Red cell distribution width as a surrogate marker of haemoglobinopathies in western Kenya

Mutua, Benard; Sowayi, George; Okoth, Patrick

doi:10.4102/ajlm.v11i1.1644

Cited by 3 publications

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“…A readily measured hemoglobinopathy biomarker enabling affordable detection of the condition in resource-limited settings is urgently needed. Hemoglobinopathies are hereditary disorders of hemoglobin, associated with often fatal anemia [1]. They are an increasing but neglected global public health problem that needs urgent attention of the global community [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the apparent potential of this hematological index as a diagnostic marker for hemoglobinopathies, the literature reviewed reports no previous rigorous evaluation of its utility for this purpose in Kenya and indeed Africa. Owing to the reported variation in biological characteristics between human populations in different geographical locations due to the impact of physical and sociocultural environment on the expression of genes for various phenotypic characteristics, it is uncertain as to whether the findings of these studies are generalizable to Kenya [1,8,28]. Besides, even in these studies, the utility of RDW as a hemoglobinopathy diagnostic biomarker has not been rigorously and formally evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Potential of RDW in Discriminating Hemoglobinopathies among Patients reporting to Aga Khan Hospital, Kisumu

Mutua

Sowayi

Okoth

2022

Egypt J Med Hum Genet

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Background Red cell distribution width (RDW) measures the extent of variation in red blood cell (RBC) volume in terms of coefficient of variation. It reflects the degree of variation in RBC’s sizes and shapes, characteristic of iron deficiency and anemias involving RBC destruction, especially hemoglobinopathies. Its values are often available as one of the RBC indices generated as complete blood cell count (CBC) using automated hematology analyzers. Hemoglobinopathies are highly prevalent in malaria-endemic geographical settings like the Sub-Saharan African which has over 200,000 currently documented annual major hemoglobinopathies with an alarming mortality rate of 50–90% by the age of 5 years usually undiagnosed. With a vast growing majority of hemoglobinopathy carriers, this public health problem is projected to escalate by the year 2050 due to unaffordable laboratory tests for screening of newborns and populations as recommended by World Health Organization in resource-limited settings. Therefore, innovative of a cost-effective diagnostic method would improve the survival of these children. The current study aimed to evaluate the overall ability of RDW in discriminating hemoglobinopathy and hemoglobinopathy-free cases within the Lake Victoria Economic Block region of Western Kenya served partly by the Aga Khan Hospital, Kisumu. Objective To determine the significance of RDW as a tool to differentiate between individuals with hemoglobinopathies and those without. Method This was a cross-sectional retrospective comparative hospital-based study that analyzed data from the hematology laboratory database for patients examined using high-performance liquid chromatography during the years 2015–2020. The study consisted of 488 participants (49.4%, n = 241 control; 50.6% n = 247 case, p = 0.786) aged between 1 month and 66 years selected conveniently through census. The relationship between RDW of the controls and cases was analyzed using Mann–Whitney U, Kruskal–Wallis tests among population groups and Dunn’s post hoc test within groups since the data were non-normally distributed. Results The RDW cutoff value was computed at 95% confidence interval (CI), and values greater than this indicated a diagnosis of hemoglobinopathy. Conclusion RDW at 95% CI was 19.9 [14.5 + (2.7 × 2 = 19.9)] cutoff point which proved to be an excellent screening tool for sickle cell disease phenotypes in Western Kenya but would generate many false positive and false negatives for pure Hb AS. RDW is a poor screening tool for, Hb AS + HbF, Hb AS + β thal and β-thalassemia since it could not differentiate diseased from non-diseases populations. Even though RDW proved to be a poor screening tool for beta thalassemia, other complete blood count (CBC) parameters such as MCV and red cell count can be used to identify thalassemia syndromes as well as iron deficiency anemia. Though out of the scope of this work, highlighting the significance of these parameters in addition to the RDW would improve its feasibility as a screening tool for all hemoglobinopathies. Normal reference range for children ≤ 5 years needs to be developed using prospective data for precise marking of disorders associated with red cell anisocytosis, and individuals ≥ 6 years can share RDW normal reference range regardless of their gender.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Potential of RDW in Discriminating Hemoglobinopathies among Patients reporting to Aga Khan Hospital, Kisumu

Mutua

Sowayi

Okoth

2022

Egypt J Med Hum Genet

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Distribution of hemoglobinopathy phenotypes in western Kenya: a retrospective study done at Aga Khan Hospital, Kisumu

2022

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Background Hemoglobinopathies are inheritable disorders of hemoglobin and are the most common genetic defects in humans. This is a neglected public health problem whose undiagnosis remain a major threat to its prevention and control in sub-Saharan Africa countries; thus its exact magnitude on morbidity and mortality remains poorly documented. These hemoglobin disorders have been associated with Plasmodium falciparum; therefore, the current study sought to determine its distribution in a malaria-holoendemic region of Western Kenya as part of remedial intervention recommended by World Health Organization (WHO). Method This study analyzed data conveniently selected through census from 2015 to 2020 from hematology laboratory database for patients examined in Aga Khan, Hospital, Kisumu, and its satellites in Western Kenya. A total of 247 cases were selected whose sample size was calculated using Cochran’s formula. Distribution of hemoglobinopathies based on stations, gender, and age was expressed in frequencies, proportions, bar graphs, and pie charts. Results The distribution of hemoglobinopathies had varying proportions in different locations in Western Kenya with regions that were at proximity to Lake Victoria (Kisumu 41.3%, n = 102; Busia 21.5%, n = 53; Homabay 15.4%, n = 38) recording a higher overall hemoglobinopathy proportions than those that were far from the lake that include Bungoma 5.7%, n = 14; Kakamega 4.0%, n = 10; Kitale 4.0%, n = 10; Kisii 4.0%, n = 10, and Migori 4.0% n = 10. Conclusion The study represents the burden of hemoglobinopathies in a malaria-holoendemic region of Western Kenya, and even though the present study did not include ethnicity in data collection, stations from where the data was collected are predominated by different communities; therefore, there may be an ethnic correlation in the variation of hemoglobinopathies in Western Kenya. The communities juxtaposed to the lake seems to be the most affected ethnic group along the Lake Victoria economic block region; thus, it may be erroneous to assume that the entire malaria-holoendemic region of Western Kenya has high prevalence of hemoglobin disorders without factoring ethnicity and geographical location in a properly conducted population-based prevalence study in the wider Western Kenya.

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High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

et al. 2022

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Background Western Kenya, being a malaria-endemic region, has a high prevalence of hemoglobinopathies mostly sickle cell and thalassemia. The hemoglobin fractions or variants, HbA, HbA2, and HbF, serve as biomarkers for the detection of hemoglobinopathies and are commonly used in laboratory screening and diagnosis of these diseases. Diagnosis of diseases entails accurate and precise representation of a patient’s condition. This is the main aim of International Organization for Standardization (ISO) certified laboratories of offering a reliable diagnostic guide for the various diseases. For this to be realized, valid normal reference ranges are required. Such are reference values that are valid for local population of the setting where they are to be used is critical in quantitative diagnostic tests. Local normal reference ranges are necessary because research has revealed variations in the phenotypic expression of the genes for biological characteristics in humans inhabiting different geographical regions, owing to epigenetic differences imposed by physical environments, and associated sociocultural influences, even in cases of similarity in gene patterns. No local normal reference ranges for hemoglobin fractions are reported for Kenya and Africa as a whole. Laboratories therefore continue to use those found in textbooks and brochures from manufacturers of diagnostic reagents, which are derived from populations of geographical locations faraway and socioculturally different from Kenya. This could be misleading in diagnosis of hemoglobinopathies in western Kenya and indeed all of Kenya. Therefore, the present study aimed at exploring the possibility of developing local normal reference ranges for the concentrations of hemoglobin fractions, HbA, HbA2, and HbF, based on hemoglobinopathy-free, non-anemic subjects attending the Aga Khan Hospital Kisumu in western Kenya and its satellites. The hospital serves the populations inhabiting in and predominantly indigenous to western Kenya. Objectives To derive the 95% confidence intervals for hemoglobin fractions (HbA, HbA2, and HbF), evaluate the potential of these intervals as normal reference values for the local population by use of concentrations for non-anemic hemoglobinopathy-free subjects and compare the performance of the current HPLC normal ranges with those intervals we derived, based on receiver operating characteristic (ROC) curve. Materials and methods This was an analytical retrospective study using routine assay results from laboratory database for 386 non-anemic, HPLC-confirmed hemoglobinopathy-free subjects. Blood samples were obtained at the Kisumu Aga Khan Hospital and its satellite sites in western Kenya, covering January 2015 to November 9, 2021. The data for Hb fractions were nonparametric, and so confidence intervals, together with the age of subjects, were thus expressed as the median and interquartile range (IQR). Data for the gender and other characteristics of study subjects were summarized in frequencies and proportions, Kruskal-Wallis H-test was used to test the significance of differences in Hb concentrations between stations and age groups, while Mann-Whitney U-test is between males and females. The receiver operating characteristic (ROC) curve was used to evaluate the potential of the derived confidence intervals as normal reference values in comparison with the commonly used normal values for hemoglobin fractions. Results The potential normal reference intervals were computed as 95% confidence intervals (CI) for median percentage levels for the concentrations of the Hb fractions HbA, HbA2, and HbF for the hemoglobinopathy-free patients. The overall confidence intervals were derived first for the combined sample of all the hemoglobinopathy-free patients combined together irrespective station where blood specimens were obtained, age or gender, and then followed by those for separate groups, stratified based on station, age, and gender. The overall median values for the hemoglobin fractions were hemoglobin: A (HbA) 87.7, IQR = 5.7, 95% CI = 76.3–99.1; hemoglobin A2 (HbA2), 3.0, IQR = 0.6; 95% CI = 1.8–4.2; and hemoglobin F (HbF), 0.8, IQR = 0.8; 95% CI = 0.00–2.4, with the P window, 4.98, IQR = 0.4; 95% CI = 4.18–5.78. The commonly used normal reference ranges for the hemoglobin fractions were as follows: HbA 95–98%, had an accuracy of 57.5%, HbA2 of 1.5–3.5%, had an accuracy of 95.9% in grading the presumed healthy population as hemoglobinopathy-free, while HbF 0–2.0 was equal to that established by the present study. Conclusion It is important to report that the use of normal range for HbA of 95–98% published by Kratz et al. [1] in western Kenya has a potential threat of misdiagnosis of normal population and thus needs urgent review as it lacked efficacy (p = 0.795) in grading hemoglobinopathy-free subjects as normal with a poor accuracy of 57.5%, a sensitivity of 100%, specificity of 0.3%, positive predictive validity of 15.1%, negative predictive validity of 1%, and 1.03 positive likelihood ratio. However, the traditional normal range for HbA2 of 1.5–3.5% on use in western Kenya may be retained as it was effective (p < 0.0001) in grading majority of study subjects as normal with an accuracy of 95.9%, sensitivity of 98.4%, specificity of 93.3%, positive predictive validity of 99.7%, negative predictive validity of 70.0%, 14.7 positive likelihood ratio, and 0.017 negative likelihood ratio. Similarly, the existing normal range for HbF of 0–2.0 on use was almost the same as the one we derived of 0–2.4 and therefore may be retained for use in western Kenya. It is anticipated that the finding of this study will help improve the management of hemoglobinopathies in Kenya and Africa at large, by contributing to improvement in the validity of the clinical-pathologic interpretation assay results for the percentage values for the Hb fractions.

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Red cell distribution width as a surrogate marker of haemoglobinopathies in western Kenya

Cited by 3 publications

References 28 publications

Prognostic Potential of RDW in Discriminating Hemoglobinopathies among Patients reporting to Aga Khan Hospital, Kisumu

Prognostic Potential of RDW in Discriminating Hemoglobinopathies among Patients reporting to Aga Khan Hospital, Kisumu

Distribution of hemoglobinopathy phenotypes in western Kenya: a retrospective study done at Aga Khan Hospital, Kisumu

High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

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