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Journal of Thoracic Disease Oct 2015The red blood cell distribution width (RDW) is a rather simple measure of red blood cell (RBC) size heterogeneity (i.e., anisocytosis), which is easily calculated by... (Review)
Review
BACKGROUND
The red blood cell distribution width (RDW) is a rather simple measure of red blood cell (RBC) size heterogeneity (i.e., anisocytosis), which is easily calculated by dividing the standard deviation (SD) of erythrocyte volumes for the mean corpuscular volume (MCV). Emerging evidence suggests that, besides RBC abnormalities, many human disorders may be frequently associated with a high degree of anisocytosis.
METHODS
In this narrative review, we analyzed the current scientific literature about the putative role and the potential epidemiologic association between RDW and cardiovascular diseases. The findings of the most representative epidemiological studies were summarized and discussed.
RESULTS
Overall, considerable and convincing evidence has been brought that an increased RDW value is associated with acute coronary syndrome (ACS) [including acute myocardial infarction (AMI)], ischemic cerebrovascular disease (including stroke), peripheral artery disease (PAD), as well as with atrial fibrillation (AF), heart failure (HF) and hypertension. Higher anisocytosis also significantly and independently predicts adverse outcomes in patients with these conditions.
CONCLUSIONS
Although the role of anisocytosis in the pathogenesis of cardiovascular diseases remains uncertain, the considerable evidence available so far suggests that the clinical use of RDW may be broadened beyond the conventional boundaries of erythrocyte disorders, in particular for assisting the diagnosis and prognostication of patients with ACS, ischemic cerebrovascular disease, PAD, HF and AF.
PubMed: 26623117
DOI: 10.3978/j.issn.2072-1439.2015.10.04 -
Blood Advances Dec 2021β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet...
β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.
Topics: Blood Platelets; Humans; Megakaryocytes; Thrombocytopenia; Tubulin
PubMed: 34516618
DOI: 10.1182/bloodadvances.2020004057 -
Frontiers in Pediatrics 2023Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well...
INTRODUCTION
Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children.
METHODS
We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children.
RESULTS
Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters.
CONCLUSION
Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.
PubMed: 37425266
DOI: 10.3389/fped.2023.1177048 -
Journal of Comparative Pathology Apr 2023A 12-year-old male neutered Australian Shepherd Dog was presented to Charlotte Animal Referral & Emergency with a history of a thoracic mass. On physical examination,...
A 12-year-old male neutered Australian Shepherd Dog was presented to Charlotte Animal Referral & Emergency with a history of a thoracic mass. On physical examination, physiological parameters were within the normal ranges, and a complete haemogram and serum biochemistry profile were unremarkable except for mild thrombocytopenia. A computed tomography scan revealed a 21 × 15 × 12.7 cm thoracic mass encompassing the cranial mediastinum and extending to the right caudal thorax. The mass was surgically removed and histopathological evaluation revealed that it comprised remnants of the thymus and a neoplasm composed of large blood-filled vascular spaces lined by a single layer of endothelial cells with mild anisocytosis and anisokaryosis. The neoplastic cells had diffuse strong immunolabeling for endothelial cell marker CD31. Multifocally, there were large cystic degenerated areas of thymic tissue lined by plump cytokeratin AE1/AE3-positive epithelial cells. Based on these findings, a diagnosis of thymic cavernous haemangioma (CH) was made. Thymic CH is rare in animals, with the only reported case in a cross bred cow. To our knowledge, this is the first case of a thymic CH in a dog.
Topics: Male; Female; Cattle; Dogs; Animals; Endothelial Cells; Australia; Hemangioma, Cavernous; Dog Diseases; Tomography, X-Ray Computed; Cattle Diseases
PubMed: 36931010
DOI: 10.1016/j.jcpa.2023.02.001 -
Kardiologia Polska 2022
The relationship between anisocytosis, quantitative and qualitative characteristics of coronary atherosclerosis, and major adverse cardiac events in patients with coronary artery disease: Rationale and study design.
Topics: Coronary Angiography; Coronary Artery Disease; Humans; Myocardial Infarction; Risk Factors
PubMed: 35475462
DOI: 10.33963/KP.a2022.0111 -
Pathogens & Immunity 2017Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that...
BACKGROUND
Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy.
METHODS
We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models.
RESULTS
The median age (IQR) for the cohort at enrollment was 46 (40-53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9-14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all < 0.05). At baseline, RDW weakly correlated with C-reactive protein (r = 0.196), d-dimer (r = 0.214), fibrinogen (r = 0.192), IL-6 (r = 0.257), CD4+DR+38+ T cells (r = 0.195), and CD4+PD1+ T cells (r = 0.227), all < 0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin ( = 0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points ( = 0.05).
CONCLUSION
In this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy.
PubMed: 28713869
DOI: 10.20411/pai.v2i1.199 -
World Journal of Gastroenterology Jul 2017The red blood cell distribution width (RDW) is a routinely measured and automatically reported blood parameter, which reflects the degree of anisocytosis. Recently, the... (Review)
Review
The red blood cell distribution width (RDW) is a routinely measured and automatically reported blood parameter, which reflects the degree of anisocytosis. Recently, the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases, sepsis, cancers, leukemia, renal dysfunction and respiratory diseases. A myriad of factors, most of which ill-defined, have an impact on the red cell population dynamics (., production, maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review, we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data, RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers (., C reactive protein, erythrocyte sedimentation rate, and platelet count) and current disease severity indices used in clinical practice.
Topics: Biomarkers; Blood Cell Count; Blood Sedimentation; C-Reactive Protein; Endoscopy; Erythrocyte Indices; Erythrocytes; Gastrointestinal Diseases; Humans; Inflammation; Prognosis; Severity of Illness Index; Survival Rate
PubMed: 28785142
DOI: 10.3748/wjg.v23.i27.4879 -
Frontiers in Bioscience (Elite Edition) Jul 2023The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase... (Observational Study)
Observational Study
Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score.
BACKGROUND
The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS).
MATERIALS AND METHODS
Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.
RESULTS
We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS ( 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 7.9 months; median OS (mOS): 33.7 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; < 0.001, respectively), while the impact on PFS resulted in borderline significance.
CONCLUSIONS
Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.
Topics: Humans; Carcinoma, Renal Cell; Vascular Endothelial Growth Factor A; Prognosis; Kidney Neoplasms; Erythrocytes; Hemoglobins
PubMed: 37743233
DOI: 10.31083/j.fbe1503020 -
Annals of Translational Medicine Jul 2017Red blood cell distribution width (RDW) is a simple, inexpensive, routinely measured and automatically reported blood test parameter, which reflects the degree of... (Review)
Review
Red blood cell distribution width (RDW) is a simple, inexpensive, routinely measured and automatically reported blood test parameter, which reflects the degree of anisocytosis of red blood cells in peripheral blood. RDW was found to be associated with and retain clinical significance for assessing disease severity and outcomes in a number of hematological and solid malignancies. Motley of interacting clinical and biochemical factors have an impact on the red cell population biology. Malignancies per se can act as a causative factor, or anisocytosis may develop as a result of chronic inflammation. RDW has also been shown to be affected by nutritional status, which is typically deranged in malignancies. RDW is shown to be a clinically useful marker of disease severity and level of fibrosis in liver cirrhosis of various causes such as hepatitis B, hepatitis C and non-alcoholic fatty liver disease. Whether liver cirrhosis patients with higher RDW are at increased risk of hepatocellular cancer is yet to be determined, but several lines of evidence confirm that RDW has clinical significance in hepatocellular carcinoma (HCC). In this review, we specifically discuss the current literature about the association between RDW and HCC. The available evidences were summarized and the potential underlying mechanisms were analyzed.
PubMed: 28758097
DOI: 10.21037/atm.2017.06.30 -
Journal of Veterinary Internal Medicine Jan 2019Megaloblastic, nonregenerative anemia is a well-known consequence of cobalamin or folate deficiencies in humans but is not recognized in hypocobalaminemic or...
BACKGROUND
Megaloblastic, nonregenerative anemia is a well-known consequence of cobalamin or folate deficiencies in humans but is not recognized in hypocobalaminemic or hypofolatemic dogs. Establishment of relationships between hypocobalaminemia or hypofolatemia and hematologic disease would encourage vitamin B testing, and potentially supplementation, in anemic dogs.
OBJECTIVES
To determine the prevalence of anemia in hypocobalaminemic or hypofolatemic dogs and to report the prevalence of hypocobalaminemia and hypofolatemia and nonregenerative anemia, macrocytosis, and anisocytosis in anemic dogs.
ANIMALS
One hundred and fourteen client-owned dogs with known serum cobalamin and folate concentrations and CBCs and 42 client-owned anemic dogs.
METHODS
Retrospective comparison of anemia prevalence in hypocobalaminemic or hypofolatemic and normocobalaminemic or normofolatemic dogs was performed. Prospective measurement of erythrocyte variables and cobalamin and folate concentrations in anemic dogs was carried out; relationships among hypocobalaminemia and regenerative status, mean corpuscular volume, and red cell distribution width were evaluated.
RESULTS
Significant differences in prevalence of anemia between hypocobalaminemic (36%) and normocobalaminemic dogs (26%; P = .23) or between hypofolatemic (31%) and normofolatemic dogs (30%; P = .99) were not detected. Between hypocobalaminemic and normocobalaminemic dogs, no significant differences in prevalence of nonregenerative anemia (69% vs 63%; P = .65), macrocytosis (17% vs 0%; P = .53), or anisocytosis (28% vs 0%; P = .14) were detected. Anemic dogs had high prevalence of vitamin B deficiencies (nonregenerative: 64% hypocobalaminemic, 18% hypofolatemic; regenerative: 57% hypocobalaminemic, 21% hypofolatemic).
CONCLUSIONS AND CLINICAL IMPORTANCE
The association between cobalamin and folate deficiencies and macrocytic, nonregenerative anemia established in humans is not routinely present in dogs.
Topics: Anemia; Animals; Case-Control Studies; Dog Diseases; Dogs; Female; Folic Acid; Folic Acid Deficiency; Male; Prevalence; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 30499147
DOI: 10.1111/jvim.15348