Survey of Red Cell Parameters in 1600 United States Hospitals

Author(s):  
J. A. Koepke ◽  
J. Eilers
2020 ◽  
Vol 5 (1) ◽  
pp. 16-25
Author(s):  
Lixiang Chen ◽  
Jie Wang ◽  
Jing Liu ◽  
Hua Wang ◽  
Christopher D. Hillyer ◽  
...  

Abstract Liver, spleen, and bone marrow are 3 key erythropoietic tissues in mammals. In the mouse, the liver is the predominant site of erythropoiesis during fetal development, the spleen responds to stress erythropoiesis, and the bone marrow is involved in maintaining homeostatic erythropoiesis in adults. However, the dynamic changes and respective contributions of the erythropoietic activity of these tissues from birth to adulthood are incompletely defined. Using C57BL/6 mice, we systematically examined the age-dependent changes in liver, spleen, and bone marrow erythropoiesis following birth. In addition to bone marrow, the liver and spleen of newborn mice sustain an active erythropoietic activity that is gradually lost during first few weeks of life. While the erythropoietic activity of the liver is lost 1 week after birth, that of the spleen is maintained for 7 weeks until the erythropoietic activity of the bone marrow is sufficient to sustain steady-state adult erythropoiesis. Measurement of the red cell parameters demonstrates that these postnatal dynamic changes are reflected by varying indices of circulating red cells. While the red cell numbers, hemoglobin concentration, and hematocrit progressively increase after birth and reach steady-state levels by week 7, reticulocyte counts decrease during this time period. Mean cell volume and mean cell hemoglobin progressively decrease and reach steady state by week 3. Our findings provide comprehensive insights into developmental changes of murine erythropoiesis postnatally and have significant implications for the appropriate interpretation of findings from the variety of murine models used in the study of normal and disordered erythropoiesis.


Author(s):  
De las Nieves López MA ◽  
◽  
Robles Mateos C ◽  
Soria Cano JJ ◽  
Barón Fernandez O ◽  
...  

Background and Methods: Gliflozins are widely prescribed drugs in patients with type 2 diabetes. We pursue to explain abnormal increments in red cell parameters observed in this population, by means of a longitudinal study in 149 patients with a gliflozins exposure period of 12±6 months. Red cell parameters, HbA1c and other variables were recorded. Results: HbA1c fraction decreased (-0.5±1.3, 95% CI: -0.7 to -0.3, p<0.001), while mean hemoglobin (0.5±0.9, 95% CI: 0.3 to 0.6, P<0.001) and hematocrit (1.6±2.6, 95% CI: 1.2 to 2.0, P<0.001) increased. Mean (SD) hematocrit increased 2.7±1.9 in 112 patients, and decreased -1.7±1.5 in 37 (p<0.001 for subgroup differences). The larger increments in PCV were proportional to higher plasma fraction at baseline (p=0.009). Conclusion: Red cell parameters after gliflozins exposure tend to increase and may reach abnormally high thresholds in some patients with type 2 diabetes.


2016 ◽  
Vol 54 (1) ◽  
pp. 158-162 ◽  
Author(s):  
Matthew S. Karafin ◽  
Arun K. Singavi ◽  
Mehraboon S. Irani ◽  
Kathleen E. Puca ◽  
Lisa Baumann Kreuziger ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2613-2613
Author(s):  
K. Jang ◽  
Richard A. Wells ◽  
Alden Chesney ◽  
Marciano D. Reis ◽  
J. Friedlich ◽  
...  

Abstract The incidence of MDS is estimated to be 20–50 per 100,000 per year in people 60 years or older. However, the prevalence of this disease has not been determined. In an analysis of data from the National Health and Nutrition Examination Survey (NHANES), the overall prevalence of anaemia in persons 65 years and over in the U.S.A. was estimated to be 10.6% (2.0% for severe anemia, defined as hgb < 110 g/L). Patients with ‘unexplained anaemia’ (UA) accounted for 33.3% of all cases; of these, at least one peripheral blood feature suggesting MDS was present in 17.2%, representing 5.8% of the total anaemic population. To further refine this estimate, we evaluated the frequency of confirmed and suspected MDS diagnoses in a 4 year retrospective survey of bone marrows (BM) done at a single tertiary care institution to investigate unexplained uni, bi or tri-cytopenias. Methods: Only bone marrows performed to investigate unexplained cytopenia(s) were included. We excluded all outside referrals and bone marrows done for staging or remission assessment in patients with preexisting or strongly suspected hemato-lymphoid diagnoses. Electronic charts were reviewed for possible concurrent confounding risk factors such as nutritional deficiencies, hypothyroidism, renal insufficiency, malignancies or inflammatory/infectious conditions. Selected hematologic parameters such as mean corpuscular volume (MCV), red cell distribution width (RDW), hemoglobin (hgb), reticulocyte count etc. at time of bone marrow were recorded. Marrow reports were graded as confirmed (FAB or WHO classification) or suspected MDS, non-diagnostic, normal or other. Results: 322/2267 (14%) bone marrows met our inclusion criteria. The median age at BM was 70 yrs with 65% > age 65. Reasons for undergoing BM included anemia (33.5%), thrombocytopenia (9.0%), neutropenia (7.4%), >1 cytopenia (44.7%) and other (5.3%). One hundred and fifty five (48.4%) had concurrent risk factors for cytopenias that included nutritional deficiencies (8.4%), hypothyroidism (7.7%), renal insufficiency (42.6%), cancer (27%), infection and chronic inflammation (35%). Overall, 21% of all BM had confirmed MDS, 13% suspected MDS. Excluding patients with confounding risk factors, 24% (31% age > 65) had confirmed and 15% (18% age > 65) had suspected MDS. Of red cell parameters (hgb, MCV and RDW ), only the MCV was predictive of MDS in patients without risk factors, p=0.031. Overall, of 72 patients aged > 65 with UA as defined by NHANES, 35% had confirmed MDS, and 15% had suspected MDS. Conclusions: In patients with unexplained anaemia who undergo BM evaluation, the frequency of confirmed and suspected MDS is high (19%), and increases with age > 65 (50%). This figure is significantly higher than the estimate of 17.2% derived from analysis of the NHANES data and, since it is based upon histopathological analysis of BM rather than indirect evidence from blood counts, may be more accurate. Extrapolation to the Canadian and U.S. populations leads to an estimated prevalence of MDS of over 21,000 cases in people >65 in Canada, and over 210,000 in the U.S. Notwithstanding the limitations of this retrospective study, the potential impact of new MDS therapeutics, both on disease and pharmaco-economic burden may therefore be much greater than hitherto anticipated. With an aging population, more accurate prospective incidence and prevalence data for MDS are needed.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 75-75
Author(s):  
Anne-Laure Talbot ◽  
Grant C. Bullock ◽  
Lorrie L Delehanty ◽  
Adam Goldfarb

Abstract Abstract 75 Erythropoiesis is a complex developmental program regulated in part by erythropoietin (EPO) and iron levels. We have previously shown that erythroid iron deprivation causes diminished enzymatic activity of the multifunctional aconitase proteins (Bullock et al., ASH 2007 #707). In addition, pharmacological inhibition of aconitase impairs erythroid growth and maturation in a lineage-selective manner without compromising ATP levels, suggesting a novel, non-metabolic regulatory role for aconitase in erythropoiesis (Talbot et al., ASH 2008 #3865). The nature of this regulatory role was addressed in the present study by examining the connection between aconitase activity and erythroid signal transduction. The impact of aconitase inhibition by fluoroacetate (FA) on several candidate pathways was assessed in primary human erythroid progenitors by standard immunoblotting. This approach consistently implicated the mitogen activated protein kinases (MAPKs) ERK1/2, whose phosphorylation was strongly induced both at early (30 minutes) and late (4 days) time points. In addition, phosphorylation of the other MAPKs p38 and JNK was unchanged, ruling out a non-specific stress response. To determine why aconitase inhibition augmented ERK1/2 phosphorylation, the effects of FA were determined on the upstream kinases MEK1/2. Surprisingly, phosphorylation of MEK1/2 showed no changes at earlier time points (up to 24 hours) and decreases at later time points (2–4 days). Activation of ERK/1/2 in the absence of MEK1/2 activation suggests an unconventional pathway in which aconitase regulates dephosphorylation, scaffolding, or subcellular localization. The inhibition of erythropoiesis by FA could result from increased ERK1/2 activity or diminished MEK1/2 activity. The first mechanism predicts phenotypic rescue by addition of MEK inhibitor (U0126), whereas the second mechanism predicts increased inhibition. In fact, U0126 alone recapitulated the anti-proliferative and anti-differentiative effects of FA on primary erythroid cultures, and the combination of U0126 and FA caused increased inhibition of growth and differentiation, arguing in favor of MEK1/2 repression as a mechanism for FA. Our findings establish that aconitase modulates signaling through the MEK-ERK pathway, perturbation of which may block erythropoiesis. To expand our studies on the in vivo role of aconitase in erythropoiesis, the impact of aconitase blockade was assessed in two additional murine models: phenylhydrazine (PHZ)-induced stress erythropoiesis and Polycythemia vera (PV). In both systems, erythropoiesis was found to be extremely sensitive to aconitase blockade. In the first system, adult C57Bl/6 female mice were treated with continuous FA infusion plus bolus intraperitoneal PHZ. FA-treated mice developed a much more severe anemia in response to PHZ than did non-FA-treated mice despite receiving 50% less PHZ. Their anemia showed a lower nadir (red cell count of 3.56 M/ul vs. 4.75 M/ul, p=0.0013, n=6) and a more prolonged trough. Their reticulocytosis was delayed and diminished. In the second system, PV female mice carrying one copy of the JAK2 V617F allele were treated with continuous FA infusion. Decreased red indices were observed by day 11 of treatment, with a decline in hematocrit from 51.3% to 42.5% in PV mice (p=0.0002, n=4), compared with a decline from 44.6% to 37.9% in wild type mice (p=0.04, n=4). No effects were observed on platelet and leukocyte counts. Interestingly, the rate of decrease of the red cell parameters was greater in the PV mice, suggesting that erythropoiesis driven by JAK2 V617F is highly responsive to changes in aconitase activity levels. We conclude that aconitase functions as a modifier of erythroid signaling to regulate proliferation and differentiation. Indeed, our results indicate that aconitase activity regulates steady state, stress, and JAK2 V617F-driven erythropoiesis, most likely through its novel modulation of MEK-ERK signaling. This novel function may provide an alternate targeting strategy in the treatment of Polycythemia vera. Disclosures: No relevant conflicts of interest to declare.


Hemoglobin ◽  
2013 ◽  
Vol 38 (1) ◽  
pp. 56-59 ◽  
Author(s):  
Bayan Al-Dabbagh ◽  
Saad Shawqi ◽  
Javed Yasin ◽  
Awad Al Essa ◽  
Nico Nagelkerke ◽  
...  

2021 ◽  
Vol 52 (1) ◽  
pp. 13
Author(s):  
K. H. B. P. Fernandopulle ◽  
H. M. J. P. Herath ◽  
L. D. Udawatta ◽  
P. M. N. K. Senarathna

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