Establishing Reference Intervals for Hematological, Biochemical, and Immunological Analyses Among Urban Ghanaian Adult Population

ABSTRACT

Background Reference intervals (RIs) refer to the upper and lower reference limits of laboratory test derived from healthy individuals recruited with well-defined criteria. RI serves as a comparison tool and an important determinant of whether an individual is healthy or not, which apparently remains the most extensively used decision-making tool in clinical settings. Considering the importance of RIs for the interpretation of laboratory test, the International Federation of Clinical Chemistry (IFCC) has recommended that each laboratory obtains its own reference values and estimate the corresponding RIs within defined procedures. Even though the recommendation from IFCC/Clinical laboratory standard institute (CLSI) is required, yet majority of diagnostic laboratories in Ghana are unable to implement their own RIs due to the cost and challenges involved in recruiting the reference population. For that reason, the majority of laboratories work with reference intervals that are based on guidelines developed by manufacturers of analyzers.

Thus, the continual use of such existing RIs from different manufacturer analyzers affects clinical decision making and might lead wrong interpretation of laboratory results, which is a public health concern. Aim This study aimed to establish reference intervals for hematological, biochemical and immunological analyses that would inform context-specific clinical decision-making and interpretation of laboratory results for healthcare practice in Ghana. Methods in a cross-sectional study design; healthy individuals, aged 18 – 60+ years were recruited using a simple random sampling technique. A total of 501 apparently healthy subjects; from the Tamale and Accra Metropolis which are capital cities of the Northern and Greater xxiv Accra region respectively were recruited into the study. Structured questionnaires were administered to volunteers to collect data on demographics, lifestyles, dietary pattern and their clinical information.

 The selection of eligible participants was primarily based on well-defined inclusion and exclusion criteria, which were in accordance with the IFCC/CRIDL protocol. A fasting blood sample of 24mL was drawn into two plastic evacuated tubes containing ethylene diamine tetra-acetic acid (EDTA), three serums separate tube (SST), one sodium fluoride (NaFl) tube and one lithium heparin tube for complete blood count (CBC) and clinical chemistry analysis. Whole blood samples were analyzed using Sysmex XN 1000 analyzer for haematology analytes while the clinical chemistry, immunoglobulin, hormones, and tumour marker analytes were analyzed using Beckman Coulter AU 480 analyzer, Roche Cobas e411 analyser and Centaur XP Siemens’ analyzer respectively. All laboratory investigations were carried out in accordance with the laboratory’s standard operating procedures (SOPs). Stata version 13 software (Stata Corp., College Station, Texas, United States) was used in analyzing the data. Multiple regression analysis was performed to determine the relationship between variables. Partitioning of reference values by sex and age was done by the computing standard deviation ratio (SDR) using 3-level nested ANOVA by StatFlex version 6.0 statistical software (Artech Inc., Osaka, Japan). Prior to the derivation of the RIs, the latent abnormal values exclusion (LAVE) method was conducted to exclude individuals with such latent diseases. The latent abnormal values exclusion (LAVE) method is a secondary exclusion procedure applied to refine the data. Using “Reference interval Master” software, RIs of each analyte were derived using the parametric method.