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      Routine clinical chemistry and haematological test reference intervals for healthy adults in the Bhutanese population

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          Abstract

          Laboratory medicine plays a critical role in the modern healthcare system, and it is reported to influence 60–70% of clinical decision makings. The quantitative laboratory test results are interpreted by comparing to the Reference Intervals (RIs) and therefore the use of appropriate RIs is critical. Clinical laboratories in Bhutan have been randomly using RIs from textbooks and manufacturer’s package inserts without even verifying their applicability and therefore lessening their contribution to clinical decision makings. To improve the healthcare service delivery in Bhutan, this study aims to establish routine clinical chemistry and haematological test RIs for healthy adults in the Bhutanese population. Out of 1150 (male, n = 570; female, n = 580) healthy Bhutanese adults listed for the study through a simple random sampling technique, 1002 (male, n = 405; female, n = 597) individuals were assessed and 815 (male, n = 372; female, n = 443) individuals were enrolled in the study. An adequate volume of venous blood was drawn from these participants with the use of standard phlebotomy technique for clinical chemistry and haematological analysis. The laboratory data were analysed with the use of statistical methods recommended by the International Federation of Clinical Chemistry and Laboratory Medicine and Clinical and Laboratory Standards Institute. After excluding the test results indicating underlying pathology and statistically detected outliers, a maximum of 775 (male, n = 346; female, n = 429) and 784 (male, n = 351; female, n = 433) individuals test values were eligible for clinical chemistry and haematology RIs establishment respectively. Statistically, there were no significant differences between age groups of same-sex for both test categories; however, significant differences between sex were observed for various test parameters in both test categories. Our RIs are generally comparable to other published literature. The established RIs are applicable to all the adult Bhutanese population; however, clinical laboratories should validate the transference of these RIs before using them for clinical purposes.

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          Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?

          Anemia is a global public health problem affecting both developing and developed countries at all ages. According to the World Health Organization (WHO), anemia is defined as hemoglobin (Hb) levels <12.0 g/dL in women and <13.0 g/dL in men. However, normal Hb distribution varies not only with sex but also with ethnicity and physiological status. New lower limits of normal Hb values have been proposed, according to ethnicity, gender, and age. Anemia is often multifactorial and is not an independent phenomenon. For the classification and diagnosis the hematologic parameters, the underlying pathological mechanism and patient history should be taken into account. The aging of population, especially in Western countries, causes an increase of anemia in elderly people. In this population, anemia, recently defined by levels of Hb <12 g/dL in both sexes, is mostly of mild degree (10-12 g/dL). Understanding the pathophysiology of anemia in this population is important because it contributes to morbidity and mortality. In one third of the patients, anemia is due to nutritional deficiency, including iron, folate, or vitamin B12 deficiency; moreover, anemia of chronic disease accounts for about another third of the cases. However, in one third of patients anemia cannot be explained by an underlying disease or by a specific pathological process, and for this reason it is defined "unexplained anemia". Unexplained anemia might be due to the progressive resistance of bone marrow erythroid progenitors to erythropoietin, and a chronic subclinical pro-inflammatory state.
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            The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences.

            Men and women have different mean haemoglobin levels in health in venous blood - women have mean levels approximately 12% lower than men. A similar sex-related difference in haemoglobin levels in adult animals is found in many species of mammals, birds and reptiles, indicating that it is an important physiological phenomenon. It is probably a direct effect of sex hormones, both oestrogen and androgens, on erythropoiesis. However, since there is no difference in erythropoietin levels between the sexes, this effect most likely takes place in the kidney, rather than in the bone marrow. Oestrogens dilate and androgens constrict the renal microvasculature: dilation and vasoconstriction in vessels below 300 μm in diameter respectively increase and decrease the haematocrit in blood in arterioles, capillaries and venules, altering the oxygen delivery per unit red cell mass, and providing a mechanism for varying the red cell mass without compensatory changes in erythropoiesis.
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              Establishing reference intervals for clinical laboratory test results: is there a better way?

              Reference intervals are essential for clinical laboratory test interpretation and patient care. Methods for estimating them are expensive, difficult to perform, often inaccurate, and nonreproducible. A computerized indirect Hoffmann method was studied for accuracy and reproducibility. The study used data collected retrospectively for 5 analytes without exclusions and filtering from a nationwide chain of clinical reference laboratories in the United States. The accuracy was assessed by the comparability of reference intervals as calculated by the new method with published peer-reviewed studies, and reproducibility was assessed by the comparability of 2 sets of reference intervals derived from 2 different data sets. There was no statistically significant difference between the calculated and published reference intervals or between the 2 sets of intervals that were derived from different data sets. A computerized Hoffmann method for indirect estimation of reference intervals using stored test results is proved to be accurate and reproducible.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 September 2022
                2022
                : 17
                : 9
                : e0273778
                Affiliations
                [1 ] Quality Assurance and Standardization Division, Secretariat, Ministry of Health, Thimphu, Bhutan
                [2 ] Faculty of Postgraduate Medicine, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan
                [3 ] Department of Pathology and Laboratory Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan
                [4 ] Department of Pathology and Laboratory Medicine, Eastern Regional Referral Hospital, Mongar, Bhutan
                [5 ] Department of Pathology and Laboratory Medicine, Central Regional Referral Hospital Gelephu, Gelephu, Bhutan
                [6 ] Department of Pathology and Laboratory Medicine, Bajo Hospital, Wangdue Phodrang, Bhutan
                [7 ] Department of emergency, Bajo Hospital, Wangdue Phodrang, Bhutan
                Stellenbosch University Faculty of Medicine and Health Sciences, SOUTH AFRICA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ ST, CD, PDS, N, JT, CW, SZ, KD and ST also contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-0885-8533
                https://orcid.org/0000-0002-5921-1342
                https://orcid.org/0000-0002-6212-0724
                https://orcid.org/0000-0003-1914-0831
                Article
                PONE-D-22-15438
                10.1371/journal.pone.0273778
                9436133
                36048813
                fdaf49a4-9b52-48c6-85f8-87815eb483fc
                © 2022 Dorji et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 May 2022
                : 15 August 2022
                Page count
                Figures: 0, Tables: 7, Pages: 21
                Funding
                Funded by: Quality Assurance and Standardization Division (QASD), Ministry of Health (MoH), Royal Government of Bhutan (RGoB).
                Award Recipient :
                The study was supported by the Quality Assurance and Standardization Division (QASD), Ministry of Health (MoH), Royal Government of Bhutan (RGoB). https://www.moh.gov.bt/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Biochemical Analysis
                Clinical Chemistry
                Medicine and Health Sciences
                Hematology
                Medicine and Health Sciences
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Clinical Laboratories
                People and Places
                Geographical Locations
                Asia
                Bhutan
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Platelets
                People and Places
                Population Groupings
                Age Groups
                Research and Analysis Methods
                Cell Enumeration Techniques
                Total Cell Counting
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Red Blood Cells
                Custom metadata
                Data cannot be shared publicly because the data belongs to the Ministry of Health, Royal Government of Bhutan. Data are available from the Research Ethics Board Of Health (REBH, Mistry of Health, https://www.moh.gov.bt/about/program-profiles/357-2/) via rebhscretary@ 123456gmail.com/ 02-322602/328091 ext-308 for researchers who meet the criteria for access to confidential data.

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