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Platelets Feb 2022Dengue virus (DENV) infection is responsible for the development of dengue illness, which can be either asymptomatic, present mild manifestations or evolve to severe... (Review)
Review
Dengue virus (DENV) infection is responsible for the development of dengue illness, which can be either asymptomatic, present mild manifestations or evolve to severe dengue. Thrombocytopenia is an important characteristic during DENV infection, being observed both in mild and severe dengue, although the lowest platelet counts are encountered during severe cases. This review gathers information regarding several mechanisms that have been related to alterations in platelet number and function, leading to thrombocytopenia but also platelet-mediated immune and inflammatory response. On this regard, we highlight that the decrease in platelet counts may be due to bone marrow suppression or consumption of platelets at the periphery. We discuss the infection of hematopoietic progenitors and stromal cells as mechanisms involved in bone marrow suppression. Concerning peripheral consumption of platelets, we addressed the direct infection of platelets by DENV, adhesion of platelets to leukocytes and vascular endothelium and platelet clearance mediated by anti-platelet antibodies. We also focused on platelet involvement on the dengue immunity and pathogenesis through translation and secretion of viral and host factors and through platelet-leukocyte aggregates formation. Hence, the present review highlights important findings related to platelet activation and thrombocytopenia during dengue infection, and also exhibits different mechanisms associated with decreased platelet counts.:Schematic mechanistic representation of platelet-mediated immune responses and thrombocytopenia during dengue infection. (A) DENV-infected platelets secrete cytokines and chemokines and also adhere to activated vascular endothelium. Platelets aggregate with leukocytes, inducing the secretion of NETs and inflammatory mediators by neutrophils and monocytes, respectively. (B) DENV directly infects stromal cells and hematopoietic precursors, including megakaryocytes, which compromises megakaryopoiesis. Both central and peripheric mechanisms contribute to DENV-associated thrombocytopenia.
Topics: Blood Platelets; Dengue; Dengue Virus; Female; Humans; Male; Platelet Count; Thrombocytopenia
PubMed: 34027810
DOI: 10.1080/09537104.2021.1921722 -
Platelets 2019Inherited or acquired disorders of platelet production and function can result in thrombocytopenia and bleeding. Mouse models have proven useful for investigating the...
Inherited or acquired disorders of platelet production and function can result in thrombocytopenia and bleeding. Mouse models have proven useful for investigating the mechanisms that underlie these defects in humans. Precise methods for blood withdrawal, platelet isolation and measurement of platelet parameters are key for the generation of reproducible and conclusive data. Here, we provide three different protocols for mouse platelet isolation to encourage research knowledge transfer between experienced laboratories, while at the same time enabling less experienced researchers to implement a protocol that best suits their local expertise and equipment. We also address the issue that reported mouse platelet count and size vary considerably in the literature by investigating different factors that influence these important platelet parameters, namely: 1) genetic background and gender, 2) choice of analysis method (hematological analyzer or flow cytometry), 3) dilution of the blood sample and 4) choice of anticoagulant. The herein presented results and considerations may serve as a practical guide for both experienced and new researchers in the platelet field.
Topics: Animals; Blood Platelets; Hematology; Male; Mice; Platelet Count
PubMed: 30346859
DOI: 10.1080/09537104.2018.1528345 -
Current Opinion in Hematology Nov 2021This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet... (Review)
Review
PURPOSE OF THE REVIEW
This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet removal with platelet production in the bone marrow in health and disease.
RECENT FINDINGS
This review is focused on the role of carbohydrates, specifically sialic acid moieties, as a central mediator of platelet clearance. We discuss recently identified novel mechanisms of carbohydrate-mediated platelet removal and carbohydrate-binding receptors that mediate platelet removal.
SUMMARY
The platelet production rate by megakaryocytes and removal kinetics controls the circulating platelet count. Alterations in either process can lead to thrombocytopenia (low platelet count) or thrombocytosis (high platelet count) are associated with the risk of bleeding or overt thrombus formation and serious complications. Thus, regulation of a steady-state platelet count is vital in preventing adverse events. There are few mechanisms delineated that shed light on carbohydrates' role in the complex and massive platelet removal process. This review focuses on carbohydrate-related mechanisms that contribute to the control of platelet numbers.
Topics: Blood Platelets; Humans; Megakaryocytes; Platelet Count; Polysaccharides; Thrombopoiesis
PubMed: 34605444
DOI: 10.1097/MOH.0000000000000682 -
Anaesthesiology Intensive Therapy 2015Heparin-induced thrombocytopenia (HIT) is a clinical immune-mediated syndrome; symptoms of HIT result from the development of arterial and venous thrombosis and are... (Review)
Review
Heparin-induced thrombocytopenia (HIT) is a clinical immune-mediated syndrome; symptoms of HIT result from the development of arterial and venous thrombosis and are correlated with the severity of the thrombocytopenia. In all patients receiving heparin preparations in intensive care units, platelet counts should be monitored every 2-3 days throughout therapy, particularly during days 4-14 when HIT is most likely to develop. The major screening tests should always involve a clinical assessment of HIT probability (4Ts or HEP scoring systems) and enzymatic immunoassays (IgG antibodies) for patients with a moderate to high risk of HIT. The full possibilities of such advanced diagnostic procedures are limited in Poland because functional tests are still not widely available. If the diagnosis is questionable, all heparin preparations should be withdrawn and an alternative method of anticoagulation instituted until HIT has been conclusively excluded. The use of new-generation anticoagulants (direct thrombin or Xa factor inhibitors) is currently considered the treatment of choice. Old-generation anticoagulants should not be administered (vitamin K antagonists) as they can aggravate thrombosis. If administered, their action should be reversed by vitamin K once HIT is confirmed. Antithrombotic therapy with "new" anticoagulants should be carried out at least until platelet counts return to the baseline values; the recommended duration of therapy is 4 weeks in patients with isolated thrombocytopenia or 4 months in those with thrombotic complications. Vitamin K antagonists should not be applied until the normal platelet count is restored (usually > 150 G L⁻¹). When the therapy with vitamin K antagonists is reintroduced, "old" antagonists should be administered simultaneously with a "new" anticoagulant for at least 5 days due to an initial decrease in protein C concentration concentration, provided that the therapeutic value of INR is maintained (> 2) for at least 2 days.
Topics: Animals; Anticoagulants; Drug Monitoring; Heparin; Humans; Platelet Count; Poland; Severity of Illness Index; Thrombocytopenia
PubMed: 25751293
DOI: 10.5603/AIT.2015.0006 -
Platelets Mar 2018The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical... (Review)
Review
The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet's role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies-ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)-employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.
Topics: Blood Platelets; Female; Humans; Male; Mean Platelet Volume; Platelet Count
PubMed: 28649937
DOI: 10.1080/09537104.2017.1317732 -
American Journal of Obstetrics &... Jul 2023Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a systematic review and meta-analysis to evaluate the association in pooled samples and in detail.
DATA SOURCES
A systematic literature search was performed using Medline, Embase, ScienceDirect, Web of Science, Cochrane Library, NICHD-DASH, LILACS, and Scopus from inception to April 22, 2022.
STUDY ELIGIBILITY CRITERIA
Observational studies comparing platelet count between women with preeclampsia and normotensive pregnant women were included.
METHODS
The mean differences with 95% confidence interval in platelet count were calculated. Heterogeneity was assessed using I statistics. Sensitivity and subgroup analyses were conducted. Statistical analysis was performed using RevMan 5.3 and ProMeta 3 software.
RESULTS
A total of 56 studies comprising 4892 preeclamptic and 9947 normotensive pregnant women were included. Meta-analysis showed that platelet count was significantly lower in women with preeclampsia than in normotensive controls (overall: mean difference, -32.83; 95% confidence interval, -40.13 to -25.52; P<.00001; I=92%; mild preeclampsia: mean difference, -18.65; 95% confidence interval, -27.17 to -10.14; P<.00001; I=84%; severe preeclampsia: mean difference, -42.61; 95% confidence interval, -57.53 to -27.68; P<.00001; I=94%). Significantly lower platelet count was also observed in the second trimester (mean difference, -28.84; 95% confidence interval, -44.59 to -13.08; P=.0003; I=93%), third trimester (mean difference, -40.67; 95% confidence interval, -52.14 to -29.20; P<.00001; I=92%), and before the diagnosis of preeclampsia (mean difference, -18.81; 95% confidence interval, -29.98 to -7.64; P=.009; I=87%), but not in the first trimester (mean difference, -15.14; 95% confidence interval, -37.71 to 7.43; P=.19; I=71%). Overall, the pooled sensitivity and specificity of platelet count were 0.71 and 0.77, respectively. The area under the curve was 0.80.
CONCLUSION
This meta-analysis confirmed that platelet count was significantly lower in preeclamptic women, irrespective of severity and presence or absence of associated complications, even before the onset of preeclampsia and in the second trimester of pregnancy. Our findings suggest that platelet count may be a potential marker to identify and predict preeclampsia.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Platelet Count; Blood Pressure; Pregnancy Trimester, First; Pregnancy Trimester, Third
PubMed: 37098392
DOI: 10.1016/j.ajogmf.2023.100979 -
Thrombosis Research Dec 2016
Topics: Cardiovascular Diseases; Humans; Neoplasms; Platelet Count; Risk Factors
PubMed: 27837908
DOI: 10.1016/j.thromres.2016.11.001 -
Journal of the American Society of... Feb 2024
Topics: Humans; Platelet Count; Blood Platelets; Case-Control Studies; Renal Insufficiency, Chronic
PubMed: 38300717
DOI: 10.1681/ASN.0000000000000268 -
Seminars in Thrombosis and Hemostasis Apr 2020Extracorporeal membrane oxygenation (ECMO) is a form of life support used to treat neonates, children, and adults with cardiorespiratory failure refractory to... (Review)
Review
Extracorporeal membrane oxygenation (ECMO) is a form of life support used to treat neonates, children, and adults with cardiorespiratory failure refractory to conventional therapy. This therapy requires the use of anticoagulation to prevent clotting in the extracorporeal circuit, but anticoagulation also increases the risk of bleeding on ECMO. Both bleeding and thrombosis remain significant complications on ECMO and balancing these risks is challenging. Acquired platelet dysfunction is common during ECMO and quantitative and qualitative platelet dysfunction contributes to bleeding risk. Optimal platelet count, function, and transfusion thresholds are not well established during pediatric ECMO. In this review, we provide an overview of hemostatic alterations during ECMO, changes in platelet count and function, platelet monitoring techniques, bleeding risk, and future needs to best optimize patient management and care.
Topics: Blood Coagulation; Extracorporeal Membrane Oxygenation; Humans; Platelet Count
PubMed: 32232826
DOI: 10.1055/s-0040-1708542 -
Platelets Dec 2023Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters...
Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 10 /mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 10 /mL, < .0001, moderate (intubation, no ECMO): 208.0 ∙ 10 /mL, < .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 10 /mL, < .0001, 12.2%, = .0003).
Topics: Humans; COVID-19; Blood Platelets; Thrombocytopenia; Platelet Count; Blood Coagulation
PubMed: 36883692
DOI: 10.1080/09537104.2023.2184183