Age-related local versus systemic early phase wound healing dynamics following free gingival graft harvest.

Several herbal preparations are used to treat diabetes; however, their overall biochemical effects other than hypoglycemic effects are scanty. This study therefore was designed to evaluate the effect of methanolic extract of leaves and stem-bark of Adansonia digitata on biochemical indices of streptozotocin-induced diabetic rats. Sixty-three wistar rats were distributed into 9 groups of 7 each. The test animals were intraperitoneally administered with single dose of 50 mg/kg streptozotocin and monitored for 72 hours for development of hyperglycemia. Diabetic rats were treated in 12 h cycles for three weeks with 100 mg/kg, 200 mg/kg and 300 mg/kg of both leaves and stem-bark of Adansonia digitata methanolic extract and metformin (50 mg/kg). Non-diabetic control rats received a lacebo of distilled water. Group 1 served as normal control, group 2 served as diabetic control, while groups 4-9 were diabetic rats treated orally with methanolic leave and stem-bark extracts of Adansonia digitata (100 mg/kg, 200 mg/kg and 300 mg/kg) for 21days. Group 3 animals were diabetic rats treated with anti-diabetic drug (metformin 50 mg/kg). The levels of fasting blood sugar (FBS), electrolytes (Na+, K+, Cl-), Urea and creatinine Triglyceride (TG), Cholesterol (CHOL), thiobarbituric acid reactive substance (TBARS), White Blood Cell (WBC) count, Red Blood Cell (RBC) count, Haemoglobin (HGB), Hematocrit (HCT), Platelet (PLT), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), Mean Cell Haemoglobin Concentration (MCHC), Lymphocyte (LYM), aspartatate aminotransfrease (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), catalase (CAT) and superoxide dismutase (SOD) activities total, total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentrations were assayed. The results indicated that the concentrations of Na+, K+, Cl-, creatinine, urea TBARS, ALT, AST, ALB, CHOL and IB bilirubin were significantly (p<0.05) increased, while the levels of WBC, RBC, HGB, HCT, PLT, LYM, MCV SOD and CAT were reduced in the diabetic control (p<0.05). The Adansonia digitata methanolic leaves and stem-bark extract significantly increased WBC, RBC, HGB, HCT, PLT, MCV, LYM, TP, CAT and SOD activity and reduced the FBS, Na+, K+, Cl-, TBARS, ALT, AST, creatinine, urea and bilirubin concentrations significantly (p<0.05) compared to normal control. However, treatment with metformin showed slight modification in the changes observed compared to Adansonia digitata methanolic leaves and stem-bark extract. MCV and MCHC reduced non-significantly (p>0.05) in the diabetic animals as compared to the normal control and the extract-treated rats, while they increased non- significantly (p>0.05) in the test groups when compared to the diabetic control. Levels of TB, DB, and TG showed non-significant (p<0.05) increase in diabetic control, but treatment with extracts and metformin caused non-significant decrease (p<0.05). Diabetic control exhibited significantly (p<0.05) decreased ALB levels and non-significant TP decrease compared to normal control, while Adansonia digitata extracts and metformin significantly increased ALB and non-significantly increased TP levels compared to diabetic control. The study concluded that Adansonia digitata extracts reversed diabetes-induced oxidative stress in rat hepatocytes, potentially through beta cell regeneration or insulin release stimulation, suggesting their potential for managing diabetic complications.

It is known that aging is associated with marked effects on integrity and function of cell membrane. These effects may also be exacerbated by exogenous chemicals, e.g. sulfite. Thus, the aim of this paper is to examine the influence of sulfite on hemorheological and related hematological parameters in rats of various ages. In this study, male Wistar rats at the age of 3 and 18 months were used and the following parameters were evaluated: Mean Cell Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), Red blood Cell (RBC) deformability and aggregation. The results show that aging is associated with a decrease in RBC deformability and MCHC, an increase in MCV. Sulfite administration significantly increased RBC deformability in both young and aged rats. Although MCHC was decreased in young rats, it was increased in aged rats in response to sulfite exposure. Additionally, sulfite induced a decrement in MCV of aged rats. Neither aging nor sulfite treatment caused significant alterations in RBC aggregation parameters in all experimental groups. In conclusion, these findings suggest that RBC deformability impairs with age and sulfite has ameliorating effects on RBC deformability in both young and aged rats.

Methanolic stem-bark extracts of Adansonia digitata modulates haematological and antioxidant parameters in streptozotocin-induced diabetic rats

Urinary 3-phenoxybenzoic acid (3-PBA) levels and changes in hematological parameters in Korean adult population: A Korean National Environmental Health Survey (KoNEHS) 2012-2014 analysis.

BackgroundGastric cancer (GC) is one of the leading causes of cancer-related death worldwide. This study was designed to investigate the prognostic values of red blood cell (RBC)-associated indicators, including RBC, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW) in resectable GC patients.MethodsIn this retrospective study, a total of 104 pathologically confirmed GC patients were recruited. These cases were divided into two groups according to the median values of pretreatment RBC, HGB, HCT, MCV, MCH, MCHC, or RDW. To evaluate the changes in RBC-associated indicators values after treatment, we introduced the concept of post-/pre-treatment ratios (≤1 suggested RBC, HGB, HCT, MCV, MCH, MCHC, or RDW values were not increased after therapy, while >1 represented those in increased levels).ResultsThe lower pretreatment MCHC levels were correlated with worse overall survival (OS), while pretreatment levels of RBC, HGB, HCT, MCV, MCH, or RDW were not. The whole course of treatment (surgery plus adjuvant chemotherapy) significantly decreased the values of MCHC, and increased the values of MCV and RDW, whereas it had no obvious effects on the values of RBC, HGB, HCT, or MCH. Patients with post-/pre-treatment MCV ratio >1 had an increased survival ratio. Meanwhile, post-/pre-treatment RBC, HGB, HCT, MCH, MCHC, or RDW ratios were not correlated with outcomes. Multivariate Cox regression analysis revealed that the American Joint Committee on Cancer (AJCC) stage (III), and lower pretreatment MCHC levels were independent risk factors affecting OS. The receiver operating characteristic (ROC) curve analysis showed that an MCHC value of 341.98 g/L was the optimal cutoff value for prognosis, with a sensitivity of 58.3% and a specificity of 75.0%.ConclusionsPretreatment MCHC levels could become a potential prognostic factor for resectable GC.

Beta-thalassemia is a genetic blood disease that impacts the production of hemoglobin, resulting in observable alterations in the nature of blood cells. This paper examines complete blood count (CBC) measures in children with beta-thalassemia and compares them to those of healthy children to have a better understanding of the hematological alterations. The participants were selected to conduct the study from March to December 2024 in the Central Teaching Hospital of Pediatrics, Baghdad, and included 70 children with beta-thalassemia and 30 healthy control participants. CBC tests were done using the Shemzo automated analyzer, and the results were evaluated through p-values. Children with beta-thalassemia showed higher levels of red blood cells, white blood cells, platelets and red blood cell distribution width (RDW-CV) than controls (P = 0.002, P < 0.001, P = 0.001, and P < 0.001, respectively). However, hematocrit (HCT) and hemoglobin (Hb) levels were markedly reduced, along with significant changes in other CBC components including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils, (P < 0.001, P = 0.001). Closer monitoring of certain CBC values may help improve diagnosis and clinical management for affected children.

In this study for the first time, we investigated the correlation between sex-specific differences in adenosine triphosphate (ATP) levels in red blood cells (RBCs) and their mechanical, biochemical, and morphological alterations during the progression of atherosclerosis in ApoE/LDLR double-deficient (ApoE/LDLR−/−) mice. Our results indicate that both sex and age affect alterations in RBCs of both ApoE/LDLR−/− and C57BL/6J mice. When compared with male RBCs, female RBCs were characterized by lower basal ATP and mean corpuscular hemoglobin concentration (MCHC), higher hemoglobin concentration (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), deformability, and phosphatidylserine (PS) exposure levels, regardless of age in both, ApoE/LDLR−/− and C57BL/6J mice. ApoE/LDLR−/− mice compared with age-matched controls showed lower basal ATP levels regardless of age and sex. Intracellular ATP level of RBCs was decreased solely in senescent female C57BL/6J mice, while it was elevated in males. Basal extracellular ATP levels were 400 times lower than corresponding intracellular level. In conclusion, basal ATP levels, RBC morphology, deformability, PS exposure levels alterations are sex-dependent in mice. Changes in basal ATP levels were correlated with PS exposure and trends of changes in MCV. Trends of changes of the most RBC parameters were similar in both sexes of ApoE/LDLR−/− mice compared with age-matched controls; however, their kinetics and levels vary greatly between different stages of disease progression.

Higher amounts of cobalt chloride (CoCl2) released by industries are regarded as environmental pollutants. The goal of the current investigation was to assess the acute toxicity of CoCl2 from its effects on erythrocyte morphology and hemato-biochemical indicators in stinging catfish, Heteropneustes fossilis. The fish were subjected to CoCl2 at five different concentrations of 0, 50, 100, 200, and 300 mg L−l, which were referred to as control, CC50, CC100, CC200, and CC300, respectively. Red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), platelet counts, white blood cell (WBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), lymphocytes, granulocytes, serum protein, and blood glucose level were among the hemato-biochemical parameters of stinging catfish that were measured following a 96 h exposure period. Additionally, erythrocytic nuclear abnormalities (ENA) and erythrocytic cellular abnormalities (ECA) were evaluated in the experimental fish. As the quantity of CoCl2 increased, there were notable reductions in RBC, Hb, Hct, WBC, platelet counts, MCH, MCV, MCHC, lymphocytes, granulocytes, serum protein, and blood glucose levels compared to the control. When the CoCl2 concentration increased, the frequencies of ECA and ENA also increased significantly (P < 0.05). This work demonstrated the significant toxicity of high CoCl2 concentrations caused alterations in hemato-biochemical indices and deformities in the erythrocytes of stinging catfish. Thus, it is imperative to take all necessary corrective action to guarantee that the amount of CoCl2 in the aquatic environment stays below permissible limits.

BackgroundEffective treatment and management of sickle cell disease (SCD) has been a challenge in Africa over the years. Hematological parameters are very useful profiles in the effective management of the disease. However, there is scarcity of studies on the hematological parameters of SCD in Ghana. This study aimed at determining hematological parameters among SCD patients with vaso-occlusion, those in the steady state as well as healthy controls at a teaching hospital in Ghana.MethodologyThis was a cross-sectional study involving a total of 628 subjects, including 148 HbAA controls, 208 HbSS patients in steady state, 82 HbSC patients in steady state, 156 HbSS patients in vaso-occlusive crises (VOC), and 34 HbSC patients in VOC. Venous blood sample was collected from all study participants. A full blood count was done within 2 hours of collection, and hemoglobin (Hb) concentration, packed cell volume, red blood cell (RBC) concentration, mean corpuscular Hb, mean cell volume, mean corpuscular Hb concentration, and white blood cells (WBC) and platelet (PLT) counts were recorded.ResultsWBC and PLT counts were significantly higher in both female and male patients with SCD, compared with their healthy counterparts (P<0.05). The level of WBC was, however, significantly higher in patients with HbSS VOC among the SCD patients (P<0.001). Levels of Hb, RBC, and hematocrit were significantly higher in the controls (P<0.001). There was no significant difference in mean cell Hb among male patients with SCD (P=0.274) and female patients with SCD (P=0.5410).ConclusionThe SCD patients had lower Hb and RBC than the controls; however, higher PLT and WBC are noted in various status of SCD, possibly reflecting spleen effect in these patients. Further studies are needed to confirm these findings.

Background: Cadmium is known as a unique heavy metal compared to others, due to its long half-life, low discharge from the body, toxicity at low concentrations and accumulation in tissues. Methods: The effects of chronic and acute Cadmium (Cd) exposure were investigated on the morphology and histopathology of 24 field rats (Millardia meltada). The rats were divided into two groups of 12 each, then sub-divided into: one control and two treatment sub-groups with Cd in the feed or water. The treatment subgroups received either 15mg/kg (low) or 30mg/kg (high) Cd concentration in the feed. Results: Hemorrhagic spots and fibrosis were observed in the liver of Cd treated rats compared to the controls. Also, necrosis, dilation, and calcinosis occurred in the renal tubules of the treatment groups compared to the controls. The levels of hemoglobin, red and white blood cells, hematocrit, and mean corpuscular hemoglobin were reduced, while mean corpuscular volume and hemoglobin concentrations were increased. Conclusion: This study reports the morphological, pathological and hematological abnormalities in the blood, liver and kidneys of rats due to Cd toxicity, which may be considered as the biomarkers of cadmium toxicity in other experimental mammals.

Introduction: β-thalassemia major is a common inherited hemoglobin disorder worldwide, characterized by shortened red cell survival, defective hemoglobin synthesis, resulting in hemolytic anemia, ineffective erythropoiesis, severe anaemia, hypoxia, and hepatosplenomegaly. This study aimed to evaluate the occurrence of the JAK2 V617F mutation and JAK2 polymorphism in β-thalassemia patients compared to non-β-thalassemia controls. Additionally, the relationship between JAK2 mutations/polymorphisms and specific clinical and hematological parameters was investigated. Methods: This was a case-control study involving 71 participants, comprising 51 individuals with β-thalassemia major (patient group) and 20 healthy individuals matched for age and gender (control group). Hematological parameters were measured using an automated analyzer. Venous blood samples were collected with EDTA anticoagulant and stored at 4 °C for subsequent detection of JAK2 V617F mutation using DNA sequencing methods.Results: Analysis of β-thalassemia patients receiving regular blood transfusions revealed significantly lower levels of red blood cells (RBCs), packed cell volume (PCV), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and higher levels of white blood cells (WBC) and ferritin compared to the control group. However, the JAK2 V617F mutation was not detected in any patients or controls. The most common genotype observed in β-thalassemia patients was TC (52.94%), followed by the TT genotype, but this did not show significant associations with clinical and hematological parameters. However, there were significant differences in the frequencies of genotypes of the rs12343867 polymorphism between patients and controls.Conclusion: The study did not find evidence supporting the role of JAK2 V617F mutation in the development or clinical course of β-thalassemia. Furthermore, the mutation was not detected in the normal subjects either. The frequency of JAK2 gene polymorphism did not significantly differ between thalassemia patients and normal subjects, and different genotypes of the gene polymorphism did not show associations with demographic, clinical, or hematological parameters.

Objective To study the effects of fluorine and aluminum on index of hematologic tests of rats. Methods According to body mass,56 Wistar rats of 130-200 g were randomly divided into control,low-fluorine (F),middle-F,high-F,low-F + aluminum(Al),middle-F + Al,high-F + Al group,8 rats in each group were given a series of doses of fluoride and aluminum,which were (0 + 0),(100 + 0),(200 + 0),(300 + 0),(100 + 10),(200 + 10),(300 + 10)mg/L After 90-day intragastrie administration,blood samples were collected on eyes of rats to undergo blood routine test,including red blood cell (RBC),lymphocyte (LYM),platelet (PLT),hemoglobin (HGB),white blood cell (WBC),hematocrit (HCT),mean corpuscular hemoglobin (MCH),mean corpuscular-hemoglobin concentration(MCHC),mean corpuscular volume(MCV),and at the same time some blood biochemistry indicators related to functio ns of liver and kidney were determined such as aspartic acid aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),Crea(Cr) and Urea. Organ coefficient of liver and kidney were calculated. Results The difference of RBC,HCT,MCV among all groups of rats was statistically significant(F = 3.202,3.316,2.915,P < 0.05). The RBC,HCT of the low-F group[(7.59± 2.40)×10~(12)/L,0.51±0.11],the middle-F group[(8.60±1.16)×10~(12)/L,0.55±0.05],the high-F group[(9.23± 0.60)×10~(12)/L,0.54±0.03],the low-F + Al group[(9.25±0.79)×10~(12)/L,0.53±0.04],the middle-F + Al group[(7.98±2.14)×10~(12)/L,0.49±0.08]and the high-F + Al group[(7.61±3.17)×10~(12)/L,0.49±0.16]were significantly higher than that in the control group[(4.46±3.10)×10~(12)/L,0.31±0.16,P< 0.05 or < 0.01)]. The MCV of the middle-F group[(64.06±6.51)fl],high-F group[(58.67±1.13)fl],low-F + Al group[(57.78± 1.57)fl]and the middle-F + Al group[(63.04±10.64)fl]were significantly higher than the control group[(78.54± 15.57)fl,P < 0.05 or < 0.01]. The difference of AST and Urea among all the groups of mrs serum was statistically significant(F= 2.847,5.549,P < 0.05 or < 0.01). The serum AST of low-F group[(399.00±54.99)U/L],the middle-Fgroup[(465.60±76.99)U/L],the high-F group[(465.80±75.41)U/L],the low-F + Al group[(346.00±69.26) U/L],the middle-F + Al group[(437.40±68.31)U/L]and the high-F + Al group[(403.00±30.61)U/L]were all significantly higher than that in the control group[(336.67±94.34)U/L,P < 0.05],and the high-F group significantly higher than the high-F + Al group(P < 0.05). The serum Urea of the middle-F group[(7.70±0.52)mmol/L],the high-F group[(8.44±1.30)mmol/L],the low-F + Al group[(7.83±0.62)mmol/L],the middle-F + Al group [(7.73±0.47)mmol/L],and the high fluoride + aluminum group[(7.70±0.21)mmol/L]were all significantly higher than that in the control group[(6.55±0.50)mmol/L,P< 0.05 or < 0.01],and the low-F group was significantly lower than the low-F + Al group(P < 0.01),however the high-F group was significantly higher than that in the high-F + Al group(P< 0.05). The liver organ coefficient of the low-F group(2.94±0.36) was higher than the low-F + Al group (2.60±0.15,P < 0.05). Conclusions Fluorine and combination of aluminum and fluorine have toxicity on rats to a certain extent,including the proliferation of crythrocytes of rat,while the cell size gets smaller and the cell quality is deteriorated,meanwhile functions of liver and kidney are impaired. Aluminum shows different joint action in different concentrations of fluorine. Key words: Fluorine; Aluminum; Hematologic tests

ABSTRACTThe distinctive strength of this study lies in its comprehensive analysis of hematological and biochemical blood values, as well as morphometric and morphological data from six healthy adult spotted seals Phoca largha Pallas, 1811. This analysis includes individual, seasonal, and sexual variations, based on a total of 59–103 blood samples for hematological analytes (n = 6) and 39–89 samples for biochemical analytes (n = 6). The seals were maintained in open sea enclosures from 2019 to 2024. Blood cells, which include red and white blood cells and platelets, are described along with a series of their micrographs. Maximum levels of red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) were observed in winter for both females and males. These levels decreased in spring and summer, reaching their lowest values in autumn. The differences in RBC, MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), eosinophils, neutrophils, monocytes, glucose, creatinine, chloride, potassium, iron, urea, and ALP (alkaline phosphatase) between females and males across different seasons are presented. The highest number of significant pairwise differences was observed in RBC, HGB, MCH, eosinophils, α‐amylase, ALP, and cholesterol. These differences were less pronounced in summer compared to other seasons.

Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae

Iron deficiency anemia is recognized as one of the most important contributors to the worldwide burden of illness. It has a particularly high incidence in children and females of childbearing years in both the developed and less-developed world. It is generally recognized that serum ferritin concentration is the single most useful laboratory test in the diagnosis of iron deficiency.1 However, it has significant limitations. Ferritin is an acute phase reactant and can be increased out of proportion to iron stores when inflammation is present and even without inflammation the specific ferritin concentration that represents iron deficiency is not clearly established, particularly in females.1, 2 The authors reviewed anonymized data from 28,134 Quest Diagnostics employees participating in the Quest Blueprint For Wellness (BFW) screening program to evaluate age-specific ferritin reference intervals in a population of adults aged 18–80 years without anemia or other red cell abnormalities. In addition, changes in red cell indices in relation to serum ferritin concentrations (mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); and the coefficient of variation of the red blood cell distribution width (RDW)) as well as the hemoglobin concentration, red blood cell concentration (RBC), and the hematocrit were analyzed in order to identify a more physiologic ferritin cutoff at which changes suggestive of iron deficiency may begin to appear. Individuals with values outside the Quest reference intervals for hemoglobin concentration, hematocrit, RBC, MCV, MCH, MCHC, and RDW (reference values shown in Table S2); serum total iron binding capacity (TIBC) saturation <20%; or an International Classification of Diseases-10 (ICD 10) code indicating an anemia diagnosis or a self-reported history of anemia on their BFW health questionnaire were excluded. To exclude individuals whose serum ferritin concentrations might be elevated out of proportion to iron stores by inflammation, individuals with high sensitivity C-reactive protein (hsCRP) >3 mg/L were excluded. Data from the remaining 24 812 individuals (55% female) were analyzed as presented below. Specific details of the study population including racial/ethnic and geographic demographics are shown in Table S1 and Figure S1. The statistical technique multimodal decomposition was utilized to determine the reference ranges for serum ferritin concentrations in the final study population. Results were expressed by age deciles, with the lower limit representing the 2.5% confidence interval of population distribution for the individuals studied. A detailed description of methodology is provided in Supplemental Methods. The ferritin reference interval lower limits for females 50 years of age or younger ranged between 11 and 13 ng/mL and were substantially lower than the lower limits for males in the same age ranges (39–41 ng/mL). However, for individuals over the age of 50, the lower limits of ferritin reference intervals for females increased, approaching but not equaling or exceeding the lower limit values observed for males until age greater than 70 years (increasing from 22 to 38 ng/mL). In contrast, the lower limit for males increased for ages 18 to 30 and 30 to 40 years but then declined and by the eighth decade was lower than the lower limit for females of the same age (28 ng/mL males vs. 38 ng/mL females). To evaluate whether the TIBC saturation cutoff at 20% was appropriate for excluding potentially iron deficient patients compared to a higher TIBC saturation cutoff, the lower limits of the ferritin reference interval for age deciles in males and females were evaluated at TIBC saturations ranging from greater than or equal to 20% to greater than or equal to 25%. There were no significant increases or decreases in ferritin reference interval lower limits. Full data are shown in Table S3. Correlations between serum ferritin concentration and red cell parameters were statistically significant. The relationship between serum ferritin concentration and hemoglobin concentration, RBC, and MCV is shown in Figure 1. The nonparametric method LOESS (LOcally Estimated Scatterplot Smoothing) was utilized to fit a smooth curve and an inflection point was estimated for each curve by finding the lowest ferritin concentration where the LOESS curve started to plateau or where the rate of change on the y-axis was minimal. (Correlation values and LOESS curves/inflection points for all parameters are shown as Figures S2, S3 and in Tables S4 and S5). Changes in parameters that would be consistent with the development of iron deficiency (decreases in hemoglobin, hematocrit, RBC, MCV, MCH, and MCHC, and an increase in RDW) began to appear at serum ferritin concentrations less than 100 ng/mL. The ferritin concentrations at the inflection points for these changes were between 44 and 65 ng/mL. Ferritin concentrations at the curve inflection points in males were higher than those observed for females for all parameters, with a median difference of 10 ng/mL (95% confidence interval 2–24 ng/mL). Male/female inflection point differences were smallest for hemoglobin concentration and hematocrit (3 and 2 ng/mL, respectively), with male/female inflection point differences for other parameters studied between 9 and 21 ng/mL. Full results are shown in Table S5. It has been suggested that, while the upper limits of the hemoglobin, hematocrit, and RBC concentration reference intervals may be intrinsically higher in males because of testosterone production, the reference interval lower limits for these parameters in healthy females may not be determined by intrinsic male/female differences but by a higher incidence of iron deficiency in females.3 We examined this possibility in two ways. Ferritin reference intervals for females were recalculated after excluding individuals whose hemoglobin, hematocrit, and RBC values were below the cutoff value for males. This excluded 68% of the females in the original study population. However, the ferritin reference interval lower limits were essentially identical to those of the original study population for females under age 50 years, and only slightly higher for the 50–60 years and 60–70 years deciles (26 n/mL vs. 22 ng/mL; 31 mg/mL vs. 26 ng/mL, respectively). In all age deciles, the ferritin reference interval lower limit for males was higher, although the male/female difference decreased after age 50 years. There were too few females remaining in the 70–80 years decile for analysis. Full results are shown in Table S6. To approach this same question from the perspective that differences in the hemoglobin and hematocrit reference interval lower limits for females and males could be a consequence of an increased incidence of iron deficiency (and hence lower ferritin values) in females, the hemoglobin and hematocrit distributions were calculated for individuals with serum ferritin greater than 50 ng/mL. The value of 50 ng/mL was selected because it approximates the median inflection point identified for the parameters studied. It is also consistent with reports that physiologic indicators of iron deficiency such as increased gastrointestinal absorption of iron4 or increased serum soluble transferrin receptor concentrations and decreased serum hepcidin concentrations5 begin to appear at a serum ferritin concentration of approximately 50 ng/mL. A difference in the lower limits of the hemoglobin and hematocrit distributions between males and females persists in all age deciles. The differences remain fairly consistent (1.0–1.6 g/dL hemoglobin, 2.5%–4.0% hematocrit) for all age deciles. This range of differences encompasses the differences between the male and female reference ranges used to exclude individuals from this analysis (1.5 g/dL hemoglobin, 3.5% hematocrit). Full results are shown in Table S7. If a serum ferritin concentration of 50 ng/mL were used as the cutoff for iron deficiency in both males and females, 49.7% of females and 14.3% of males in this study population would be defined as iron deficient. When examined by age deciles, 71.5% of females in the 18–30 years category and 64.6% in the 30–40 years decile would be classified as iron deficient. The frequency of iron deficiency in females then decreases with age until it reaches 25.9% in the eighth decade of life. For males, the frequency of iron deficiency by this criterion remains between 13.3% and 14.3% until the seventh and eighth decades, when it increases slightly to 17.4% and 17.9%, respectively. Full results are shown in Table S8. There is ongoing debate about the level of ferritin that defines iron deficiency and whether absence of marrow iron stores—the traditional definition of iron deficiency—is required for evidence of functional or tissue iron deficiency. A 2017 meta-analysis by Daru et al. reported that a stainable iron score of zero corresponded to a serum ferritin of 15 ng/mL or below, while reduced iron stores (stainable iron score 1+) represented a serum ferritin of approximately 70 ng/mL.6 The present report suggests that changes in hemoglobin, hematocrit, RBC concentration, and RBC indices that could indicate early iron deficiency at a cellular level (decreasing MCV, MCH, MCHC, and increasing RDW) begin to appear at serum ferritin levels reported to indicate stainable iron stores that are reduced but not yet absent. RTM: Affinergy LLC (consultant). CB, EW, LAB: Quest Diagnostic, Inc. (full-time employees). MJM: Quest Diagnostics, Inc. (consultant/medical director). Original individual deidentified participant data that support the findings of this study are available on request. Data access requests should be addressed to Dr. Lance Bare [email protected]. The data are not publicly available due to privacy or ethical restrictions. Data S1. Supporting Information. Figure S1. Selection criteria for final study population. BFW: Blueprint For Wellness. Figure S2. Correlation between serum ferritin concentrations (ng/mL) and hemoglobin, hematocrit, and other red blood cell parameters in females. (A) Hemoglobin concentration (g/dL); (B) Hematocrit (%); (C) Red blood cell concentration (RBC; 106/μL); (D) Mean corpuscular volume (MCV; fL); (E) Mean corpuscular hemoglobin (MCH; pg); (F) Mean corpuscular hemoglobin concentration (MCHC; g/dL); (G) Red blood cell distribution width coefficient of variation (RDW; %). Figure S3. Correlation between serum ferritin concentrations (ng/mL) and hemoglobin, hematocrit, and other red blood cell parameters in males. A. Hemoglobin concentration (g/dL); B. Hematocrit (%); C. Red blood cell concentration (RBC; 106/μL); D. Mean corpuscular volume (MCV; fL); E. Mean corpuscular hemoglobin (MCH; pg); F. Mean corpuscular hemoglobin concentration (MCHC; g/dL); G. Red blood cell distribution width coefficient of variation (RDW; %). Table S1. Demographic data of individuals analyzed. Table S2. Reference interval cutoffs used to define study population. Table S3. Ferritin references ranges (ng/mL) determined by MMD at TIBC saturations 20%–25%. Table S4. Correlation between serum ferritin and RBC parameters. Table S5. Ferritin concentration curve inflection points for RBC parameters. Table S6. Ferritin reference interval lower limits in females with adjusted (male reference interval) anemia definitions. Table S7. Hemoglobin and hematocrit distribution for individuals with serum ferritin >50 ng/mL. Table S8. Percentage of individuals with serum ferritin <50 ng/mL. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.