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Clinical Chemistry and Laboratory... Aug 2014Abstract Inherited platelet disorders (IPDs) are the general and common denomination of a broad number of different rare and congenital pathologies affecting platelets.... (Review)
Review
Abstract Inherited platelet disorders (IPDs) are the general and common denomination of a broad number of different rare and congenital pathologies affecting platelets. Even if these disorders are characterized by widely heterogeneous clinical presentations, all of them are commonly present as defects in hemostasis. Platelet number and/or function are affected by a wide spectrum of severity. IPDs might be associated with defects in bone marrow megakaryocytopoiesis and, rarely, with somatic defects. Although in the last few years new insights in the genetic bases and pathophysiology of IPDs have greatly improved our knowledge of these disorders, much effort still needs to be made in the field of laboratory diagnosis. This review discusses the laboratory approach for the differential diagnosis of the most common IPDs, suggesting a common multistep flowchart model which starts from the simpler test (platelet count) ending with the more selective and sophisticated analyses.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Laboratories
PubMed: 24698825
DOI: 10.1515/cclm-2014-0131 -
Hepatology Communications Feb 2022Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19)... (Review)
Review
Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19) symptoms caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Additionally, SARS-CoV-2 infection is associated with acute-on-chronic liver failure in patients with cirrhosis and has a notably elevated mortality in patients with alcohol-related liver disease compared to other etiologies. Direct viral infection of the liver with SARS-CoV-2 remains controversial, and alternative pathophysiologic explanations for its hepatic effects are an area of active investigation. In this review, we discuss the effects of SARS-CoV-2 and the inflammatory environment it creates on endothelial cells and platelets more generally and then with a hepatic focus. In doing this, we present vascular inflammation and thrombosis as a potential mechanism of liver injury and liver-related complications in COVID-19.
Topics: Blood Platelet Disorders; COVID-19; Endothelium, Vascular; Humans; Inflammation; Liver Diseases; Thrombosis
PubMed: 34658172
DOI: 10.1002/hep4.1843 -
Platelets Jan 2017
Topics: Blood Platelet Disorders; Blood Platelets; Genomics; Humans; Platelet Count; Platelet Function Tests
PubMed: 28095213
DOI: 10.1080/09537104.2016.1262013 -
Blood Jun 2016Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide... (Review)
Review
Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).(1) The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein-protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management.
Topics: Blood Platelet Disorders; Blood Platelets; DNA; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Molecular Diagnostic Techniques; Rare Diseases; Thrombopoiesis
PubMed: 27095789
DOI: 10.1182/blood-2016-03-378588 -
International Journal of Molecular... Apr 2022Cardiovascular complications remain the leading cause of morbidity and mortality in individuals with diabetes, driven by interlinked metabolic, inflammatory, and... (Review)
Review
Cardiovascular complications remain the leading cause of morbidity and mortality in individuals with diabetes, driven by interlinked metabolic, inflammatory, and thrombotic changes. Hyperglycaemia, insulin resistance/deficiency, dyslipidaemia, and associated oxidative stress have been linked to abnormal platelet function leading to hyperactivity, and thus increasing vascular thrombotic risk. However, emerging evidence suggests platelets also contribute to low-grade inflammation and additionally possess the ability to interact with circulating immune cells, further driving vascular thrombo-inflammatory pathways. This narrative review highlights the role of platelets in inflammatory and immune processes beyond typical thrombotic effects and the impact these mechanisms have on cardiovascular disease in diabetes. We discuss pathways for platelet-induced inflammation and how platelet reprogramming in diabetes contributes to the high cardiovascular risk that characterises this population. Fully understanding the mechanistic pathways for platelet-induced vascular pathology will allow for the development of more effective management strategies that deal with the causes rather than the consequences of platelet function abnormalities in diabetes.
Topics: Blood Platelet Disorders; Blood Platelets; Diabetes Mellitus; Humans; Inflammation; Thrombosis
PubMed: 35563363
DOI: 10.3390/ijms23094973 -
Journal of Thrombosis and Haemostasis :... Jun 2015The gene variants responsible for the primary genotype of many platelet disorders have now been identified. Next-generation sequencing technology (NGST), mainly exome... (Review)
Review
The gene variants responsible for the primary genotype of many platelet disorders have now been identified. Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, CalDAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). Often disorders of platelet function are associated with a modified platelet production with changes in platelet number and size and can accompany malfunction of other organs or tissues. Most families have private mutations, and gene variants may prevent protein synthesis, abrogate function, or result in aberrant activated proteins. Nevertheless, bleeding severity is difficult to predict by genotype alone suggesting other factors. A major new challenge of NGST is to identify these factors and help improve patient care. This review concentrates on recent developments and is illustrated from personal observations.
Topics: Animals; Blood Platelet Disorders; Blood Platelets; DNA Mutational Analysis; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Hemorrhage; Hemostasis; Heredity; High-Throughput Nucleotide Sequencing; Humans; Mutation; Phenotype; Risk Factors; Signal Transduction
PubMed: 26149024
DOI: 10.1111/jth.12898 -
International Journal of Molecular... Sep 2021Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles... (Review)
Review
Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles are tightly regulated by a complex network of signalling pathways. Mass spectrometry-based proteomic techniques are contributing not only to the identification and quantification of new platelet proteins, but also reveal post-translational modifications of these molecules, such as acetylation, glycosylation and phosphorylation. Moreover, target proteomic analysis of platelets can provide molecular biomarkers for genetic aberrations with established or non-established links to platelet dysfunctions. In this report, we review 67 reports regarding platelet proteomic analysis and signalling on a molecular base. Collectively, these provide detailed insight into the: (i) technical developments and limitations of the assessment of platelet (sub)proteomes; (ii) molecular protein changes upon ageing of platelets; (iii) complexity of platelet signalling pathways and functions in response to collagen, rhodocytin, thrombin, thromboxane A and ADP; (iv) proteomic effects of endothelial-derived mediators such as prostacyclin and the anti-platelet drug aspirin; and (v) molecular protein changes in platelets from patients with congenital disorders or cardiovascular disease. However, sample sizes are still low and the roles of differentially expressed proteins are often unknown. Based on the practical and technical possibilities and limitations, we provide a perspective for further improvements of the platelet proteomic field.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Platelet Activation; Protein Processing, Post-Translational; Proteome; Proteomics; Signal Transduction
PubMed: 34576024
DOI: 10.3390/ijms22189860 -
American Journal of Hematology Apr 2017The "platelet function analyzer" (PFA)-100 was first introduced to us in 1995. Since then, the instrument has appeared in over 50 reviews and almost 1000 publications.... (Review)
Review
The "platelet function analyzer" (PFA)-100 was first introduced to us in 1995. Since then, the instrument has appeared in over 50 reviews and almost 1000 publications. Recently, the PFA-100 has been "upgraded" to the PFA-200, which has transformed the user interface and electronic management, but retained the fundamental mechanics, and essentially provides the same results. The PFA-100/200 has conceivable clinical utility to screen for von Willebrand Disease (VWD) and platelet disorders, and in monitoring desmopressin (DDAVP) therapy in both, and possibly anti-platelet therapy. Its great strengths are its usage simplicity and sensitivity to conditions affecting primary hemostasis. However, as a "global" test, its limitation is that closure time (CT) test results are neither predictive of, nor specific for, any individual disorder. However, utilized properly, the PFA-100/200 reflects a valuable addition to hemostasis laboratories involved in identification or therapeutic-monitoring of disorders of primary hemostasis.
Topics: Blood Platelet Disorders; Clinical Laboratory Techniques; Drug Monitoring; Hemostasis; Humans; Platelet Function Tests
PubMed: 27935090
DOI: 10.1002/ajh.24620 -
Journal of Thrombosis and Haemostasis :... Mar 2018Chronic heart failure (HF) is a major emerging healthcare problem, associated with a high morbidity and mortality. Left ventricular assist devices (LVADs) have emerged... (Review)
Review
Chronic heart failure (HF) is a major emerging healthcare problem, associated with a high morbidity and mortality. Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage HF. Despite its great benefit, the use of LVAD is associated with a high risk of complications. Bleeding, pump thrombosis and thromboembolic events are frequently observed complications, with bleeding complications occurring in over a third of the patients. Although the design of the third-generation LVAD has improved greatly, these hemostatic complications still occur. The introduction of an LVAD into the circulatory system results in an altered hematological balance as a consequence of blood-pump interactions, changes in hemodynamics, the rheology, and the concomitant need for anticoagulation while implanted with an LVAD. The majority, if not all, LVAD patients experience a form of platelet dysfunction and impaired von Willebrand factor activity, leading to acquired coagulopathy disorders. Different diagnostic tools and treatment strategies have been reported; however, they require validation in LVAD patients. The present review focuses on acquired coagulopathies, describing the incidence, impact and underlying mechanism of acquired coagulopathy disorders in patients supported by LVADs. In addition, we will discuss diagnostic and management strategies for these acquired coagulopathies.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelet Disorders; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Hemodynamics; Hemostasis; Heparin; Humans; Incidence; Rheology; Risk Factors; Thrombocytopenia; Thromboembolism; Thrombosis; von Willebrand Diseases; von Willebrand Factor
PubMed: 29274191
DOI: 10.1111/jth.13933 -
Critical Reviews in Oncology/hematology Mar 2015Platelets, once considered mediators of hemostasis and thrombosis, are now known to be involved in wound healing, inflammation, cardiovascular diseases, diabetes,... (Review)
Review
Platelets, once considered mediators of hemostasis and thrombosis, are now known to be involved in wound healing, inflammation, cardiovascular diseases, diabetes, arthritis, and cancer. Recent reports attest that platelets possess the cellular machinery to undergo apoptosis and that platelet apoptosis can be triggered by myriad stimuli including chemical and physical agonists, and pathophysiological conditions. Augmented rate of platelet apoptosis leads to thrombocytopenia, bleeding disorders and microparticle generation. Despite knowing the significant role of platelets in health and disease, and that any alterations in platelet functions can wreak havoc to the health, the offshoot reactions of therapeutic drugs on platelets and the far-reaching consequences are often neglected. The present review focuses on the impact of platelet apoptosis and the role of platelet-derived microparticles on different pathophysiological conditions. It also touches upon the effects of biologicals on platelets, and discusses the need to overcome the adverse effects of pro-apoptotic drugs through auxiliary therapy.
Topics: Apoptosis; Blood Platelet Disorders; Blood Platelets; Cell-Derived Microparticles; Humans
PubMed: 25439323
DOI: 10.1016/j.critrevonc.2014.11.002