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Hemato, Volume 4, Issue 4 (December 2023) – 7 articles

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20 pages, 1897 KiB  
Review
The Role of Platelet Molecules in Risk Stratification of Patients with COVID-19
by Lívia de Oliveira Sales, Lais Lacerda Brasil de Oliveira, Jean Breno Silveira da Silva, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, Raquel Carvalho Montenegro and Caroline Aquino Moreira-Nunes
Hemato 2023, 4(4), 364-383; https://doi.org/10.3390/hemato4040029 - 30 Nov 2023
Cited by 1 | Viewed by 796
Abstract
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and is responsible for Coronavirus disease (COVID-19). Despite being well tolerated by most patients, a fraction of cases evolve into a potentially fatal condition requiring intensive care. In addition [...] Read more.
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and is responsible for Coronavirus disease (COVID-19). Despite being well tolerated by most patients, a fraction of cases evolve into a potentially fatal condition requiring intensive care. In addition to respiratory complications, several studies have reported cases of patients who developed intense thrombosis, including acute myocardial infarction and ischemic stroke, as well as the presence of elevated coagulation markers. Evidence has shown that the virus can interact directly with platelets and modulate their thrombotic and inflammatory functions, with significant prognostic implications. It is important to highlight that the emerging literature shows that when hyperactive these cells can act as pro-viral infections both in transporting their particles and in increasing inflammation, leading to a hyperinflammatory state and consequent clinical worsening. In this review, we searched for studies available in public databases and discussed the interaction of platelet biomarkers in the pathogenesis of COVID-19. In this context, understanding the mechanism of SARS-CoV-2 and these cells in different clinical conditions could help us to understand the coagulation and inflammation profiles of critically ill patients with the disease, guiding faster clinical management and enabling the reuse and targeting of more efficient therapies. Full article
(This article belongs to the Section Coagulation)
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14 pages, 18830 KiB  
Article
Fibril-Forming Organelles in Mesangial Cells in Renal Biopsies from Patients with Light-Chain-Associated Amyloidosis
by Guillermo A. Herrera, Jiamin Teng, Chun Zeng, Luis Del Pozo-Yauner, Bing Liu and Elba A. Turbat-Herrera
Hemato 2023, 4(4), 350-363; https://doi.org/10.3390/hemato4040028 - 23 Nov 2023
Viewed by 672
Abstract
The process of light-chain-associated amyloid (AL-Am) fibril formation in unique organelles (fibril-forming organelles) with lysosomal features has been documented in vitro in renal mesangial cells incubated with amyloidogenic light chains using electron microscopy and lysosomal gradient centrifugation to visualize intricate interactions between monoclonal [...] Read more.
The process of light-chain-associated amyloid (AL-Am) fibril formation in unique organelles (fibril-forming organelles) with lysosomal features has been documented in vitro in renal mesangial cells incubated with amyloidogenic light chains using electron microscopy and lysosomal gradient centrifugation to visualize intricate interactions between monoclonal light chains and endosomes/lysosomes. It is important to determine whether this process also occurs in vivo in the human renal mesangium. The present study analyzes 13 renal biopsies from patients with renal AL-amyloidosis and utilizes ultrastructural labeling techniques to define the nature and function of these organelles. Organelles were labeled for lysosomal-associated membrane protein (LAMP) and CD-68 (a macrophage marker). Furthermore, lambda was also localized inside these structures in transformed mesangial cells with a macrophage phenotype. These 11 cases from renal biopsies with a diagnosis of AL-amyloidosis (5 kappa and 8 lambda light-chain-associated) were examined ultrastructurally. All of the cases exhibited numerous fibrils forming organelles in approximately 40–50% of the remaining mesangial cells. All of the cases revealed mesangial cells engaged in active amyloidogenesis. Fibril-forming organelles are organelles with morphological/immunohistochemical and biochemical characteristics of lysosomes but with a unique, peculiar morphology. Five cases of other glomerular disorders used as controls were also carefully scrutinized for fibril-forming organelles and failed to show any. In the AL-amyloid renal cases, there was an intricate interaction between the fibril-forming organelles and lambda-/kappa-containing amyloid fibrils, supporting the notion that the monoclonal light chains participated in their formation. Full article
(This article belongs to the Section Plasma Cell Disorders)
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19 pages, 2035 KiB  
Systematic Review
Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
by Karina P. Verma, Rebecca Steuer and Camille V. Edwards
Hemato 2023, 4(4), 331-349; https://doi.org/10.3390/hemato4040027 - 01 Nov 2023
Viewed by 1193
Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant plasma cell disorder with an etiology that is incompletely understood. Modifiable risk factors and genetic predispositions likely interact to increase MGUS risk in specific individuals and populations. Identifying geographic prevalence patterns and modifiable risk [...] Read more.
Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant plasma cell disorder with an etiology that is incompletely understood. Modifiable risk factors and genetic predispositions likely interact to increase MGUS risk in specific individuals and populations. Identifying geographic prevalence patterns and modifiable risk factors is critical for understanding the etiology of MGUS. The aim of this review was to outline original research on MGUS prevalence across geographic locations and modifiable risk factors. We conducted a systematic review of 39 eligible studies from PubMed®, Embase®, and Web of Science® written in English and published by February 2023. Our protocol was registered in accordance with PROSPERO guidelines. Studies were synthesized using Research Electronic Data Capture and appraised using the National Heart, Lung, and Blood Institute study quality assessment tools. The prevalence of MGUS ranged from 0.24% to 9% across geographic locations. Modifiable risk factors for MGUS include infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors, environmental exposures, and ionizing radiation. Therefore, the development of MGUS may be related to chronic antigenic stimulation and genetic aberrations that promote clonal proliferation of plasma cells. Prospective studies assessing gene–environment interactions are needed to further define risk factors for MGUS and inform screening and preventative strategies. Full article
(This article belongs to the Section Plasma Cell Disorders)
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10 pages, 490 KiB  
Review
The Role of PET in the Diagnosis and Disease Activity Assessment in Large Vessel Vasculitis
by Chiara Marvisi, Elena Galli, Caterina Ricordi, Rexhep Durmo, Massimo Roncali, Francesco Muratore, Carlo Salvarani and Annibale Versari
Hemato 2023, 4(4), 321-330; https://doi.org/10.3390/hemato4040026 - 30 Oct 2023
Viewed by 857
Abstract
The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (18F-FDG PET) in the diagnosis of large vessel vasculitis (LVV) is well established. It permits us to assess the extent and the grade of vascular involvement and to rule out the other causes in clinical [...] Read more.
The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (18F-FDG PET) in the diagnosis of large vessel vasculitis (LVV) is well established. It permits us to assess the extent and the grade of vascular involvement and to rule out the other causes in clinical scenarios characterized by less specific symptoms. The advantages of 18F-FDG PET are far less clear in monitoring disease activity over time. Studies looking for the role of 18F-FDG PET as a potential biomarker had conflicting results and whether and when to repeat it during follow-up is based on clinical experience. A comprehensive assessment, including clinical, laboratory and morphological imaging is still required to monitor patients with large-vessel vasculitis over time. The aim of this review is to present more recent data about the utility of 18 F-FDG PET in the diagnosis and follow-up of LVV. Full article
(This article belongs to the Section Radiolabeled Blood Elements and Other Imaging Modalities)
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10 pages, 941 KiB  
Case Report
Methotrexate-Induced Subacute Combined Degeneration in Acute Lymphoblastic Leukemia with CNS Relapse May Be Reversible
by David Bared Dukenik, Deborah Soong, Wenhui Li, Ellen Madarang, Justin Watts and Justin Taylor
Hemato 2023, 4(4), 311-320; https://doi.org/10.3390/hemato4040025 - 16 Oct 2023
Viewed by 2036
Abstract
We describe a case of a female patient with acute lymphoblastic leukemia treated with high-dose systemic methotrexate and intrathecal methotrexate for leukemic relapse of the central nervous system. She developed complete bilateral lower-limb paralysis that was not attributable to any other cause. She [...] Read more.
We describe a case of a female patient with acute lymphoblastic leukemia treated with high-dose systemic methotrexate and intrathecal methotrexate for leukemic relapse of the central nervous system. She developed complete bilateral lower-limb paralysis that was not attributable to any other cause. She was treated with folic acid, vitamin B12, methionine, S-adenosylmethionine, leucovorin, and dextromethorphan. After a 3-month period of paraplegia, she began to slowly recover motor function. She can now ambulate with assistance and continues to improve. There is a paucity of literature on methotrexate-induced subacute combined degeneration, which is typically described as irreversible. In addition to reporting our unique case, we review the published literature and call for more awareness and research in this area. Full article
(This article belongs to the Section Leukemias)
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10 pages, 1162 KiB  
Article
Coagulation Profiles in Humans Exposed to Exertional Hypobaric Decompression Stress Determined by Calibrated Automated Thrombogram
by Leigh A. Madden, Rebecca V. Vince, Victoria C. Edwards, Vivienne M. Lee and Desmond M. Connolly
Hemato 2023, 4(4), 301-310; https://doi.org/10.3390/hemato4040024 - 01 Oct 2023
Viewed by 787
Abstract
The blood coagulation response to decompression stress in humans has yet to be fully investigated. Here we utilised calibrated automated thrombogram (CAT) on samples from healthy volunteers exposed to decompression stress to investigate real-time thrombin generation. To induce decompression stress, fifteen apparently healthy [...] Read more.
The blood coagulation response to decompression stress in humans has yet to be fully investigated. Here we utilised calibrated automated thrombogram (CAT) on samples from healthy volunteers exposed to decompression stress to investigate real-time thrombin generation. To induce decompression stress, fifteen apparently healthy males (age 20–50 yr) were exposed to two consecutive ascents to 25,000 ft for 60 min (1st ascent) and then 90 min (2nd ascent) while breathing 100% oxygen. Citrated blood samples were taken prior to exposure (T0), following the 2nd ascent (T8) and at 24 h (T24). Thrombin generation curves were obtained using ThrombinoscopeTM. Parameters determined were lag time (LAG), time to peak (TTP), peak thrombin (PEAK), endogenous thrombin potential (ETP) and velocity index (VEL). Of the 15 subjects, 12 had validated coagulation profiles. TTP and ETP showed no significant differences. However, there was a significant increase in VEL from T0 to T8 (p = 0.025) and from T8 to T24 (p = 0.043). A non-significant trend of an overall increase in PEAK was also observed from T0 to T8 (p = 0.069) and from T8 to T24 (p = 0.098). PEAK and VEL were found to be correlated. Taken together, these two parameters suggest an overall shift towards a more procoagulant profile following hypobaric stress. Full article
(This article belongs to the Section Coagulation)
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16 pages, 7345 KiB  
Review
Imaging of Vascular Graft/Endograft Infection with Radiolabeled White Blood Cell Scan and [18F]FDG PET/CT
by Ringo Manta, Chiara Lauri, Maurizio Taurino and Alberto Signore
Hemato 2023, 4(4), 285-300; https://doi.org/10.3390/hemato4040023 - 22 Sep 2023
Viewed by 948
Abstract
Diagnosis of vascular graft/endograft infection (VGEI) is a challenge for clinicians due to the heterogeneity of clinical presentation and the complexity of its management. Microbiological culture is the gold standard, but it often fails to isolate the causative microorganism. A non-invasive imaging approach [...] Read more.
Diagnosis of vascular graft/endograft infection (VGEI) is a challenge for clinicians due to the heterogeneity of clinical presentation and the complexity of its management. Microbiological culture is the gold standard, but it often fails to isolate the causative microorganism. A non-invasive imaging approach is therefore needed to assess VGEI. CTA is currently the first-choice imaging modality. Nuclear medicine techniques are recommended in case of negative or doubtful CTA results with persisting clinical suspicion. This review aims to summarize data from original studies published in the last decades regarding the role of both white blood cell (WBC) scans and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT), their respective diagnostic performances, and their integration into the diagnostic approach for patients with a suspicion of VGEI. Full article
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