting on-going dilemmas and knowledge gaps.
Topics: Blood Platelets; HLA Antigens; Histocompatibility Testing; Humans; Platelet Transfusion
PubMed: 26194869
DOI: 10.1111/bjh.13597 -
Thrombosis Research Apr 2014While the role of platelets in hemostasis is well characterized from a biological perspective, the biophysical interactions between platelets and their mechanical... (Review)
Review
While the role of platelets in hemostasis is well characterized from a biological perspective, the biophysical interactions between platelets and their mechanical microenvironment are relatively unstudied. The field of cellular mechanics has developed a number of approaches to study the effects of extracellular matrix (ECM)-derived mechanical forces on various cells, and has elucidated that integrin-cytoskeleton-mediated force transduction governs many cellular processes. As platelets adhere and spread via molecular machinery that is similar to that which enables other cells to mechanosense and mechanotransduce forces from their biophysical microenvironment, platelets too are likely governed by the same overarching mechanisms. Indeed, recent platelet mechanobiology studies have revealed that key aspects of platelet physiology and activation are regulated by the mechanical and spatial properties of the ECM microenvironment. At the same time, there are also key differences that make platelets unique in the world of cells-- their size, origin as megakaryocyte fragments, and unique αIIbβ3 integrin-- render their mechanosensing activities particularly interesting. The structurally "simple," anucleate nature of platelets coupled with their high actin concentration (20% of total protein) and integrin density [1] seem to make them ideal for mechanical force generation and transmission. Further studies will enhance our understanding of the role of platelet mechanobiology in hemostasis and thrombosis, potentially leading to new categories of diagnostics that investigate the mechanical properties of clots to determine bleeding risk, as well as therapies that target the mechanotransduction signaling pathway to alter the stability of clots.
Topics: Biophysical Phenomena; Blood Platelets; Hemostasis; Humans; Mechanotransduction, Cellular; Microscopy, Atomic Force
PubMed: 24440140
DOI: 10.1016/j.thromres.2013.12.037 -
The Biochemical Journal Mar 2015Rho GTPases are critical for platelet function. Although the roles of RhoA, Rac and Cdc42 are characterized, platelets express other Rho GTPases, whose activities are... (Review)
Review
Rho GTPases are critical for platelet function. Although the roles of RhoA, Rac and Cdc42 are characterized, platelets express other Rho GTPases, whose activities are less well understood. This review summarizes our understanding of the roles of platelet Rho GTPases and focuses particularly on the functions of Rif and RhoG. In human platelets, Rif interacts with cytoskeleton regulators including formins mDia1 and mDia3, whereas RhoG binds SNARE-complex proteins and cytoskeletal regulators ELMO and DOCK1. Knockout mouse studies suggest that Rif plays no critical functions in platelets, likely due to functional overlap with other Rho GTPases. In contrast, RhoG is essential for normal granule secretion downstream of the collagen receptor GPVI. The central defect in RhoG-/- platelets is reduced dense granule secretion, which impedes integrin activation and aggregation and limits platelet recruitment to growing thrombi under shear, translating into reduced thrombus formation in vivo. Potential avenues for future work on Rho GTPases in platelets are also highlighted, including identification of the key regulator for platelet filopodia formation and investigation of the role of the many Rho GTPase regulators in platelet function in both health and disease.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Signal Transduction; rho GTP-Binding Proteins
PubMed: 25748676
DOI: 10.1042/BJ20141404 -
Journal of Thrombosis and Haemostasis :... Jul 2009Heterodimeric receptors of the beta1 and beta3 integrin families mediate platelet adhesion and aggregation in hemostasis and thrombosis. In resting platelets, integrins... (Review)
Review
Heterodimeric receptors of the beta1 and beta3 integrin families mediate platelet adhesion and aggregation in hemostasis and thrombosis. In resting platelets, integrins are expressed in a low-affinity state but they shift to a high-affinity state and efficiently bind their ligands in response to cellular activation. This review summarizes recent advances in understanding the functional regulation and (patho-) physiological significance of individual platelet integrins with a special focus on studies in genetically modified mice. It is now recognized that beta1 and beta3 integrins have partially redundant roles in the adhesion process and that their activation is regulated by similar mechanisms, involving Ca2+-dependent and -independent signaling events and essential functions of talin-1 and kindlin-3 in the terminal activation step.
Topics: Blood Platelets; Humans; Integrins; Platelet Activation; Platelet Membrane Glycoproteins
PubMed: 19630801
DOI: 10.1111/j.1538-7836.2009.03370.x -
Physiology (Bethesda, Md.) May 2018Blood platelets are involved in a wide range of physiological responses and pathological processes. Recent studies have considerably advanced our understanding of the... (Review)
Review
Blood platelets are involved in a wide range of physiological responses and pathological processes. Recent studies have considerably advanced our understanding of the mechanisms of platelet production and clearance, revealing new connections between the birth and death of these tiny, abundant cells. Key insights have also been gained into how physiological challenges such as inflammation, infection, and chemotherapy can affect megakaryocytes, the cells that produce platelets.
Topics: Animals; Blood Platelets; Humans; Infections; Inflammation; Megakaryocytes
PubMed: 29638183
DOI: 10.1152/physiol.00005.2018 -
Cell Adhesion & Migration Sep 2016The primary physiological function of blood platelets is to seal vascular lesions after injury and form hemostatic thrombi in order to prevent blood loss. This task... (Review)
Review
The primary physiological function of blood platelets is to seal vascular lesions after injury and form hemostatic thrombi in order to prevent blood loss. This task relies on the formation of strong cellular-extracellular matrix interactions in the subendothelial lesions. The cytoskeleton of a platelet is key to all of its functions: its ability to spread, adhere and contract. Despite the medical significance of platelets, there is still no high-resolution structural information of their cytoskeleton. Here, we discuss and present 3-dimensional (3D) structural analysis of intact platelets by using cryo-electron tomography (cryo-ET) and atomic force microscopy (AFM). Cryo-ET provides in situ structural analysis and AFM gives stiffness maps of the platelets. In the future, combining high-resolution structural and mechanical techniques will bring new understanding of how structural changes modulate platelet stiffness during activation and adhesion.
Topics: Animals; Biomechanical Phenomena; Blood Platelets; Humans; Integrins; Models, Biological; Tomography
PubMed: 27104281
DOI: 10.1080/19336918.2016.1173803 -
Current Opinion in Hematology Sep 2014Several decades of work by many investigators have elucidated the major signaling pathways responsible for platelet activation. Still to be fully understood is how these... (Review)
Review
PURPOSE OF REVIEW
Several decades of work by many investigators have elucidated the major signaling pathways responsible for platelet activation. Still to be fully understood is how these pathways are integrated into a single network and how changing conditions within a growing thrombus affect that network. In this review we will consider some of the recent studies that address these issues and describe a model that provides insights into platelet activation as it occurs in vivo.
RECENT FINDINGS
Genetic and pharmacologic studies performed in vivo have demonstrated that platelet activation during hemostasis and thrombosis is heterogeneous. Those studies indicate that distinct platelet activation pathways are not merely redundant, but are coordinated in time and space to achieve an optimal response. This coordination is achieved at least in part by the evolving distribution of platelet agonists and changes in solute transport within a hemostatic plug.
SUMMARY
Studies examining the coordination of platelet signaling in time and space continue to increase our understanding of hemostasis and thrombosis. In addition to helping to decipher platelet biology, the results have implications for the understanding of new and existing antiplatelet agents and their potential risks.
Topics: Animals; Blood Platelets; Cell Shape; Humans; Platelet Activation; Signal Transduction; Vascular System Injuries
PubMed: 25023471
DOI: 10.1097/MOH.0000000000000070