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Blood Nov 2020Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill...
Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, coexisting symptoms, first-line laboratory workup, and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are: to rule thrombotic thrombocytopenic purpura (TTP) in or out, with urgency, using ADAMTS13 activity testing; to consider alternative disorders with features of TMA (preeclampsia/eclampsia; hemolysis elevated liver enzymes low platelets syndrome; antiphospholipid syndrome); or, ultimately, to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS; a diagnosis of exclusion). Although they are rare, diagnosing TTP and aHUS associated with pregnancy, and postpartum, is paramount as both require urgent specific treatment.
Topics: ADAMTS13 Protein; Disease Management; Female; Humans; International Agencies; Pregnancy; Pregnancy Complications; Research Report; Thrombotic Microangiopathies
PubMed: 32808006
DOI: 10.1182/blood.2020005221 -
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 -
Signal Transduction and Targeted Therapy Oct 2022Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the...
Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34 hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9 and HES1 cells from LinCD34CD45RA HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9LinCD34CD45RA HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9LinCD34CD45RA HSPCs was 3-fold higher than that of the CD9 counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9 HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9LinCD34CD45RA HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.
Topics: Bone Marrow; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombopoiesis; Transcriptome
PubMed: 36202780
DOI: 10.1038/s41392-022-01167-9 -
European Journal of Haematology Dec 2022In late February 2021, a prothrombotic syndrome was encountered for the first time in some of the recipients of ChAdOx1 CoV-19 vaccine (AstraZeneca, University of... (Review)
Review
In late February 2021, a prothrombotic syndrome was encountered for the first time in some of the recipients of ChAdOx1 CoV-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India). Since the hallmark of this syndrome is the development of thrombocytopenia and/or thrombosis between 4 and 42 days after receiving a COVID-19 vaccine, it was named vaccine-induced immune thrombotic thrombocytopenia (VITT). Other names include "vaccine-induced prothrombotic immune thrombocytopenia" and "thrombosis with thrombocytopenia syndrome" by the Centers for Disease Control and the Food and Drug Administration (FDA). VITT appears similar to heparin-induced thrombocytopenia in that "platelet activating" autoantibodies are produced in both these conditions due to prior exposure of COVID-19 vaccine and heparin respectively, in turn causing thrombotic complications and consumptive thrombocytopenia. In this article, recent advances in the understanding of pathobiology, clinical features, investigative work-up, and management of VITT are reviewed.
Topics: Humans; COVID-19; COVID-19 Vaccines; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 36030503
DOI: 10.1111/ejh.13855 -
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 -
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 -
Blood Dec 2022
Topics: Humans; Qi; Purpura, Thrombocytopenic, Idiopathic; Decitabine; Myeloid-Derived Suppressor Cells; Thrombocytopenia
PubMed: 36580341
DOI: 10.1182/blood.2022018373 -
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