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"Hematologic Diseases - blood"
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Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization
Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.
Journal Article
A large dataset of white blood cells containing cell locations and types, along with segmented nuclei and cytoplasm
Accurate and early detection of anomalies in peripheral white blood cells plays a crucial role in the evaluation of well-being in individuals and the diagnosis and prognosis of hematologic diseases. For example, some blood disorders and immune system-related diseases are diagnosed by the differential count of white blood cells, which is one of the common laboratory tests. Data is one of the most important ingredients in the development and testing of many commercial and successful automatic or semi-automatic systems. To this end, this study introduces a free access dataset of normal peripheral white blood cells called Raabin-WBC containing about 40,000 images of white blood cells and color spots. For ensuring the validity of the data, a significant number of cells were labeled by two experts. Also, the ground truths of the nuclei and cytoplasm are extracted for 1145 selected cells. To provide the necessary diversity, various smears have been imaged, and two different cameras and two different microscopes were used. We did some preliminary deep learning experiments on Raabin-WBC to demonstrate how the generalization power of machine learning methods, especially deep neural networks, can be affected by the mentioned diversity. Raabin-WBC as a public data in the field of health can be used for the model development and testing in different machine learning tasks including classification, detection, segmentation, and localization.
Journal Article
Hematological features of persons with COVID-19
We studied admission and dynamic demographic, hematological and biochemical co-variates in 1449 hospitalized subjects with coronavirus infectious disease-2019 (COVID-19) in five hospitals in Wuhan, Hubei province, China. We identified two admission co-variates: age (Odds Ratio [OR] = 1.18, 95% Confidence Interval [CI] [1.02, 1.36]; P = 0.026) and baseline D-dimer (OR = 3.18 [1.48, 6.82]; P = 0.003) correlated with an increased risk of death in persons with COVID-19. We also found dynamic changes in four co-variates, Δ fibrinogen (OR = 6.45 [1.31, 31.69]; P = 0.022), Δ platelets (OR = 0.95 [0.90–0.99]; P = 0.029), Δ C-reactive protein (CRP) (OR = 1.09 [1.01, 1.18]; P = 0.037), and Δ lactate dehydrogenase (LDH) (OR = 1.03 [1.01, 1.06]; P = 0.007) correlated with an increased risk of death. The potential risk factors of old age, high baseline D-dimer, and dynamic co-variates of fibrinogen, platelets, CRP, and LDH could help clinicians to identify and treat subjects with poor prognosis.
Journal Article
Central venous catheter-associated bloodstream infection and colonisation of insertion site and catheter tip. What are the rates and risk factors in haematology patients
Skin colonisation is an important source for central venous catheter (CVC) colonisation and infection. This study intended to identify risk factors for skin colonisation prior to CVC placement (baseline colonisation) and within 10 days after CVC insertion (subsequent colonisation), for CVC-tip colonisation and for bloodstream infection (BSI). Within a randomised clinical trial, data of 219 patients with haematological malignancies and inserted CVC (with a total of 5,501 CVC-days and 4,275 days at risk) in two university hospitals were analysed. Quantitative skin cultures were obtained from the insertion site before CVC placement and at regular intervals afterwards. CVC-tip cultures were taken on CVC removal and data collection was performed. Statistical analysis included linear and logistic regression models. Age was an independent risk factor for colonisation prior to CVC placement (baseline colonisation). Independent risk factors for subsequent colonisation were baseline colonisation and male gender. High level of subsequent skin colonisation at the insertion site was a predictor of CVC-tip colonisation, and a predictor of BSI. High level of skin colonisation predicts catheter tip colonisation and possibly subsequent infection. Sustained reduction of bacterial growth at the CVC insertion site is therefore indispensable. Male patients are at particular risk for skin colonisation and may be a target population for additional insertion-site care before and during catheterisation.
Journal Article
Is COVID-19 a New Hematologic Disease?
SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 (Covid-19). Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications. Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies. A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.
Journal Article
Genome-wide association study of hematological and biochemical traits in a Japanese population
Naoyuki Kamatani and colleagues report genome-wide association studies for 8 hematological traits and 12 biochemical traits in a Japanese population.
We report genome-wide association studies for hematological and biochemical traits from ∼14,700 Japanese individuals. We identified 60 associations for 8 hematological traits and 29 associations for 12 biochemical traits at genome-wide significance levels (
P
< 5 × 10
−8
). Of these, 46 associations were new to this study and 43 replicated previous reports. We compared these associated loci with those reported in similar GWAS in European populations. When the minor allele frequency was >10% in the Japanese population, 32 (94.1%) and 31 (91.2%) of the 34 hematological loci previously reported to be associated in a European population were replicated with
P
-values less than 0.05 and 0.01, respectively, and 31 (73.8%) and 27 (64.3%) of the 42 European biochemical loci were replicated.
Journal Article
Bone Marrow and Peripheral Blood Findings in Patients Infected by SARS-CoV-2
Abstract
Objectives
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with diverse clinical, including hematologic, abnormalities. We describe peripheral blood and bone marrow findings in deceased and living patients with COVID-19.
Methods
We examined bone marrows from 20 autopsies and 2 living patients with COVID-19 using H&E-stained slides and immunohistochemical stains. Clinical history and laboratory values were reviewed. HScore was calculated to estimate risk of hemophagocytic lymphohistocytosis (HLH).
Results
The deceased patients included 12 men and 8 women (aged 32 to >89 years; median, 63 years). Hematologic abnormalities included frequent neutrophilic leukocytosis, lymphopenia, anemia, and thrombocytopenia; one patient showed striking erythrocytosis. The bone marrows were all normocellular to hypercellular, most showing maturing trilineage hematopoiesis with myeloid left shift. In all 19 evaluable bone marrows, hemophagocytic histiocytes were identified. The HScore for secondary HLH ranged from 35 to 269 (median, 125; >169 in 5 patients). Coinfections were identified in 6 patients. In 2 living patients, bone marrow showed maturing trilineage hematopoiesis, including one showing few hemophagocytic histiocytes.
Conclusions
Peripheral blood from deceased patients with COVID-19 frequently showed neutrophilic leukocytosis, lymphopenia, and, rarely, secondary polycythemia; hemophagocytosis was common in their bone marrow. Consistent with other studies, we provide histopathologic evidence of secondary HLH development in patients with COVID-19.
Journal Article
Hematologic disorders associated with COVID-19: a review
Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.
Journal Article
Hematological abnormalities and associated factors among patients with thyroid hormone dysfunction at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia
Thyroid hormones substantially influence the metabolism and production of blood cells; as a result, blood disorders are frequently seen among patients with thyroid hormone disorders. Therefore, this study aimed to assess hematological abnormalities and associated factors among patients with thyroid hormone dysfunction.
A hospital-based cross-sectional study was conducted from March 12/03/2022 to May 26/05/2022 among consecutive selected 308 study participants at the University Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A structured questionnaire and data extraction sheet were used to collect socio-demographic and Clinical data, respectively. For complete blood cell count analysis venous blood was collected and analyzed by Beckman-coulter DXH-800 hematology analyzer. Data was entered by Epi data version 3.1 and analyzed by Stata version 14. Binary and multivariable logistic regressions were done to identify associated factors of hematological abnormality. A P-value less than 0.05 was considered statistically significant.
The overall magnitude of anemia, leukopenia, thrombocytopenia, thrombocytosis, leukocytosis, and polycythemia was 26.3%, 5.5%, 2.6%, 2.3%, 2.3%, and 1.3%, respectively. Hypothyroidism (AOR = 2, 95% CI:1.0-3.6), alcohol consumption (AOR = 4, 95% CI: 1.7-9.2), meat consumption (AOR = 4, 95% CI: 1.6-10.4), vegetable consumption (AOR = 2.5, 95% CI:1.1-5.5) and febrile illness (AOR = 2.6, 95% CI:1.3-5.4) were found to be associated with anemia.
Anemia was a moderate public health problem among thyroid dysfunction patients, mainly normocytic normochromic anemia was the most common type of anemia, leukopenia was second major hematological abnormality. Hypothyroidism, alcohol consumption, meat consumption, vegetable consumption, and febrile illness were associated with anemia. Thus, all patients with thyroid dysfunction should have regular anemia screenings, particularly those with important risk factors. This could aid in the early identification and efficient treatment of anemia, improving the patients' quality of life.
Journal Article