Low Mean Corpuscular Volume Research Articles

Complete Blood Count Analysis on Beef Cattle Exposed to Fescue Toxicity and Rumen-Protected Niacin Supplementation.

Simple SummaryFescue toxicity results from cattle consuming fungal (Ergot spp.) endophyte-infected tall fescue. Ergot alkaloids like ergovaline produce vasoconstriction in cattle. Our objectives were to analyze changes in complete blood count and performance due to ergot alkaloid detoxification in growing beef cattle and the effect of selecting dams tolerant or susceptible to fescue toxicity based on their tolerance index, measured through a genetic test currently available for beef producers. Furthermore, rumen-protected niacin supplementation is proposed as a potential alleviator for vasoconstriction produced by fescue toxicity. Therefore, we assessed the effects of consuming endophyte-infected tall fescue seeds in addition to rumen-protected niacin supplementation in offspring performance and hematological parameters. Signs for anemia were noticed in susceptible heifer offspring that did not receive rumen-protected niacin, whereas inflammation or infection was detected in tolerant steers that received niacin in their diet. Typical symptoms of heat stress and intoxication with ergot alkaloids were noticed in offspring. Our results suggest that susceptible heifer offspring might have a more active detox metabolism when under fescue toxicity. Findings from this study could be utilized as a new tool to help beef cattle producers to dampen the adverse effects of fescue toxicity.Offspring born to dams genetically tested for resistance to fescue toxicity were separated in groups based on their dams’ resistance level (tolerant vs. susceptible). Rumen-protected niacin (RPN) is proposed as a potential alleviator for vasoconstriction produced by fescue toxicity. Complete blood count (CBC) analysis was utilized for detection of significant responses to treatments applied. Our objectives were as follows: (a) to analyze changes in CBC due to fescue toxicity, maternal resistance level, and RPN in growing offspring; and (b) to assess the effects of maternal resistance level when consuming endophyte-infected tall fescue seeds in addition to RPN in offspring performance. Body weight, average daily gain, or health status were not improved by RPN or the genetic test to detect fescue toxicity resistance. Typical signs of alkaloids intoxication and heat stress were noticed in offspring. Particularly, rectal temperature was greater for susceptible control heifers. Results showed that susceptible control offspring presented signs of anemia denoted by low mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). High levels of white blood cells (WBC) and basophils in combination to low neutrophils to lymphocytes ratio were the signs of infection or inflammation detected in the CBC analysis, especially in tolerant niacin steers. Furthermore, offspring of control heifers had a greater percentage of reticulocytes and RDW, denoting signs of anemia.

HEMATOLOGICAL MANIFESTATIONS OF CELIAC DISEASE AMONG CHILDREN: A SINGLE CENTER STUDY FROM SOUTH PUNJAB, PAKISTAN

OBJECTIVE: To find out various hematological manifestations among children from South Punjab, having confirmed celiac disease (CD). METHODS:  This case-control study was done at The Institute of Child Health, Multan, Pakistan, from 1st February 2019 to 31st July 2019. We enrolled 139 children having CD, ranging in age from 1-12 years. An equal number of age and gender matched controls were also enrolled. Haematological parameters were compared between cases and controls. RESULTS:    Majority (n=83/139; 59.7%) of children with CD were male. Mean age was 8.78±2.4 years. The common hematological manifestations among children with CD were anemia (n=127; 91.4%), thrombocytosis (n=104; 74.8%); leucopenia (n=10; 7.2%) and coagulopathy (n=13; 9.4%). Anemia alone was present in 20 (14.4%) children, anemia plus thrombocytosis in 91 (65.5%) cases, anemia plus leucopenia in 7 (5.0%) cases and anemia along with thrombocytosis and coagulopathy in 9 (6.5%) cases. Out of 127 cases of anemia, iron deficiency anemia (IDA) was noted in 96 (75.6%) cases, vitamin B12 and folate deficiency anemia in 14 (10.1%) cases whereas double deficiency anemia was seen in 17 (13.4%) cases. According to Modified Marsh Scoring, majority (n=46; 33.1%) of children had Type 3a CD. When compared to controls, CD cases had significantly lower haemoglobin, raised platelet count, lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels (p value<0.0001). CONCLUSION: In children having CD, hematological manifestations are common. IDA is the most frequent hematological abnormality observed along with thrombocytosis in children with CD. Hematological parameters were significantly impaired among children with CD.

Anemia in Ugandan pregnant women: a cross-sectional, systematic review and meta-analysis study

BackgroundAnemia in pregnancy represents a global public health concern due to wide ranging maternal and neonatal adverse outcomes in all peripartum periods. We estimated the prevalence and factors associated with anemia in pregnancy at a national obstetrics and gynecology referral hospital in Uganda and in addition performed a systematic review and meta-analysis of the overall burden of anemia in pregnancy in Uganda.MethodsWe conducted a cross-sectional study among 263 pregnant women attending the antenatal care clinic of Kawempe National Referral Hospital, Kampala, Uganda, in September 2020. Anemia in pregnancy was defined as a hemoglobin level of < 11.0 g/dl and microcytosis as a mean corpuscular volume (MCV) of < 76 fL. We also performed a systematic review (PROSPERO Registration ID: CRD42020213001) and meta-analysis of studies indexed on MEDLINE, Embase, African Journal Online, ClinicalTrials.gov, ICTRP, and the Cochrane Library of systematic review between 1 January 2000 and 31 September 2020 reporting on the prevalence of anemia in pregnancy in Uganda.ResultsThe prevalence of anemia was 14.1% (n= 37) (95%CI 10.4–18.8), of whom 21 (56.8%) had microcytic anemia. All cases of anemia occurred in the second or third trimester of pregnancy and none were severe. However, women with anemia had significantly lower MCV (75.1 vs. 80.2 fL, p<0.0001) and anthropometric measurements, such as weight (63.3 vs. 68.9kg; p=0.008), body mass index (25.2 vs. 27.3, p=0.013), hip (98.5 vs. 103.8 cm, p=0.002), and waist (91.1 vs. 95.1 cm, p=0.027) circumferences and mean systolic blood pressure (BP) (118 vs 125 mmHg, p=0.014). Additionally, most had BP within the normal range (59.5% vs. 34.1%, p=0.023). The comparison meta-analysis of pooled data from 17 published studies of anemia in pregnancy in Uganda, which had a total of 14,410 pregnant mothers, revealed a prevalence of 30% (95% CI 23–37).ConclusionsDespite our study having a lower prevalence compared to other studies in Uganda, these findings further confirm that anemia in pregnancy is still of public health significance and is likely to have nutritional causes, requiring targeted interventions. A larger study would be necessary to demonstrate potential use of basic clinical parameters such as weight or blood pressure as screening predictors for anemia in pregnancy.

Demir eksikliğine bağlı trombositoz olgusu

Iron deficiency is a common nutritional disorder worldwide and in our country, rarely associated with extreme thrombocytosis. It can also change in laboratory values such as low hemoglobin, low mean corpuscular volume (MCV). We describe here a case of extreme thrombocytosis in a healthy 4.5 year-old boy. He had reactive thrombocytosis due to iron defiency anemia. We ruled out other causes of anemia such as hemolysis, infection, absorption problems. We did not screen for malignancy due to rapid response to iron treatment. With this case report, we wanted to focus on the relationship between iron deficiency anemia and thrombocytosis.

Standardized microfluidic assessment of red blood cell-mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease.

We present a standardized in vitro microfluidic assay and Occlusion Index (OI) for the assessment of red blood cell (RBC)-mediated microcapillary occlusion and its clinical associations in sickle cell disease (SCD). Red blood cell mediated microcapillary occlusion represented by OI and its clinical associations were assessed for seven subjects with hemoglobin-SC disease (HbSC), 18 subjects with homozygous SCD (HbSS), and five control individuals (HbAA). We identified two sub-populations with HbSS based on the OI distribution. HbSS subjects with relatively higher OIs had significantly lower hemoglobin levels, lower fetal hemoglobin (HbF) levels, and lower mean corpuscular volume (MCV), but significantly higher serum lactate dehydrogenase levels and absolute reticulocyte counts, compared to subjects with HbSS and lower OIs. HbSS subjects who had relatively higher OIs were more likely to have had a concomitant diagnosis of intrapulmonary shunting (IPS). Further, lower OI associated with hydroxyurea (HU) responsiveness in subjects with HbSS, as evidenced by significantly elevated HbF levels and MCV. We demonstrated that RBC-mediated microcapillary occlusion and OI associated with subject clinical phenotype and HU responsiveness in SCD. The presented standardized microfluidic assay may be useful for evaluating clinical phenotype and assessing therapeutic outcomes in SCD, including emerging targeted and curative treatments that aim to improve RBC deformability and microcirculatory health.

Estimation of impedance platelet count and mean platelet volume in cases of severe microcytosis – A prospective study

Introduction: Microcytosis is a condition in which red blood cells are unusually small as measured by their mean corpuscular volume.1 The most common cause of microcytosis is iron deficiency anemia.2 In severe microcytosis, both thrombocytosis and thrombocytopenia may be seen although thrombocytosis is more frequently seen. Aim and Objectives: To study the values of platelet count and mean platelet volume in cases of severe microcytosis. Materials and Methods: A 1 year prospective study (1st January 2017 to 31st December 2017) of 200 patients was carried out in the Post Graduate Department of Pathology, Acharya Shri Chander College of Medical Sciences (ASCOMS) and Hospital, Sidhra after obtaining due clearance from Institutional Ethical Committee. Platelet count and mean platelet volume (MPV) of 200 patients with low mean corpuscular volume (MCV) was done. Results: A total of 200 patients with severe microcytosis (MCV

PSIV-27 Peripheral complete blood cell count results in pigs are impacted by gender, sow parity, and farrowing season

Abstract Complete blood cell counts have been used as a diagnostic tool across many animal species including swine. To investigate the factors that cause variation in complete blood cell count results, a total of 2,284 whole blood samples were collected from 2012 to 2019 in preweaning piglets (n = 518), nursery pigs (n = 1,704), and grower pigs (n = 60). Whole blood was collected into K2EDTA blood collection tubes and assayed using an automatic hematologic analyzer within 6 hours of collection. Data were analyzed by Mixed procedure of SAS with gender, parity group, and farrowing season as fixed effects. Body weight and age of pigs served as covariances. Farrowing season was grouped into summer (born during May to October) or winter (or November to April). Pigs that were born from first, second, and third parity, and four and above parity sows were assorted into parity group 1, 2 to 3, and 4+, respectively. Barrows had a greater concentration of total white blood cells (P &amp;lt; 0.01), lymphocytes (P &amp;lt; 0.01), and neutrophils (P &amp;lt; 0.01) compared to gilts. Barrows had lower mean corpuscular volume (P = 0.03), mean corpuscular hemoglobin (P &amp;lt; 0.01), and mean corpuscular hemoglobin concentration (P = 0.02) compared to gilts. Pigs that were farrowed in the winter season had a greater concentration of white blood cells (P = 0.01), neutrophils (P = 0.01), and the percentage of neutrophils (P = 0.03), but were lower in the percentage of lymphocytes (P = 0.03) compared to pigs farrowed during summer. Pigs born to parity four and above sows obtained a greater lymphocyte count (P = 0.01), percentage of neutrophils (P = 0.02), and percentage of lymphocytes (P = 0.01). We concluded that peripheral complete blood cells count results were affected by gender, farrowing season, and sow parity.

Demographic, Clinical, and Biochemical Predictors of Pica in a Large Cohort of Blood Donors

Background: Pica is characterized as repeatedly eating or chewing of a non-nutritious substance including, but not limited to ice, clay and dirt, starch, raw pasta, chalk, coal, paint, or paper. Life-threatening conditions, such as gastrointestinal infections and lead poisoning, may occur depending on the substance consumed. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition defines pica as an eating disorder, but with its strong link to iron deficiency, pica is also characterized as a hematological condition. Blood donation is associated with substantial iron loss. Blood donors often become iron deficient and are susceptible to pica, as well as restless legs syndrome (RLS), an often concurrent condition characterized by an irresistible urge to move legs due to uncomfortable sensations such as tingling, crawling, burn, and pain. The National Heart, Lung, and Blood Institute sponsored REDS-III program prospectively enrolled 13,403 racially diverse blood donors in its RBC Omics study to investigate demographic, clinical, hematological, and biochemical factors associated with pica. Methods: Demographic data, survey questions of pica behaviors and RLS, complete blood count (CBC), and ferritin were collected and analyzed using univariable and multivariable logistic regression analysis. Exclusion criteria were ferritin &amp;gt;800 ng/mL, body mass index (BMI) &amp;lt;17.5, and those with 9 or more donations in the 2 years prior to enrollment who were purposely oversampled for in RBC Omics. Pica was rigorously defined by questionnaire responses: 1) "Yes" to eating ice and, 2) Consumes "8 oz - 24 oz" or "more than 24 oz" of ice and, 3) At frequency of "once a day" or "several times a day". Alternatively, "yes" to eating non-ice substances regardless of amount and frequency was also characterized as pica. Results: The analysis included 11,418 donors with 7,141 Caucasians, 1,581 African Americans, 1,601 Asians, and 1,170 Hispanics. Pica was present in 1.4% (158 out of 11,418) of the study subjects. Asians were less likely to have pica than Caucasians (odds ratio [OR], 0.50 p=0.030), African Americans (OR, 0.41; p=0.014), or Hispanics (OR, 0.33; p=0.002). Females (n=6,044) were more likely to have pica than males (n=5,449; OR, 1.43; p=0.029). Donors ≤30 years were more likely to have pica than donors &amp;gt;30 years (p&amp;lt;0.001). Donors with BMI &amp;gt;30 were more likely to have pica than donors with BMI 17.5 - 25 (p=0.036) and BMI 25-30 (p&amp;lt;0.001). Ferritin was negatively associated with pica (p&amp;lt;0.001). For donors with ferritin &amp;lt;12 ng/mL 2.4% (52/2155), 12-50 ng/mL1.3% (67/5118), and &amp;gt;50 ng/mL 0.9% (39/4145) had pica. CBC values associated with low iron stores were also associated with pica: low hemoglobin (p=0.002), low hematocrit (p=0.014), low mean corpuscular volume (MCV) (p&amp;lt;0.001), and high red blood cell distribution width (RDW) (p&amp;lt;0.001). In multivariable analyses, RLS emerged as the most powerful predictor of pica in our forward stepwise logistic regression model (OR, 4.38; 95% confidence interval, 2.14 - 8.17), p&amp;lt;0.001). Other significant demographic predictors of pica included hormone supplement use (p=0.006) and nulligravida females (p=0.009). Conclusions: Iron deficiency was confirmed as a strong predictor of pica. Consistently, demographic (female), clinical (RLS) and hematological (hemoglobin, MCV, RDW) parameters associated with iron deficiency also were associated with increased risk for pica. However, pica symptoms were also reported by donors with ferritin &amp;gt;50 ng/mL suggesting that non-iron related factors influence pica presentation as well. Pica has a significant prevalence in the blood donor population, and healthcare providers should consider non-iron related factors when diagnosing pica. Disclosures Mast: Novo Nordisk: Honoraria, Research Funding.

Low rather than high mean corpuscular volume is associated with mortality in Japanese patients under hemodialysis

Recent studies have reported that high mean corpuscular volume (MCV) might be associated with mortality in patients with advanced chronic kidney disease (CKD). However, the question of whether a high MCV confers a risk for mortality in Japanese patients remains unclear. We conducted a longitudinal analysis of a cohort of 8571 patients using data derived from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 1 to 5. Associations of all-cause mortality, vascular events, and hospitalization due to infection with baseline MCV were examined via Cox proportional hazard models. Non-linear relationships between MCV and these outcomes were examined using restricted cubic spline analyses. Associations between time-varying MCV and these outcomes were also examined as sensitivity analyses. Cox proportional hazard models showed a significant association of low MCV (< 90 fL), but not for high MCV (102 < fL), with a higher incidence of all-cause mortality and hospitalization due to infection compared with 94 ≤ MCV < 98 fL (reference). Cubic spline analysis indicated a graphically U-shaped association between baseline MCV and all-cause mortality (p for non-linearity p < 0.001). In conclusion, a low rather than high MCV might be associated with increased risk for all-cause mortality and hospitalization due to infection among Japanese patients on hemodialysis.

Serum Vitamin B12 and Folic Acid in Vitiligo Patients: A Case Control Study

Background: Vitiligo is an autoimmune disease characterized by the destruction of melanocytes by immune mechanisms. The role of vitamin B12 and folate in melanin synthesis has been well recognized. Aim of the study: To evaluate the serum levels of vitamin B12 and folate in Libyan patients with vitiligo vulgaris. Patients and Methods: Blood samples for haemoglobin (Hb) level, mean corpuscular volume (MCV), serum levels of Vitamin B12 and folate were obtained from 50 patients with vitiligo vulgaris and 50 age and sex-matched healthy controls at Dermatology Department of Eljumhoria Hospital in Benghazi, Libya. Results: 50 patients with vitiligo vulgaris, with mean of age 34±6 years, 34% had active disease. Blood Hb level was non-significantly lower in 26% vitiligo patients as compared to 16% control subjects (P=0.064). A significant difference was observed regarding the MCV level which was lower in vitiligo patients in comparison to that of control subjects (P=0.03). 38% of vitiligo patients have microcytic anemia (P=0.142). None of the patients has macrocytic anemia. Female patients were found to have significantly lower Hb and lower MCV than males (P=.000). Serum vitamin B12 and folate were lower in patients than control subjects and this difference was statistically significant (P=.05, P=0.001). There was no significant correlation between serum levels of vitamin B12 and folate with sex, age, family history, duration and activity of the disease ( P >0.05). Conclusions: Decreased levels of serum vitamin B12 and folate are significantly prevalent in vitiligo patients, and screening vitiligo patients for vitamin B12 and folate deficiency may be warranted.

Combined effect of hemoglobin and mean corpuscular volume levels on incident metabolic syndrome: A population-based cohort study

Higher hemoglobin levels are associated with incident metabolic syndrome (MetS), and higher mean corpuscular volume (MCV) is associated with adverse outcomes. The objective of this study is to evaluate the combined effect of MCV and hemoglobin levels on incident MetS. In our cross-sectional study, we analyzed the prevalence of MetS in 20,162 middle-aged Japanese subjects without anemia and with normal MCV levels, as they underwent physical checkups. We subsequently analyzed incident MetS in 11,110 subjects. In order to evaluate the combined effect on incident MetS, the subjects were divided into four study groups according to cutoff values of hemoglobin and MCV for identifying the prevalence of MetS. In the cross-sectional study, hemoglobin (adjusted odds ratio [aOR], 1.02; P<0.0001 in men and OR, 1.04; P<0.0001 in women, per 1.0g/L) and MCV (aOR, 0.93; P<0.0001 in men and OR, 0.94; P=0.0005 in women, per 1.0fL) were independently associated with the prevalence of MetS. In the longitudinal cohort study, hemoglobin (adjusted hazards ratio [aHR, 1.12; P=0.0006, per 1.0g/L) and MCV (aHR, 0.96; P<0.0001, per 1.0fL) were independently associated with incident MetS in men but not in women. Then, the lower hemoglobin/higher MCV group showed decreased HRs for incidence of MetS compared with other groups of men but not of women. Among the subjects without anemia and with normal MCV levels, higher hemoglobin or lower MCV levels were associated with higher prevalence of MetS in men and women. In addition, lower hemoglobin with higher MCV showed a decreased risk of MetS in men. We suggested that the assessment of hemoglobin and MCV levels could be used as practical screening tool for MetS.

High Performance Liquid Chromatography (HPLC) Screening among Filipinos with Suspected Thalassemia

Introduction. Thalassemias and hemoglobinopathies are autosomal-recessive red blood cell disorders affectinghemoglobin (Hb) quantity and/or quality. Clinical manifestations vary from clinically asymptomatic to transfusion dependent individuals. These disorders are global in scope and is prevalent in Southeast Asia hence screening in the Philippines is very crucial for its prevention and control.Objective. Our retrospective study aimed to determine the frequency of thalassemias and hemoglobinopathies in patients referred to the Molecular Genetics Unit, Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila for High Performance Liquid Chromatography (HPLC) screening.Methods. Blood samples from patients (n=622) sent by hematologists from different parts of the country from October 2008 to February 2015 were analyzed. Extracted whole blood samples from the subjects were anticoagulated with ethylenediaminetetraacetic acid (EDTA) and were analyzed using BIORAD VARIANT™ HPLC Testing System and VARIANT™ Beta Thalassemia Short (BTS) Program kit for the detection of abnormalities in hemoglobin. Interpretation of results were based on the submitted mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) values, and Hb typing via HPLC of the patients.Results. Approximately twenty-nine percent (29.10%, n=181) of subjects were presumptively identified with thalassemias and hemoglobinopathies by HPLC. Beta-thalassemia trait, Hb E trait, and beta-thalassemia/Hb E disease were detected in 65 (10.45 %), 14 (2.25 %), and 3 (0.48 %) subjects, respectively. While suspected alpha-thalassemia, presumably Hb H disease, was found in 99 (15.92 %) patients. Interestingly, seventy-two percent (72.11%, n=318) of the patients with normal Hb typing via HPLC have low MCV and MCH values.Conclusion. Results of this study provide the spectrum and frequency of thalassemias and hemoglobinopathies in patients referred to our laboratory for HPLC analysis.

Mean Corpuscular Volume Predicts Adverse Outcomes Following Peripheral Angioplasty With Stenting and Is Associated With On-Treatment Platelet Reactivity.

Structural aspects of red blood cells have been associated with cardiovascular disease. No data linking mean corpuscular volume (MCV) to clinical outcomes and on-treatment platelet reactivity in patients with peripheral artery disease (PAD) are available. We investigated a composite of atherothrombotic events and target vessel restenosis or reocclusion following infrainguinal stenting for stable PAD. Residual platelet reactivity was measured by light transmission aggregometry (LTA) and the VerifyNow assays. We included 104 patients receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. In receiver-operating characteristic analysis, MCV effectively discriminated between patients with and without adverse outcomes and identified a MCV ≤90.8 fL as optimal cutoff. Adverse outcomes occurred significantly more often in patients with low MCV (log-rank P = .002). In univariable Cox regression analysis, low MCV was associated with an increased risk of future adverse outcomes (hazard ratio [HR]: 2.662 [95%CI: 1.304-5.434]; P = .007) and remained significantly associated after adjustment (HR: 2.591 [95%CI: 1.242-5.403]; P = .011). Mean corpuscular volume was inversely correlated with arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by LTA and with the VerifyNow aspirin assay. Low MCV is associated with adverse outcomes over 2 years following infrainguinal stenting. Mean corpuscular volume correlates inversely with AA- and ADP-inducible platelet reactivity during DAPT.

Prevalence and Utility of Low Mean Corpuscular Volume in Infants Admitted to the Neonatal Intensive Care Unit

To determine the prevalence of low mean corpuscular volume (MCV) in newborn infants admitted to the neonatal intensive care unit and to assess low MCV as a diagnostic test for alpha thalassemia. Retrospective analysis of all infants admitted to the neonatal intensive care unit between January 2010 and October 2018 for which a complete blood count was performed during the first 3 postnatal days. Infants with a low MCV were compared with those with a normal MCV. Infants with positive hemoglobin Bart (Hb Bart) were compared with those withnegative Hb Bart. Low MCV was also evaluated as a diagnostic test for alpha thalassemia. A total of 3851 infants (1386 preterm, 2465 term) met the inclusion criteria and 853 (22.2%) had a low MCV. A low MCV was more common in term (25%) compared with preterm infants (17.1%, P<.001). Hb Bart positive newborn screening was identified in 133 infants (3.5%). Hb Bart was positive in 11.1% of infants with low MCV compared with 1.3% with normal MCV (P<.001). The sensitivity, specificity, positive predictive value, and negativepredictive value of low MCV for the diagnosis of alpha thalassemia were 71.4%, 79.6%, 11.3%, and 98.7%, respectively. As Hb Bart positive newborn screens were seen in only 11.1% of infants with microcytosis, further diagnostic investigation may be warranted in individual infants. Further research to correlate microcytosis with iron status in infants and mothers is needed as well as studies using DNA analysis for the evaluation of alpha thalassemia variants.

Burden and Risk Factors of Chronic Kidney Disease in Children with Sickle Cell Anaemia Aged 5 – 16 Years at the University Teaching Hospital, Lusaka - Zambia

Background: Improved medical care has led to the improved life expectancy of sickle cell anaemia (SCA) patients hence complications associated with SCA such as chronic kidney disease (CKD) are being seen more frequently. Globally, nephropathy of varying severity occurs in 5 to 18 % of the SCA population across all age groups with a third of the adults proceeding to develop CKD while over 30 % of paediatric SCA patients have CKD in Africa. The mortality rate in SCA patients CKD is high. This study sought to determine the prevalence and risk factors of CKD in SCA, information that was not available in Zambia prior to this study. This information will guide in targeting and timing of screening for CKD in SCA in children in our population. Objectives: To determine the prevalence of haematuria, proteinuria, abnormal estimated glomerular filtration rate (eGFR), CKD, and risk factors of CKD among the steady-state SCA patients aged 5 to 16 years at the University Teaching Hospital (UTH), Lusaka. Methodology: This was a prospective cross-sectional study of 197 children aged 5 to 16 years with SCA at the UTH - Lusaka conducted from August 2014 to July 2015. Demographic and clinical data were collected using a structured questionnaire. Urine and blood samples were used to determine the urine albumin creatinine ratio (ACR) and full blood count /blood biochemistry respectively. CKD was defined and determined using the Kidney Disease Outcome Quality Initiative 2012 guidelines employing urine ACR, dipstick urinalysis and eGFR. In this study, spot urine ACR and dipstick urinalysis were done and repeated three months later if initial tests were abnormal. Data was analysed using SPSS version 21. Chi-square and t-test were used to compare proportions between groups. Relation between study variables and CKD were examined using logistic regression. Results: The mean age of the participants was 9.6 years (SD ±3.6). Male to female ratio was 1:1. The median age at diagnosis of SCA was 22 months (IQR = 44). The prevalence of haematuria, proteinuria and CKD among the study participants was 14.2%, 36% and 36 % respectively. Low haemoglobin and elevated mean corpuscular volume (MCV) were associated with CKD-AOR 0.62, 95% CI; 0.46-0.84 and 1.04, 95% CI; 1.01 – 1.08 respectively. Recurrent admissions (due to VOCs, severe anaemia and febrile illness) were also risk factors associated with CKD- AOR 0.52, 95% CI; 0.27-0.98. CKD was not associated with age at enrolment, sex, age at diagnosis of SCA, recurrent Vaso-occlusive crisis (VOCs) or abnormal liver function tests. Conclusion: The prevalence of CKD among the SCA patients at UTH- Lusaka is high (36%) with lower Haemoglobin, elevated MCV and recurrent admissions being risk factors for developing CKD. SCA patients should be screened for CKD routinely at least once a year. Interventions such as the early introduction of hydroxyurea, proactive blood transfusions and ACE inhibitors can reduce the risk of CKD and its progression to end-stage renal disease.

Hb Westmead (HBA2: c.369C>G): Hematological Characteristics in Heterozygotes with and without α0-Thalassemia

Hb Westmead (α122(H5)His>Gln) (HBA2: c.369C>G) is a common α-globin variant causing α-thalassemia (α-thal) in Mainland China. In this study, we report the hematological characteristics in Hb Westmead carriers in a Chinese population. There were 546 individuals carrying Hb Westmead based on their molecular diagnosis: 514 Hb Westmead heterozygotes and 32 compound heterozygotes for Hb Westmead and α0-thal. Compared to common deletional α+-thal, Hb Westmead was associated with higher mean corpuscular hemoglobin (Hb) (MCH) values. Compound heterozygotes for Hb Westmead and α0-thal showed significantly higher Hb, mean corpuscular volume (MCV) and MCH values than subjects with deletional Hb H disease. When compared to α0-thal carriers, compound heterozygotes for Hb Westmead and α0-thal showed similar Hb values, but significantly lower MCV and MCH values. Our results indicate that Hb Westmead is a silent nondeletional α+-thal, with a deficiency of α-globin chain milder than deletional α+-thal, and compound heterozygotes for Hb Westmead/α0-thal have a phenotype similar to simple α0-thal.

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb–thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width.Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.

Predictive values of routine blood test results for iron deficiency in children

Objective: To explore the predictive values of routine blood test results for iron deficiency (ID) screening in children. Methods: Routine blood test results and serum ferritin (SF) levels from 1 443 healthy children (862 boys, 581 girls) aged 6 months to 18 years, who were seen for well-child visits between June 2017 and May 2019 in Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. ID was defined as SF<20 μg/L, iron deficiency anemia (IDA) as ID with anemia (hemoglobin(Hb)<110 g/L at 6 months-5 years of age, Hb<120 g/L at 6-18 years of age), non-anemia ID as ID without anemia, non-ID anemia as SF≥20 μg/L with anemia, and healthy control subjects as those with SF≥20 μg/L but without anemia. The blood test results including Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), and the percentage of low hemoglobin density (LHD) of healthy control, non-anemia ID, non-ID anemia, and IDA groups were compared by analysis of variance (ANOVA) or non-parametric test, quantitative data were described as x±s or M(interquartile range), and receiver operating characteristic curve (ROC) analysis was applied to assess predictive values of routine blood test results and LHD for detecting IDA and ID. Results: Among 1 443 children with median age of 2.1(3.3) years, 1 061 children were in healthy control group, 292 in non-anemia ID group, 43 in non-ID anemia group and 47 in IDA group. The prevalence of ID was much higher than that of anemia (23.5% (339/1 443) vs. 6.2% (90/1 443) , χ(2)=169.76, P<0.01). Compared with control group, non-anemia ID group showed higher LHD (0.088 (0.093) vs.0.073 (0.068), P<0.01) and RDW (0.131±0.013 vs. 0.126±0.008, P<0.01), lower MCV ((80±4) vs. (83±4) fl, P<0.01) and MCHC values ((326±9) vs. (329±8) g/L, P<0.01). IDA group showed higher LHD (0.322(0.544)) and RDW (0.151±0.018), lower MCV ((73±6) fl) and MCHC values((309±14) g/L) than non-anemia ID group (all P<0.01). The area under curve (AUC) values of MCHC, LHD, RDW and MCV for detecting ID were 0.63 (95%CI: 0.60-0.67), 0.63 (95%CI:0.60-0.67), 0.67 (95%CI: 0.63-0.70) and 0.73 (95%CI: 0.69-0.76) respectively. With cutoff limits (MCV<80.2 fl, RDW>0.131 or MCHC<322 g/L), MCV, RDW and MCHC showed higher sensitivity for screening ID than hemoglobin (0.540, 0.469 and 0.336 vs. 0.139, χ(2)=121.70, 87.47, 35.56, all P<0.01). Conclusion: MCV, RDW and MCHC can be used to screen ID in primary health care settings.

Microcytic anemia in children: parallel screening for iron deficiency and thalassemia provides a useful opportunity for thalassemia prevention in low- and middle-income countries

Microcytic anemia in children is commonly attributed to iron deficiency without attempting to find the cause. Inadequate investigations to exclude hemoglobinopathies lead to missed opportunities for identification of thalassemia carriers. Here we aim to describe the relative contribution of iron deficiency and thalassemia to microcytic anemia in children. This hospital-based prospective study was conducted at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All newly diagnosed patients with microcytic anemia were recruited and data were collected using an interviewer-administered questionnaire. Full blood count, blood film, serum ferritin, c-reactive protein, quantification of hemoglobin sub-types and α-globin genotype were performed using 4 ml of venous blood. A total of 104 children (Male- 60.5%) were recruited. Iron deficiency was the cause for anemia in 49% whilst 16% and 10% had α- and β-thalassemia trait respectively. Seven (6.7%) children had co-existing iron deficiency and thalassemia trait while two coinherited α- and β-thalassemia trait. Children with β-thalassemia trait had significantly higher red cell count and lower mean corpuscular volume compared to children with iron deficiency. However, none of the red cell parameters were significantly different between children with α-thalassemia trait and iron deficiency. Iron deficiency contributes only to half of children with microcytic anemia; one-fourth had thalassemia trait. Co-existence of iron deficiency and thalassemia trait or co-inheritance of α- and β-thalassemia trait were found in 9%. Parallel investigation of children with microcytic anemia to diagnose iron deficiency and thalassemia provides an opportunity to identify thalassemia carriers which is beneficial for thalassemia prevention.

Estimation of the risk of fibrosis in children with nonalcoholic fatty liver disease.

Aim of the studyAssessment of liver fibrosis as a predictive factor of liver-related mortality in children with nonalcoholic fatty liver disease (NAFLD) is crucial. This study aims to estimate the risk of fibrosis using noninvasive markers.Material and methodsThe study group of 49 children with NAFLD (age range 3-16, mean 10.51 ±3.18 years) was created. The diagnosis was based on clinical picture, abdominal ultrasound, and laboratory tests; four children underwent liver biopsy. Then homeostatic model assessment (HOMA-IR) and noninvasive hepatic fibrosis scores were calculated, and patients were divided into four groups depending on body mass index (BMI, obese vs. lean) and aminotransferases.Results71.43% of patients were obese, and 14.29% were overweight. We found that overweight children had lower mean corpuscular volume (MCV) than lean patients. In a group of patients with a high risk of fibrosis or significant fibrosis due to pediatric NAFLD fibrosis score (PNFS), higher alanine aminotransferase (ALT) to platelet ratio (APRI) values were observed. The highest values of APRI were found in a group of lean patients with elevated aminotransferases and the highest value of PNFS – among obese patients with elevated aminotransferases. A strong significant correlation between APRI and PNFS was found (r = 0.88).ConclusionsApart from aminotransferase activity, complete blood count should be assessed looking for lower MCV caused by iron deficiency. In contrast to FIB-4 (fibrosis score), PNFS and APRI proved to be more accurate in our group. PNFS seems to be appropriate to evaluate fibrosis in a noninvasive diagnostic algorithm.