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Blood Aug 2022Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased...
Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased platelet destruction. In the absence of a diagnostic test, ITP must be differentiated from other thrombocytopenic disorders, including inherited platelet disorders. In addition, a diagnosis of secondary ITP due to a primary immune deficiency with immune dysregulation may not be apparent at diagnosis but can alter management and should be considered in an expanding number of clinical scenarios. The diagnostic evaluation of children with thrombocytopenia will vary based on the clinical history and laboratory features. Access to genotyping has broadened the ability to specify the etiology of thrombocytopenia, whereas increasing access to immunophenotyping, functional immunologic and platelet assays, and biochemical markers has allowed for more in-depth evaluation of patients. With this greater availability of testing, diagnostic algorithms in patients with thrombocytopenia have become complex. In this article, we highlight the diagnostic evaluation of thrombocytopenia in children with a focus on ITP, including consideration of underlying genetic and immune disorders, and use hypothetical patient cases to describe disease manifestations and strategies for treatment of pediatric ITP.
Topics: Biomarkers; Blood Platelets; Child; Humans; Leukopenia; Neuroblastoma; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 34479363
DOI: 10.1182/blood.2020006480 -
Nature Reviews. Cardiology Mar 2021The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in... (Review)
Review
The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.
Topics: Administration, Inhalation; Anticoagulants; Blood Coagulation Disorders; Blood Platelet Disorders; COVID-19; Endothelium, Vascular; Endothelium-Dependent Relaxing Factors; Epoprostenol; Heart Disease Risk Factors; Humans; Iloprost; Inflammation; Nitric Oxide; Platelet Aggregation Inhibitors; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Thrombosis; Thrombotic Microangiopathies; Vascular Diseases; Vasodilator Agents; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 33214651
DOI: 10.1038/s41569-020-00469-1 -
Equine Veterinary Journal Jan 2021Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases... (Review)
Review
Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases and how they are diagnosed. These diseases include haemophilia A, von Willebrand disease, prekallikrein deficiency, Glanzmann's Thrombasthenia and Atypical Equine Thrombasthenia. Exercise-induced pulmonary haemorrhage also has a proposed genetic component. Genetic mutations have been identified for haemophilia A and Glanzmann's Thrombasthenia in the horse. Mutations are known for von Willebrand disease and prekallikrein deficiency in other species. In the absence of genetic tests, bleeding disorders are typically diagnosed by measuring platelet function, von Willebrand factor, and other coagulation protein levels and activities. For autosomal recessive diseases, genetic testing can prevent the breeding of two carriers.
Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Hemorrhage; Hemostasis; Horse Diseases; Horses; Thrombasthenia
PubMed: 32463964
DOI: 10.1111/evj.13290 -
Hamostaseologie Oct 2023
Topics: Humans; COVID-19; Thrombin; Platelet Glycoprotein GPIb-IX Complex; Blood Platelet Disorders
PubMed: 37857294
DOI: 10.1055/s-0043-1776437 -
Journal of Thrombosis and Haemostasis :... Jun 2015We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to... (Review)
Review
We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.
Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Factor V Deficiency; Gene Transfer Techniques; Genetic Predisposition to Disease; Genetic Therapy; Hemophilia A; Humans; Platelet Transfusion; Treatment Outcome; Urokinase-Type Plasminogen Activator
PubMed: 26149015
DOI: 10.1111/jth.12938 -
Ugeskrift For Laeger Oct 2021Inherited platelet disorders (IPD) cover a heterogenous group of disorders with large differences in severity, disease mechanisms and prevalence. Pathogenic variants in... (Review)
Review
Inherited platelet disorders (IPD) cover a heterogenous group of disorders with large differences in severity, disease mechanisms and prevalence. Pathogenic variants in more than 60 different genes, associated with megakaryocyte or platelet number and/or function, are causal of IPD. Due to disease heterogeneity IPDs are often difficult to diagnose, problematic to manage and underestimated. In the past decade, genetic diagnostics using whole-genome sequencing has revolutionised the field by identifying numerous novel genes involved in IPD aetiology as described in this review.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Whole Genome Sequencing
PubMed: 34709163
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Jan 2021Heparin-induced thrombocytopenia is an immune-mediated disorder caused by antibodies that recognize complexes of platelet factor 4 and heparin. Thrombosis is a central... (Review)
Review
Heparin-induced thrombocytopenia is an immune-mediated disorder caused by antibodies that recognize complexes of platelet factor 4 and heparin. Thrombosis is a central and unpredictable feature of this syndrome. Despite optimal management, disease morbidity and mortality from thrombosis remain high. The hypercoagulable state in heparin-induced thrombocytopenia is biologically distinct from other thrombophilic disorders in that clinical complications are directly attributable to circulating ultra-large immune complexes. In some individuals, ultra-large immune complexes elicit unchecked cellular procoagulant responses that culminate in thrombosis. To date, the clinical and biologic risk factors associated with thrombotic risk in heparin-induced thrombocytopenia remain elusive. This review will summarize our current understanding of thrombosis in heparin-induced thrombocytopenia with attention to its clinical features, cellular mechanisms, and its management.
Topics: Animals; Antibodies; Anticoagulants; Antithrombins; Blood Coagulation; Factor Xa Inhibitors; Heparin; Humans; Platelet Factor 4; Risk Factors; Thrombocytopenia; Thrombosis
PubMed: 33267665
DOI: 10.1161/ATVBAHA.120.315445 -
Blood Reviews Jan 2017Recent years have seen increasing recognition of a subgroup of inherited platelet function disorders which are due to defects in transcription factors that are required... (Review)
Review
Recent years have seen increasing recognition of a subgroup of inherited platelet function disorders which are due to defects in transcription factors that are required to regulate megakaryopoiesis and platelet production. Thus, germline mutations in the genes encoding the haematopoietic transcription factors RUNX1, GATA-1, FLI1, GFI1b and ETV6 have been associated with both quantitative and qualitative platelet abnormalities, and variable bleeding symptoms in the affected patients. Some of the transcription factor defects are also associated with an increased predisposition to haematologic malignancies (RUNX1, ETV6), abnormal erythropoiesis (GATA-1, GFI1b, ETV6) and immune dysfunction (FLI1). The persistence of MYH10 expression in platelets is a surrogate marker for FLI1 and RUNX1 defects. Characterisation of the transcription factor defects that give rise to platelet function disorders, and of the genes that are differentially regulated as a result, are yielding insights into the roles of these genes in platelet formation and function.
Topics: Blood Platelet Disorders; Blood Platelets; Disease Susceptibility; Gene Expression Regulation; Germ-Line Mutation; Hemostasis; Humans; Structure-Activity Relationship; Thrombopoiesis; Transcription Factors
PubMed: 27450272
DOI: 10.1016/j.blre.2016.07.002 -
Hamostaseologie Feb 2024
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombosis
PubMed: 38417798
DOI: 10.1055/s-0044-1782593 -
Platelets May 2020Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known... (Review)
Review
Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.
Topics: Aged; Aging; Animals; Blood Platelet Disorders; Blood Platelets; Comorbidity; Humans; Inflammation; Oxidative Stress; Platelet Activation; Risk Factors; Signal Transduction; Thrombosis
PubMed: 31524038
DOI: 10.1080/09537104.2019.1665641