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

Abstract

Background: Haemoglobinopathies are inherited haemoglobin disorders that result in anaemia characterised by erythrocyte anisopoikilocytosis. Red cell distribution width (RDW) measures anisopoikiloytosis and is readily reported by haematology analysers as a complete blood count parameter. The utility of RDW as a diagnostic marker of haemoglobinopathies in Kenya remains undetermined and undocumented.

Objective: This study aimed to determine the diagnostic efficacy of RDW in discriminating haemoglobinopathy and haemoglobinopathy-free cases in Kenya.

Methods: The case-control study used randomly selected haematology analyser outputs for haemoglobinopathy-free (241, 49.4%) and haemoglobinopathy cases (247, 50.1%) aged 1 month to 66 years old tested in the Aga Khan Hospital, Kisumu, and its satellite centres in western Kenya from 01 January 2015 to 31 December 2020. Results were verified using high performance liquid chromatography. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of RDW as a biomarker for sickle cell disease (SCD) and sickle cell trait phenotypes and β-thalassaemia.

Results: The RDW showed diagnostic significance in SCD phenotypes at 21.1 ROC curve coordinate with 67.7% sensitivity, 90.0% specificity, 0.789 accuracy, 70.5% positive predictive validity, 88.8% negative predictive validity, 6.77 positive likelihood ratio, 0.36 negative likelihood ratio and 18.94 (11.4-31.4) odds ratio.

Conclusion: An RDW of 21.1% is potentially a predictor of SCD haemoglobin phenotypes and should be included in the haematology screening algorithm as a critical value, above which suspected cases qualify to be investigated for SCD.

Keywords: biomarker; haemoglobinopathies; patients; red cell distribution width; surrogate marker; western Kenya.

FIGURE 1

Red cell distribution width, ROC curve in SCD phenotypes (haemoglobin SS genotype, haemoglobin SS genotype + haemoglobin F, haemoglobin SS genotype + β-thalassaemia) in western Kenya, 01 January 2015 – 31 December 2020. (a) Red cell distribution width ROC curve in diagnosis of homozygous SCD. (b) Red cell distribution width ROC curve in diagnosis of sickle cell disease with haemoglobin F. (c) Red cell distribution width ROC curve in diagnosis of SCD with β-thalassaemia.

FIGURE 2

Red cell distribution width ROC curve in sickle cell triat phenotypes (haemoglobin AS genotype and β-thalassaemia) in western Kenya, 01 January 2015 – 31 December 2020. (a) Red cell distribution width, receiver operating characteristic curve for sickle cell trait flowing along diagonal line of the ROC curve. (b) Red cell distribution width, receiver operating characteristic curve for sickle cell trait+β-thalassaemia also flowing along the diagonal line of the ROC curve.

FIGURE 3

Red cell distribution width ROC curve in β-thalassaemia in western Kenya from 01 January 2015 – 31 December 2020.

FIGURE 4

Red cell distribution width ROC curve in haemoglobin SS phenotypes in western Kenya, 01 Janauary 2015 – 31 December 2020. This ROC curve demonstrates the efficacy of RDW at 21.1% optimal point in SCD (Haemoglobin SS) phenotypes diagnosis.