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Blood Transfusion = Trasfusione Del... Jul 2019Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while... (Review)
Review
Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while the remaining one-third are used therapeutically to manage active bleeding. These two indications, prophylactic and therapeutic, serve two very distinct purposes and therefore will have two different functional requirements. In addition, disease aetiology in a given patient may require platelets with different functional characteristics. These characteristics can be derived from the various manufacturing methods used in platelet product production, including collection methods, processing methods, and storage options. The iterative combinations of manufacturing methods can result in a number of unique platelet products with different efficacy and safety profiles, which could potentially be used to benefit patient populations by meeting diverse clinical needs. In particular, cold storage of platelet products causes many biochemical and functional changes, of which the most notable characterised to date include increased haemostatic activity and altered expression of molecules inherent to platelet:leucocyte interactions. The in vivo consequences, both short- and long-term, of these molecular and cellular cold-storage-induced changes have yet to be clearly defined. Elucidation of these mechanisms would potentially reveal unique biologies that could be harnessed to provide more targeted therapies. To this end, in this new era of personalised medicine, perhaps there is an opportunity to provide individual patients with platelet products that are tailored to their clinical condition and the specific indication for transfusion.
Topics: Animals; Blood Platelets; Blood Preservation; Cell Communication; Cold Temperature; Endothelial Cells; Hemostasis; Humans; Leukocytes; Platelet Transfusion; Precision Medicine
PubMed: 31385802
DOI: 10.2450/2019.0095-19 -
Platelets Dec 2024Platelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at... (Review)
Review
Platelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at vascular stenosis and near device surfaces. Platelet slip extends the observed biological "slip-bonds" to the boundary of functional gliding without contact. As a result, there is diminished engagement of the coagulation cascade by platelets at these surfaces. Comprehending platelet slip would more precisely direct antithrombotic regimens for different shear environments, including for percutaneous coronary intervention (PCI). In this brief report we promote translation of the proof-of-concept for platelet slip into improved antithrombotic regimens by: (1) reviewing new supporting basic biological science and clinical research for platelet slip; (2) hypothesizing the principal variables that affect platelet slip; (3) applying the consequent construct model in support of-and in some cases to challenge-relevant contemporary guidelines and their foundations (including for urgent, higher-risk PCI); and (4) suggesting future research pathways (both basic and clinical). Should future research demonstrate, explain and control platelet slip, then a paradigm shift for choosing and recommending antithrombotic regimens based on predicted shear rate should follow. Improved clinical outcomes with decreased complications accompanying this paradigm shift for higher-risk PCI would also result in substantive cost savings.
Topics: Humans; Blood Platelets; Fibrinolytic Agents
PubMed: 38773939
DOI: 10.1080/09537104.2024.2353582 -
British Journal of Haematology Apr 2014
Topics: Blood Platelets; Humans; Megakaryocytes; Thrombopoiesis
PubMed: 24690043
DOI: 10.1111/bjh.12799 -
International Journal of Molecular... Jan 2023Platelets play a major role in the processes of primary hemostasis and pathological inflammation-induced thrombosis. In the mid-2000s, several studies expanded the role... (Review)
Review
Platelets play a major role in the processes of primary hemostasis and pathological inflammation-induced thrombosis. In the mid-2000s, several studies expanded the role of these particular cells, placing them in the "immune continuum" and thus changing the understanding of their function in both innate and adaptive immune responses. Among the many receptors they express on their surface, platelets express Toll-Like Receptors (TLRs), key receptors in the inflammatory cell-cell reaction and in the interaction between innate and adaptive immunity. In response to an infectious stimulus, platelets will become differentially activated. Platelet activation is variable depending on whether platelets are activated by a hemostatic or pathogen stimulus. This review highlights the role that platelets play in platelet modulation count and adaptative immune response during viral infection.
Topics: Humans; Blood Platelets; Platelet Activation; Inflammation; Immune System; Virus Diseases; Immunity, Innate
PubMed: 36768333
DOI: 10.3390/ijms24032009 -
Blood May 2010Platelets are classified as terminally differentiated cells that are incapable of cellular division. However, we observe that anucleate human platelets, either...
Platelets are classified as terminally differentiated cells that are incapable of cellular division. However, we observe that anucleate human platelets, either maintained in suspension culture or captured in microdrops, give rise to new cell bodies packed with respiring mitochondria and alpha-granules. Platelet progeny formation also occurs in whole blood cultures. Newly formed platelets are structurally indistinguishable from normal platelets, are able to adhere and spread on extracellular matrix, and display normal signal-dependent expression of surface P-selectin and annexin V. Platelet progeny formation is accompanied by increases in biomass, cellular protein levels, and protein synthesis in expanding populations. Platelet numbers also increase during ex vivo storage. These observations indicate that platelets have a previously unrecognized capacity for producing functional progeny, which involves a form of cell division that does not require a nucleus. Because this new function of platelets occurs outside of the bone marrow milieu, it raises the possibility that thrombopoiesis continues in the bloodstream.
Topics: Annexin A5; Biomarkers; Blood Platelets; Cell Proliferation; Electrophoresis, Gel, Two-Dimensional; Humans; P-Selectin; Platelet Aggregation; Platelet Count; Thrombopoiesis
PubMed: 20086251
DOI: 10.1182/blood-2009-08-239558 -
PloS One 2014Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease,...
Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs) and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.
Topics: Apoptosis; Blood Platelets; Dose-Response Relationship, Drug; Humans; Ibuprofen; Oxidative Stress; Platelet Aggregation; Reactive Oxygen Species
PubMed: 25238069
DOI: 10.1371/journal.pone.0107182 -
British Journal of Pharmacology Dec 2004During haematogenous metastasis, cancer cells migrate to the vasculature and interact with platelets resulting in tumour cell-induced platelet aggregation (TCIPA). We... (Review)
Review
During haematogenous metastasis, cancer cells migrate to the vasculature and interact with platelets resulting in tumour cell-induced platelet aggregation (TCIPA). We review: 1. The biological and clinical significance of TCIPA; 2. Molecular mechanisms involved in platelet aggregation by cancer cells; 3. Strategies for pharmacological regulation of these interactions. We conclude that pharmacological regulation of platelet-cancer cell interactions may reduce the impact of TCIPA on cancer biology.
Topics: Animals; Antineoplastic Agents; Blood Platelets; Humans; Neoplasms; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 15492016
DOI: 10.1038/sj.bjp.0706013 -
The Journal of Clinical Investigation Dec 2005Platelets represent an important linkage between inflammation, thrombosis, and atherogenesis. Inflammation is characterized by interactions among platelets, leukocytes,... (Review)
Review
Platelets represent an important linkage between inflammation, thrombosis, and atherogenesis. Inflammation is characterized by interactions among platelets, leukocytes, and ECs. These interactions trigger autocrine and paracrine activation processes that lead to leukocyte recruitment into the vascular wall. Platelet-induced chronic inflammatory processes at the vascular wall result in development of atherosclerotic lesions and atherothrombosis. This Review highlights the molecular machinery and inflammatory pathways used by platelets to initiate and accelerate atherothrombosis.
Topics: Animals; Arteriosclerosis; Atherosclerosis; Blood Platelets; Cell Adhesion; Disease Models, Animal; Hemostasis; Humans; Inflammation; Models, Biological; Monocytes; Platelet Adhesiveness; Selectins; Thrombosis
PubMed: 16322783
DOI: 10.1172/JCI27196 -
Cancer Metastasis Reviews Jun 2017Platelets are equipped with RNA processing machineries, such as pre-mRNA splicing, pre-miRNA processing, and mRNA translation. Since platelets are devoid of a nucleus,... (Review)
Review
Platelets are equipped with RNA processing machineries, such as pre-mRNA splicing, pre-miRNA processing, and mRNA translation. Since platelets are devoid of a nucleus, most RNA transcripts in platelets are derived from megakaryocytes during thrombocytogenesis. However, platelets can also ingest RNA molecules during circulation and/or interaction with other cell types. Since platelets were first described by Bizzozero in 1881, their well-established role in hemostasis and thrombosis has been intensively studied. However, in the past decades, the list of biological processes in which platelets play an important role keeps expanding. In this review, we discuss how platelet RNA biomarker signatures can be altered in the presence of cancer.
Topics: Animals; Blood Platelets; Humans; Neoplasms; RNA, Neoplasm
PubMed: 28681241
DOI: 10.1007/s10555-017-9674-0 -
Blood Aug 2012Platelet (PLT) production represents the final stage of megakaryocyte (MK) development. During differentiation, bone marrow MKs extend and release long, branched proPLTs... (Review)
Review
Platelet (PLT) production represents the final stage of megakaryocyte (MK) development. During differentiation, bone marrow MKs extend and release long, branched proPLTs into sinusoidal blood vessels, which undergo repeated abscissions to yield circulating PLTs. Circular-prePLTs are dynamic intermediate structures in this sequence that have the capacity to reversibly convert into barbell-proPLTs and may be related to "young PLTs" and "large PLTs" of both inherited and acquired macrothrombocytopenias. Conversion is regulated by the diameter and thickness of the peripheral microtubule coil, and PLTs are capable of enlarging in culture to generate barbell-proPLTs that divide to yield 2 smaller PLT products. Because PLT number and size are inversely proportional, this raises the question: do macrothrombocytopenias represent a failure in the intermediate stages of PLT production? This review aims to bring together and contextualize our current understanding of terminal PLT production against the backdrop of human macrothrombocytopenias to establish how "large PLTs" observed in both conditions are similar, how they are different, and what they can teach us about PLT formation. A better understanding of the cytoskeletal mechanisms that regulate PLT formation and determine PLT size offers the promise of improved therapies for clinical disorders of PLT production and an important source of PLTs for infusion.
Topics: Animals; Blood Platelets; Cell Size; Cytoskeleton; Gene Expression Regulation; Humans; Thrombocytopenia; Thrombopoiesis
PubMed: 22665937
DOI: 10.1182/blood-2012-04-408724