Reference Intervals of Haematological Indices for Young Adults with Sickle Cell Anaemia in Southwestern Nigeria

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Asafa, Ibrahim Oluwaseun. Ahmed, Mary Boluwatife. Agim, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5746062/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 May, 2025 Read the published version in BMC Research Notes → Version 1 posted 10 You are reading this latest preprint version Abstract Background Reference intervals (RIs) are crucial for the interpretation of results and overall patient management. Of note, there are no established reference values for haematological parameters for patients with sickle cell anaemia (SCA) in Nigeria, making it difficult for clinicians to interpret and diagnose abnormalities appropriately. Objective This study aimed at establishing RIs of some haematological indices for individuals with SCA. Methods This descriptive cross-sectional study, included a total of six hundred and seventy-eight (337 males and 341 females) young adults with SCA aged 18–35 years. The full blood count (FBC) was done using a haematology autoanalyzer. The haematological indices were classified using 2.5th and 97.5th percentiles and delineated as low ( 97.5th percentile). All analyses were done using SPSS IBM, version 20.0 software Results Generally, the reference interval for Haematocrit is 5.2-9.2g/dl, while the WBC ranged between 5.9 to 12.1 x 10 9 /l and the platelet count is 166–465 x 10 9 /l. For the male participants, the reference interval of the haematocrit was found to be between 5.2-9.3g/dl, the WBC ranged between 6.7 to 12.1 x 10 9 /l and the platelet count was between 166 x 10 9 /l to 399 x 10 9 /l. The female subjects had a haematocrit of between 5.5g/dl to 8.8 g/dl, WBC of between 5.9 10 9 /l and 12.96 x 10 9 /l and the platelet count was between 225 x 10 9 /l and 465 x 10 9 /l. Conclusion This study has established the reference intervals for the haematological indices in individuals with SCA Sickle cell anaemia Haematological indices reference values young adults Background Sickle cell disease (SCD) is considered a global burden, it is predicted to affect approximately 14 million newborns by the year 2050 ( 1 ). Currently, Nigeria has the highest burden of the disease. ( 2 ) SCD refers to a chronic inherited disorder caused by the inheritance of a mutated haemoglobin S gene and another abnormal haemoglobin. The homozygous inheritance of the Hb S gene is referred to as sickle cell anaemia (SCA). The haemoglobin S results from a point mutation which leads to the substitution of glutamic acid for valine at position 6 in the β-globin chain. The resultant Hb S with clinical features arising from the polymerization of this abnormal haemoglobin forming deformed red blood cells with characteristic sickle-shaped. ( 3 , 4 ) Although this molecular defect has been known for several decades it is still not completely understood how and why it gives rise to the various outcomes and clinical presentation of SCA. ( 5 ) Sickle cell anaemia is a red cell disorder, it is however well established that white blood cells (WBC) and platelets play a significant role in the pathophysiology of this disease. Consistent with this, WBC and platelet counts in the steady state can be used together with clinical parameters to predict the outcome of this disorder ( 6 – 8 ). The full blood count (FBC) is the most common investigation performed in medical practice. ( 9 ) It can provide very useful information to assist in diagnosis, management and follow-up when interpreted in relation to the clinical history. Clinicians can be alerted to the presence of a primary haematological disorder by abnormalities in the FBC. It is important to assess not only the current laboratory values but also to establish potential trends over time and in relation to known diagnosis, interventions and treatments. ( 10 ) In the context of SCA, some important haematological parameters include haemoglobin level (Hb), red blood cell count, white blood cell count, platelet count, mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) ( 11 ). The mean values of these parameters in individuals with SCA have been established to be different from those without the condition due to the altered nature of sickle-shaped red blood cells. ( 12 ) However, there are no established reference values for these haematological parameters for SCA, making it difficult for clinicians to interpret and diagnose abnormalities appropriately. ( 13 ) Hence the need for the reference intervals. This study aimed at establishing reference intervals (RIs) for some haematological indices among individuals with SCA. Study Participants The International Federation of Clinical Chemistry Committee on Reference Intervals and Decision Limits (IFCC C-RIDL) on the establishment of reference intervals using the percentile method, recommended a minimum sample size of 120. However, “more is better” to produce robust results ( 14 ) Therefore, we recruited a total of six hundred and seventy-eight (337 males and 341 females) young adults with SCA aged 18–35 years to participate in the study. The subjects were students of a Nigerian tertiary institution originating from six different states (Osun, Oyo, Ogun, Ondo, Ekiti and Lagos) of Southwestern Nigeria and were recruited between February 2018 and August 2023. All the participants were confirmed to be in their steady state. The steady state of the participants was defined as the absence of crisis or any symptoms attributable to acute illness over the preceding four weeks without blood transfusion in the last three months. ( 15 ) Pregnant female participants and subjects not willing to participate were excluded from the study. Ethical consideration Ethical clearance was sorted and obtained from the Ethics and Research Committee of our institution. The aim of the study, the benefits, risks and possible complications of each procedure were carefully explained to each of the participants. Written informed consent was then obtained from each participant before each procedure. Methodology The participants were known patients with Haemoglobin (Hb) SS and the Hb type of each subject was reconfirmed by haemoglobin electrophoresis. This was done using the blood sample collected into an ethylene diamine tetra acetic acid (EDTA) bottle and kept at an alkaline pH of 8.6, following the standard operating procedure (SOP) described in the Helena BioSciences procedure by Monica Ceesbrough, 2008. ( 16 ) The full blood count was done within 6 hours of sample collection using a haematology autoanalyzer (SFRI Blood Cell Counter, H18 Light; France) following standard procedures. The haematological indices were classified using 2.5th and 97.5th percentiles and delineated into low ( 97.5th percentile). All analyses were accomplished using the SPSS version 20.0 statistical package. (SPSS, Chicago, IL, http://www.spss.com ). Results Six hundred and seventy-eight (678) young adults with SCA aged between 18 and 35 years participated in the study and these included 337 males and 341 females giving a male-to-female ratio of 1:1.01. The mean ± SD of the participants was 25.94 ± 4.89 years. As for the haematocrit of the young adults with SCA, the reference interval was 5.2-9.2g/dl, while the WBC ranged between 5.9 to 12.1 x 10 9 /l and the platelet count was found to be between 166 x 10 9 /l and 465 x 10 9 /l. The reference intervals for the other haematological indices are shown in Table 1 below The sex differences in the reference intervals of the haematological indices among the participants are shown in Tables 2 and 3 below. For the male participants, the reference interval of the haematocrit was found to be between 5.2g/dl and 9.3g/dl, while the WBC ranged between 6.7 to 12.1 x 10 9 /l and the platelet count ranged between 166 x 10 9 /l to 399 x 10 9 /l. The female subjects had a haematocrit of between 5.5g/dl to 8.8 g/dl, WBC of between 5.9 10 9 /l and 12.96 x 10 9 /l and their platelet count was between 225 x 10 9 /l and 465 x 10 9 /l. Table 1 Reference Intervals for the Haematological Parameters for Young Adults with Sickle Cell Anaemia Haematology Parameters Lower Limit Upper Limit White Blood Cell (/mm 3 ) 5,900 12,100 Red Blood Cell (/mm 3 ) 2.9 x 10 6 3.5 x 10 6 Haemoglobin (g/dL) 5.2 9.2 Haematocrit (%) 17.8 29.7 Mean Cell Volume (fL) 74.5 105 Mean Cell Haemoglobin (pg) 22.4 37.1 Mean Corpuscular Haemoglobin Concentration (g/dL) 28.3 35.2 Red Distribution Width (%) 14.2 23.3 Platelet (/mm 3 ) 166,000 465,000 N = 678 Table 2 Reference Intervals for the Haematological Parameters for Male Young Adults with Sickle Cell Anaemia Haematology Parameters Lower Limit Upper Limit White Blood Cell (/mm 3 ) 6,700 12,100 Red Blood Cell (/mm 3 ) 2.0 x 10 6 3.5 x10 6 Haemoglobin (g/dL) 5.2 9.3 Haematocrit (%) 17.8 29.9 Mean Cell Volume (fL) 75.7 99.1 Mean Cell Haemoglobin (pg) 23.9 30.0 Mean Corpuscular Haemoglobin Concentration (g/dL) 29.2 32.0 Red Distribution Width (%) 16 23.3 Platelet (/mm 3 ) 166,000 399,000 N = 337 Table 3 Reference Intervals for the Haematological Parameters for Female Young Adults with Sickle cell Anaemia Haematology Parameters Lower Limit Upper Limit White Blood Cell (/mm 3 ) 5,900 12,960 Red Blood Cell (/mm 3 ) 1.9 x 10 6 3.3 x 10 6 Haemoglobin (g/dL) 5.5 8.8 Haematocrit (%) 18.7 28.5 Mean Cell Volume (fL) 74.5 105 Mean Cell Haemoglobin (pg) 22.4 37.1 Mean Corpuscular Haemoglobin Concentration (g/dL) 28.3 35.2 Red Distribution Width (%) 14.2 21.4 Platelet (/mm 3 ) 225,000 465,500 N = 341 Discussion Interpretation of laboratory results requires an appropriate reference interval (RI) supplied by clinical laboratories. Inappropriate RIs can result in misdiagnosis and incorrect patient management. ( 17 ) To guarantee correct evaluations, the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) advise laboratories to develop their RIs. Reference interval takes into account the age, sex, ethnicity and patient population. ( 18 ) Previous studies have established a wide difference in the haematological parameters between individuals with SCA and those without the condition ( 12 ) and there are no established reference values for these haematological parameters for patients with SCA. This descriptive cross-sectional study has established the reference intervals of the haematological indices for young adults with SCA. SCA patients in steady state are preferred because it represent a stable state of disease when there are no recent sickle cell crises or blood transfusions which could interfere with the haematological parameters. ( 15 ) From this study, the reference interval of haematocrit of SCA patients in steady state was found to be between 5.2 to 9.2g/dl, this corresponds to a packed cell volume (PCV) of 15.6 to 27.6%. This finding is similar to the reference interval of 5.0 to 10.6 g/dl reported among SCA aged 18 years and above from earlier report in Tanzania. ( 19 ) A haemoglobin concentration of 8.0-9.5g/dl corresponding to PCV of 24-28.5% was reported by Dami et al among Hb SS and S-β0 thalassemia (S-β0 Thal) patients with age > 18 years old in stable condition in France. ( 20 ) The lower limit of the reference interval observed in our study and the one from Tanzania compared to the value from the Caucasians may be unconnected to the difference in the geographical location and other associated factors such as nutritional status, recurrent infection and socioeconomic status. The observed reference interval of 5.9–12.1 x 10 9 /l and 166–465 x 10 9 /l in this study compared with 4.5–18.9 x 10 9 /l and 149.6-739.8 x 10 9 /l for WBC and platelet respectively reported from Tanzania showed a higher upper limit of normal in the results from Tanzania. The higher steady state WBC and Platelet counts observed in the Tanzanian SCA patients may not be unconnected to the likely differential socioeconomic and educational background of the subjects in both studies. All our subjects are tertiary education students and are likely going to be more informed about their health with better health-seeking behaviours. This will inadvertently reduce the rate of exposure to infections and the prevalence of sickle cell crisis. These differences in the WBC and platelet count between the two populations can be used to predict the severity of the disease in each population because high WBC and platelet counts have been established as surrogate markers of disease severity in SCD. (21&22) The role of genetic factors such as sickle cell haplotypes may need to be investigated as a potential cause of the differences since the patients are from different parts of Africa. Higher WBC has been reported in individuals with SCA even when their steady state is compared with their age and sex-matched counterparts with HB AA. ( 12 ) This has been attributed to many factors such as increased demargination of intravascular neutrophils, increased oxidative stress and the accelerated release from the bone marrow into the circulation in response to haemolysis (23& 24). Some other authors have suggested increased circulating levels of inflammatory cytokines such as interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-) and interferon-gamma (IFN) in SCD patients as a direct cause of increased neutrophil production by the bone marrow. ( 25 ) This increase in total white blood count and neutrophil at steady state has continued to affect the ability of clinicians to predict the presence of bacterial infections from leukocyte counts in SCA patients ( 26 ). Hence, with the established reference intervals, clinicians can now easily identify abnormally high or low WBC and conveniently relate this with the patient's clinical findings to institute appropriate treatment. The platelet count in SCA may be doubled compared with that of individuals with HBAA. ( 12 ) This has been attributed to splenic platelet pool function loss in adults with SCA consequent upon autosplectomy and increased circulating inflammatory mediators ( 27 , 28 ). The high difference in platelet count could also be due to the negative feedback effect on high-level erythropoietin release in response to anaemia, as it has structural homology with thrombopoietin. ( 29 ). Significantly higher WBC and platelet in sickle cell disease have been implicated as a major risk factor for stroke and other sickle cell complications. ( 30 ) A review of the red cell indices of the subjects revealed 74.5-105fl as the reference interval for MCV. The upper limit of 105fl indicates macrocytic anaemia in the general population. ( 31 ) This is not surprising because SCA patients are prone to megaloblastic anaemia due to the increased usage of folic and vitamin B12 due to the haemolysis and are therefore given folate and vitamin B complex as a supplement to prevent this complication. ( 32 ) There was a noticeable difference in reference intervals of some haematological parameters between the male and female subjects notably red cell indices (MCV, MCH and MCHC) and platelet count. According to our research, the platelet count, MCH, MCV, and MCHC in females had greater upper limits than those of their male counterparts. The higher platelet count reported may be unconnected to the increased thrombopoietin secretion in response to the monthly menstrual bleeding in the female cohort however, the role of genetics or hormonal influence may not be underrated. ( 33 ) Previous studies have reported the stimulatory role of oestrogen on megakaryocyte production. Additionally, those researchers showed that estrogen-receptor antagonists inhibited platelet production ( 34 ). Previous studies have reported a significant association between age and MCV but not gender, the observed differences in this study could be related to nutritional differences among the subjects. The adherence rate to routine medications such as folic acid and B-complex by these patients may be the trigger therefore, it needs to be investigated. Conclusion We have established the reference intervals for the haematological indices in young adults with SCA. This will serve as a guide for clinicians to easily interpret the haematological results of patients with SCA and conveniently relate this with the patient's clinical findings to institute appropriate treatment. Declarations Funding This study was not supported by any funding. Conflict of interests The authors declare that they have no conflict of interest. Ethical approval Ethical approval was obtained from the Ethics and Research Committee of the Obafemi Awolowo University (OAU), Ile-Ife. All procedures were performed in accordance with standard guidelines and regulations of OAU Ethics and Research committee and with 1964 Helsinki declaration. Authors’ contributions AMA, BRA and OO contributed to the conception and design of the study. AMA, AIO, AMB, FTA, KSO, BRA and OO obtained the data, analysed and interpreted. AMA, AIO, BRA, and OO drafted the original manuscript. AMA, AIO, AMB, FTA, KSO, BRA and OO critically revised the manuscript. All authors read and approved the final manuscript Informed Consent Informed consent was obtained from all individual participants included in the study Consent for publication Consent for publication was obtained for every individual person’s data included in the study. References Voskaridou l, Dimitrios C, Evangelos T. Sickle-cell anaemia and the heart: review of the current literature. Br. J. Haematol. 2012;157 (6):664–673. Adigwe OP, Onoja SO, Onavbavba G. A critical review of sickle cell disease burden and challenges in sub-Saharan Africa. Journal of Blood Medicine . 2023; 14(1):367-376 Neel, J.V. The Inheritance of Sickle Cell Anemia. Science. 1949; 110(2846):64-66 Tebbi CK. Sickle Cell Disease, a Review. Hemato . 2022; 3(2):341-366 Shah, F. and Dwivedi, M., 2020. Pathophysiology and recent therapeutic insights of sickle cell disease. Annals of Hematology . 2020; 99(1):925-935 Okpala I. The intriguing contribution of white blood cells to sickle cell disease: A red cell disorder. 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Temperature and total white cell count as indicators of bacteraemia. Paediatrics. 1991;87:640–664 Helvaci MR, Tuncsezen UK, Vural A, Onay K, Davran R, Yaprak M, Abyad A, Pocock L. Autosplenectomy may be a good prognostic sign in sickle cell diseases. World Family Med . 2023;21(8):19-32 Shome DK, Jaradat A, Mahozi AI, Sinan AS, Ebrahim A, Alrahim M, Ebraheem MS, Mansoor EJ, Majed KS, Pasha SA. The platelet count and its implications in sickle cell disease patients admitted for intensive care. Indian Journal of Critical Care Medicine . 2018;22(8):585-590 Obeagu EI. Erythropoietin in sickle cell anaemia: a review . International Journal of Research Studies in Medical and Health Sciences. 2020;5(2):22-28. Curtis SA, Danda N, Etzion Z, Cohen HW, Billett HH. Elevated steady state WBC and platelet counts are associated with frequent emergency room use in adults with sickle cell anemia. PLoS One . 2015;10(8):e0133116. Nagao T, Hirokawa M. 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We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5746062","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":398967868,"identity":"fa6e9d44-a790-4003-bc27-4d8e35b3e78f","order_by":0,"name":"Muritala Abiola. 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Kusoro","email":"","orcid":"","institution":"Obafemi Awolowo University Teaching Hospitals Complex","correspondingAuthor":false,"prefix":"","firstName":"Simeon","middleName":"Oluseyi.","lastName":"Kusoro","suffix":""},{"id":398967873,"identity":"fcf39cdf-e367-470f-9123-cfb5370e7d03","order_by":5,"name":"Blessing Toyosi Ogunoye","email":"","orcid":"","institution":"Department of Internal Medicine, Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife Nigeria","correspondingAuthor":false,"prefix":"","firstName":"Blessing","middleName":"Toyosi","lastName":"Ogunoye","suffix":""},{"id":398967874,"identity":"d7f07b12-7adb-4213-80b9-3e06e964b68a","order_by":6,"name":"Oluwadare Ogunlade","email":"","orcid":"","institution":"Obafemi Awolowo University","correspondingAuthor":false,"prefix":"","firstName":"Oluwadare","middleName":"","lastName":"Ogunlade","suffix":""},{"id":398967875,"identity":"f16de418-f7fb-477d-a52b-279e1e365451","order_by":7,"name":"Rahman Ayodele Bolarinwa","email":"","orcid":"","institution":"Obafemi Awolowo University Teaching Hospitals Complex","correspondingAuthor":false,"prefix":"","firstName":"Rahman","middleName":"Ayodele","lastName":"Bolarinwa","suffix":""}],"badges":[],"createdAt":"2025-01-01 12:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5746062/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5746062/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13104-025-07303-2","type":"published","date":"2025-05-26T15:57:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83782900,"identity":"74ed5cf4-ca78-4094-b3e4-3452d068d294","added_by":"auto","created_at":"2025-06-02 16:08:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":598391,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5746062/v1/a5e106e4-95b9-4de2-8238-a3ffccc141d5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reference Intervals of Haematological Indices for Young Adults with Sickle Cell Anaemia in Southwestern Nigeria","fulltext":[{"header":"Background","content":"\u003cp\u003eSickle cell disease (SCD) is considered a global burden, it is predicted to affect approximately 14\u0026nbsp;million newborns by the year 2050 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Currently, Nigeria has the highest burden of the disease. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) SCD refers to a chronic inherited disorder caused by the inheritance of a mutated haemoglobin S gene and another abnormal haemoglobin. The homozygous inheritance of the Hb S gene is referred to as sickle cell anaemia (SCA). The haemoglobin S results from a point mutation which leads to the substitution of glutamic acid for valine at position 6 in the β-globin chain. The resultant Hb S with clinical features arising from the polymerization of this abnormal haemoglobin forming deformed red blood cells with characteristic sickle-shaped. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Although this molecular defect has been known for several decades it is still not completely understood how and why it gives rise to the various outcomes and clinical presentation of SCA. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Sickle cell anaemia is a red cell disorder, it is however well established that white blood cells (WBC) and platelets play a significant role in the pathophysiology of this disease. Consistent with this, WBC and platelet counts in the steady state can be used together with clinical parameters to predict the outcome of this disorder (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe full blood count (FBC) is the most common investigation performed in medical practice. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) It can provide very useful information to assist in diagnosis, management and follow-up when interpreted in relation to the clinical history. Clinicians can be alerted to the presence of a primary haematological disorder by abnormalities in the FBC. It is important to assess not only the current laboratory values but also to establish potential trends over time and in relation to known diagnosis, interventions and treatments. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) In the context of SCA, some important haematological parameters include haemoglobin level (Hb), red blood cell count, white blood cell count, platelet count, mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe mean values of these parameters in individuals with SCA have been established to be different from those without the condition due to the altered nature of sickle-shaped red blood cells. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) However, there are no established reference values for these haematological parameters for SCA, making it difficult for clinicians to interpret and diagnose abnormalities appropriately. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Hence the need for the reference intervals. This study aimed at establishing reference intervals (RIs) for some haematological indices among individuals with SCA.\u003c/p\u003e\n\u003ch3\u003eStudy Participants\u003c/h3\u003e\n\u003cp\u003eThe International Federation of Clinical Chemistry Committee on Reference Intervals and Decision Limits (IFCC C-RIDL) on the establishment of reference intervals using the percentile method, recommended a minimum sample size of 120. However, \u0026ldquo;more is better\u0026rdquo; to produce robust results (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Therefore, we recruited a total of six hundred and seventy-eight (337 males and 341 females) young adults with SCA aged 18\u0026ndash;35 years to participate in the study. The subjects were students of a Nigerian tertiary institution originating from six different states (Osun, Oyo, Ogun, Ondo, Ekiti and Lagos) of Southwestern Nigeria and were recruited between February 2018 and August 2023. All the participants were confirmed to be in their steady state. The steady state of the participants was defined as the absence of crisis or any symptoms attributable to acute illness over the preceding four weeks without blood transfusion in the last three months. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Pregnant female participants and subjects not willing to participate were excluded from the study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthical consideration\u003c/h2\u003e \u003cp\u003e Ethical clearance was sorted and obtained from the Ethics and Research Committee of our institution. The aim of the study, the benefits, risks and possible complications of each procedure were carefully explained to each of the participants. Written informed consent was then obtained from each participant before each procedure.\u003c/p\u003e \u003c/div\u003e"},{"header":"Methodology","content":"\u003cp\u003eThe participants were known patients with Haemoglobin (Hb) SS and the Hb type of each subject was reconfirmed by haemoglobin electrophoresis. This was done using the blood sample collected into an ethylene diamine tetra acetic acid (EDTA) bottle and kept at an alkaline pH of 8.6, following the standard operating procedure (SOP) described in the Helena BioSciences procedure by Monica Ceesbrough, 2008. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe full blood count was done within 6 hours of sample collection using a haematology autoanalyzer (SFRI Blood Cell Counter, H18 Light; France) following standard procedures. The haematological indices were classified using 2.5th and 97.5th percentiles and delineated into low (\u0026lt;\u0026thinsp;2.5th percentile), normal reference interval (2.5\u0026ndash;97.5th percentile) and high (\u0026gt;\u0026thinsp;97.5th percentile). All analyses were accomplished using the SPSS version 20.0 statistical package. (SPSS, Chicago, IL, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.spss.com\u003c/span\u003e\u003cspan address=\"http://www.spss.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSix hundred and seventy-eight (678) young adults with SCA aged between 18 and 35 years participated in the study and these included 337 males and 341 females giving a male-to-female ratio of 1:1.01. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of the participants was 25.94\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89 years.\u003c/p\u003e \u003cp\u003eAs for the haematocrit of the young adults with SCA, the reference interval was 5.2-9.2g/dl, while the WBC ranged between 5.9 to 12.1 x 10\u003csup\u003e9\u003c/sup\u003e/l and the platelet count was found to be between 166 x 10\u003csup\u003e9\u003c/sup\u003e/l and 465 x 10\u003csup\u003e9\u003c/sup\u003e/l. The reference intervals for the other haematological indices are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e below\u003c/p\u003e \u003cp\u003eThe sex differences in the reference intervals of the haematological indices among the participants are shown in Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e below.\u003c/p\u003e \u003cp\u003eFor the male participants, the reference interval of the haematocrit was found to be between 5.2g/dl and 9.3g/dl, while the WBC ranged between 6.7 to 12.1 x 10\u003csup\u003e9\u003c/sup\u003e/l and the platelet count ranged between 166 x 10\u003csup\u003e9\u003c/sup\u003e/l to 399 x 10\u003csup\u003e9\u003c/sup\u003e/l.\u003c/p\u003e \u003cp\u003eThe female subjects had a haematocrit of between 5.5g/dl to 8.8 g/dl, WBC of between 5.9 10\u003csup\u003e9\u003c/sup\u003e/l and 12.96 x 10\u003csup\u003e9\u003c/sup\u003e/l and their platelet count was between 225 x 10\u003csup\u003e9\u003c/sup\u003e/l and 465 x 10\u003csup\u003e9\u003c/sup\u003e/l.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReference Intervals for the Haematological Parameters for Young Adults with Sickle Cell Anaemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematology Parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower Limit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUpper Limit\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12,100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 x 10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 x 10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematocrit (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Volume (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Haemoglobin (pg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Corpuscular Haemoglobin Concentration (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Distribution Width (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e465,000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eN = 678\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReference Intervals for the Haematological Parameters for Male Young Adults with Sickle Cell Anaemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematology Parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower Limit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUpper Limit\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12,100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0 x 10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 x10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematocrit (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Volume (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Haemoglobin (pg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Corpuscular Haemoglobin Concentration (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Distribution Width (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e399,000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eN = 337\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReference Intervals for the Haematological Parameters for Female Young Adults with Sickle cell Anaemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematology Parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower Limit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUpper Limit\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12,960\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Blood Cell (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.9 x 10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.3 x 10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematocrit (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Volume (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Cell Haemoglobin (pg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Corpuscular Haemoglobin Concentration (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed Distribution Width (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet (/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e225,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e465,500\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eN\u0026thinsp;=\u0026thinsp;341\u003c/h2\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eInterpretation of laboratory results requires an appropriate reference interval (RI) supplied by clinical laboratories. Inappropriate RIs can result in misdiagnosis and incorrect patient management. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) To guarantee correct evaluations, the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) advise laboratories to develop their RIs. Reference interval takes into account the age, sex, ethnicity and patient population. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Previous studies have established a wide difference in the haematological parameters between individuals with SCA and those without the condition (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) and there are no established reference values for these haematological parameters for patients with SCA. This descriptive cross-sectional study has established the reference intervals of the haematological indices for young adults with SCA. SCA patients in steady state are preferred because it represent a stable state of disease when there are no recent sickle cell crises or blood transfusions which could interfere with the haematological parameters. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) From this study, the reference interval of haematocrit of SCA patients in steady state was found to be between 5.2 to 9.2g/dl, this corresponds to a packed cell volume (PCV) of 15.6 to 27.6%. This finding is similar to the reference interval of 5.0 to 10.6 g/dl reported among SCA aged 18 years and above from earlier report in Tanzania. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) A haemoglobin concentration of 8.0-9.5g/dl corresponding to PCV of 24-28.5% was reported by Dami et al among Hb SS and S-β0 thalassemia (S-β0 Thal) patients with age\u0026thinsp;\u0026gt;\u0026thinsp;18 years old in stable condition in France. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) The lower limit of the reference interval observed in our study and the one from Tanzania compared to the value from the Caucasians may be unconnected to the difference in the geographical location and other associated factors such as nutritional status, recurrent infection and socioeconomic status. The observed reference interval of 5.9\u0026ndash;12.1 x 10\u003csup\u003e9\u003c/sup\u003e/l and 166\u0026ndash;465 x 10\u003csup\u003e9\u003c/sup\u003e/l in this study compared with 4.5\u0026ndash;18.9 x 10\u003csup\u003e9\u003c/sup\u003e/l and 149.6-739.8 x 10\u003csup\u003e9\u003c/sup\u003e/l for WBC and platelet respectively reported from Tanzania showed a higher upper limit of normal in the results from Tanzania. The higher steady state WBC and Platelet counts observed in the Tanzanian SCA patients may not be unconnected to the likely differential socioeconomic and educational background of the subjects in both studies. All our subjects are tertiary education students and are likely going to be more informed about their health with better health-seeking behaviours. This will inadvertently reduce the rate of exposure to infections and the prevalence of sickle cell crisis. These differences in the WBC and platelet count between the two populations can be used to predict the severity of the disease in each population because high WBC and platelet counts have been established as surrogate markers of disease severity in SCD. (21\u0026amp;22) The role of genetic factors such as sickle cell haplotypes may need to be investigated as a potential cause of the differences since the patients are from different parts of Africa. Higher WBC has been reported in individuals with SCA even when their steady state is compared with their age and sex-matched counterparts with HB AA. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) This has been attributed to many factors such as increased demargination of intravascular neutrophils, increased oxidative stress and the accelerated release from the bone marrow into the circulation in response to haemolysis (23\u0026amp; 24). Some other authors have suggested increased circulating levels of inflammatory cytokines such as interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-) and interferon-gamma (IFN) in SCD patients as a direct cause of increased neutrophil production by the bone marrow. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) This increase in total white blood count and neutrophil at steady state has continued to affect the ability of clinicians to predict the presence of bacterial infections from leukocyte counts in SCA patients (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Hence, with the established reference intervals, clinicians can now easily identify abnormally high or low WBC and conveniently relate this with the patient's clinical findings to institute appropriate treatment. The platelet count in SCA may be doubled compared with that of individuals with HBAA. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) This has been attributed to splenic platelet pool function loss in adults with SCA consequent upon autosplectomy and increased circulating inflammatory mediators (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The high difference in platelet count could also be due to the negative feedback effect on high-level erythropoietin release in response to anaemia, as it has structural homology with thrombopoietin. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Significantly higher WBC and platelet in sickle cell disease have been implicated as a major risk factor for stroke and other sickle cell complications. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) A review of the red cell indices of the subjects revealed 74.5-105fl as the reference interval for MCV. The upper limit of 105fl indicates macrocytic anaemia in the general population. (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) This is not surprising because SCA patients are prone to megaloblastic anaemia due to the increased usage of folic and vitamin B12 due to the haemolysis and are therefore given folate and vitamin B complex as a supplement to prevent this complication. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere was a noticeable difference in reference intervals of some haematological parameters between the male and female subjects notably red cell indices (MCV, MCH and MCHC) and platelet count. According to our research, the platelet count, MCH, MCV, and MCHC in females had greater upper limits than those of their male counterparts. The higher platelet count reported may be unconnected to the increased thrombopoietin secretion in response to the monthly menstrual bleeding in the female cohort however, the role of genetics or hormonal influence may not be underrated. (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) Previous studies have reported the stimulatory role of oestrogen on megakaryocyte production. Additionally, those researchers showed that estrogen-receptor antagonists inhibited platelet production (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Previous studies have reported a significant association between age and MCV but not gender, the observed differences in this study could be related to nutritional differences among the subjects. The adherence rate to routine medications such as folic acid and B-complex by these patients may be the trigger therefore, it needs to be investigated.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have established the reference intervals for the haematological indices in young adults with SCA. This will serve as a guide for clinicians to easily interpret the haematological results of patients with SCA and conveniently relate this with the patient's clinical findings to institute appropriate treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Ethics and Research Committee of the Obafemi Awolowo University (OAU), Ile-Ife. All procedures were performed in accordance with standard guidelines and regulations of OAU Ethics and Research committee and with 1964 Helsinki declaration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAMA, BRA and OO contributed to the conception and design of the study. AMA, AIO, AMB, FTA, KSO, BRA and OO obtained the data, analysed and interpreted. AMA, AIO, BRA, and OO drafted the original manuscript. AMA, AIO, AMB, FTA, KSO, BRA and OO critically revised the manuscript. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained for every individual person’s data included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVoskaridou l, Dimitrios C, Evangelos T. Sickle-cell anaemia and the heart: review of the current literature.\u003cem\u003e Br. J. Haematol.\u003c/em\u003e 2012;157 (6):664\u0026ndash;673.\u003c/li\u003e\n\u003cli\u003eAdigwe OP, Onoja SO, Onavbavba G. A critical review of sickle cell disease burden and challenges in sub-Saharan Africa. \u003cem\u003eJournal of Blood Medicine\u003c/em\u003e. 2023; 14(1):367-376\u003c/li\u003e\n\u003cli\u003eNeel, J.V. 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Platelet count as a predictor of the severity of sickle cell disease during pregnancy. \u003cem\u003eJ Obstet Gynaecol\u003c/em\u003e 2008;28(7):688‑691\u003c/li\u003e\n\u003cli\u003eLeach M. Interpretation of the full blood count in systemic disease\u0026ndash;a guide for the physician. \u003cem\u003eJR Coll Physicians Edinb\u003c/em\u003e. 2014;44(1):36-41\u003c/li\u003e\n\u003cli\u003eVirdee PS, Marian IR, Mansouri A, Elhussein L, Kirtley S, Holt T, Birks J. The full blood count blood test for colorectal cancer detection: a systematic review, meta-analysis, and critical appraisal. \u003cem\u003eCancers\u003c/em\u003e. 2020;12(9):1-37\u003c/li\u003e\n\u003cli\u003eFasola FA, Adekanmi AJ. Haematological profile and blood transfusion pattern of patients with sickle cell anaemia vary with spleen size. \u003cem\u003eAnnals of Ibadan postgraduate medicine\u003c/em\u003e. 2019;17(1):30-38.\u003c/li\u003e\n\u003cli\u003eAsafa MA, Ahmed IO, Umar AS, Bolarinwa RA, Ogunlade O. 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Hematological and biochemical reference ranges for the population with sickle cell disease at steady state in Tanzania. \u003cem\u003eHemato.\u003c/em\u003e 2022;3(1):82-97.\u003c/li\u003e\n\u003cli\u003eDamy T, Bodez D, Habibi A, Guellich A, Rappeneau S, Inamo J, Guendouz S, Gellen-Dautremer J, Pissard S, Loric S, Wagner-Ballon O. Haematological determinants of cardiac involvement in adults with sickle cell disease. \u003cem\u003eEuropean Heart Journal\u003c/em\u003e. 2016;37(14):1158-1167\u003c/li\u003e\n\u003cli\u003eAlsalman M. Laboratory predictors of sickle cell disease severity: a cross-sectional study. \u003cem\u003eJournal of Medicine and Life\u003c/em\u003e. 2024;17(1):63-66\u003c/li\u003e\n\u003cli\u003eHelvaci MR, Aydogan F, Sevinc A, Camci C, Dilek I. Platelet and white blood cell counts in severity of sickle cell diseases. \u003cem\u003eHealthMED\u003c/em\u003e. 2014;8(4):477-482.\u003c/li\u003e\n\u003cli\u003eIfeanyi OE, Nwakaego OB, Angela IO, Nwakaego CC. Haematological parameters among sickle cell anaemia patients in steady state and haemoglobin genotype AA individuals at Michael Okpara, University of Agriculture, Umudike, Abia State, Nigeria. \u003cem\u003eInt J Curr Microbiol Appl Sci\u003c/em\u003e 2014; 3:1000\u0026ndash;1005\u003c/li\u003e\n\u003cli\u003ePiel FB, Williams TN. Subphenotypes of sickle cell disease in Africa. Blood 2017;130:2157\u0026ndash;2158\u003c/li\u003e\n\u003cli\u003eConran N, Belcher JD. Inflammation in sickle cell disease. \u003cem\u003eClinical hemorheology and microcirculation\u003c/em\u003e. 2018;68(2):263-299\u003c/li\u003e\n\u003cli\u003eJaffe DM, Fleisher GR. Temperature and total white cell count as indicators of bacteraemia. \u003cem\u003ePaediatrics.\u003c/em\u003e 1991;87:640\u0026ndash;664\u003c/li\u003e\n\u003cli\u003eHelvaci MR, Tuncsezen UK, Vural A, Onay K, Davran R, Yaprak M, Abyad A, Pocock L. Autosplenectomy may be a good prognostic sign in sickle cell diseases. \u003cem\u003eWorld Family Med\u003c/em\u003e. 2023;21(8):19-32\u003c/li\u003e\n\u003cli\u003eShome DK, Jaradat A, Mahozi AI, Sinan AS, Ebrahim A, Alrahim M, Ebraheem MS, Mansoor EJ, Majed KS, Pasha SA. The platelet count and its implications in sickle cell disease patients admitted for intensive care. \u003cem\u003eIndian Journal of Critical Care Medicine\u003c/em\u003e. 2018;22(8):585-590\u003c/li\u003e\n\u003cli\u003eObeagu EI. Erythropoietin in sickle cell anaemia: a review\u003cem\u003e. International Journal of Research Studies in Medical and Health Sciences.\u003c/em\u003e 2020;5(2):22-28.\u003c/li\u003e\n\u003cli\u003eCurtis SA, Danda N, Etzion Z, Cohen HW, Billett HH. Elevated steady state WBC and platelet counts are associated with frequent emergency room use in adults with sickle cell anemia. \u003cem\u003ePLoS One\u003c/em\u003e. 2015;10(8):e0133116.\u003c/li\u003e\n\u003cli\u003eNagao T, Hirokawa M. Diagnosis and treatment of macrocytic anemias in adults. \u003cem\u003eJournal of general and family medicine\u003c/em\u003e. 2017;18(5):200-204\u003c/li\u003e\n\u003cli\u003ePatel S, Bhaumik S. Sickle cell disease and folate supplementation. \u003cem\u003ePanacea J Med Sci.\u003c/em\u003e 2019;9(2):39-42.\u003c/li\u003e\n\u003cli\u003eButkiewicz AM, Kemona H, Dymicka-Piekarska V, Matowicka-Karna J, Radziwon P, Lipska A. Platelet count, mean platelet volume and thrombocytopoietic indices in healthy women and men. \u003cem\u003eThrombosis research\u003c/em\u003e. 2006;118(2):199-204.\u003c/li\u003e\n\u003cli\u003eSegal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. \u003cem\u003eAnnals of epidemiology\u003c/em\u003e. 2006;16(2):123-130.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-research-notes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"resn","sideBox":"Learn more about [BMC Research Notes](http://bmcresnotes.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/resn/default.aspx","title":"BMC Research Notes","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sickle cell anaemia, Haematological indices, reference values, young adults","lastPublishedDoi":"10.21203/rs.3.rs-5746062/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5746062/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eReference intervals (RIs) are crucial for the interpretation of results and overall patient management. Of note, there are no established reference values for haematological parameters for patients with sickle cell anaemia (SCA) in Nigeria, making it difficult for clinicians to interpret and diagnose abnormalities appropriately.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed at establishing RIs of some haematological indices for individuals with SCA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis descriptive cross-sectional study, included a total of six hundred and seventy-eight (337 males and 341 females) young adults with SCA aged 18\u0026ndash;35 years. The full blood count (FBC) was done using a haematology autoanalyzer. The haematological indices were classified using 2.5th and 97.5th percentiles and delineated as low (\u0026lt;\u0026thinsp;2.5th percentile), normal reference interval (2.5\u0026ndash;97.5th percentile) and high (\u0026gt;\u0026thinsp;97.5th percentile). All analyses were done using SPSS IBM, version 20.0 software\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eGenerally, the reference interval for Haematocrit is 5.2-9.2g/dl, while the WBC ranged between 5.9 to 12.1 x 10\u003csup\u003e9\u003c/sup\u003e/l and the platelet count is 166\u0026ndash;465 x 10\u003csup\u003e9\u003c/sup\u003e/l. For the male participants, the reference interval of the haematocrit was found to be between 5.2-9.3g/dl, the WBC ranged between 6.7 to 12.1 x 10\u003csup\u003e9\u003c/sup\u003e/l and the platelet count was between 166 x 10\u003csup\u003e9\u003c/sup\u003e/l to 399 x 10\u003csup\u003e9\u003c/sup\u003e/l. The female subjects had a haematocrit of between 5.5g/dl to 8.8 g/dl, WBC of between 5.9 10\u003csup\u003e9\u003c/sup\u003e/l and 12.96 x 10\u003csup\u003e9\u003c/sup\u003e/l and the platelet count was between 225 x 10\u003csup\u003e9\u003c/sup\u003e/l and 465 x 10\u003csup\u003e9\u003c/sup\u003e/l.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study has established the reference intervals for the haematological indices in individuals with SCA\u003c/p\u003e","manuscriptTitle":"Reference Intervals of Haematological Indices for Young Adults with Sickle Cell Anaemia in Southwestern Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-08 06:01:07","doi":"10.21203/rs.3.rs-5746062/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-02-03T11:50:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-01T22:32:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97331819127147958373859693298026422906","date":"2025-01-27T20:52:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-20T20:04:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70608896942752761548552524837928921862","date":"2025-01-16T17:50:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-16T15:39:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-01-06T15:13:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-06T12:42:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-06T12:41:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Research Notes","date":"2025-01-01T12:00:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-research-notes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"resn","sideBox":"Learn more about [BMC Research Notes](http://bmcresnotes.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/resn/default.aspx","title":"BMC Research Notes","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3312d23d-7e5b-4558-9e9f-cbcd66b1b493","owner":[],"postedDate":"January 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-02T16:01:34+00:00","versionOfRecord":{"articleIdentity":"rs-5746062","link":"https://doi.org/10.1186/s13104-025-07303-2","journal":{"identity":"bmc-research-notes","isVorOnly":false,"title":"BMC Research Notes"},"publishedOn":"2025-05-26 15:57:31","publishedOnDateReadable":"May 26th, 2025"},"versionCreatedAt":"2025-01-08 06:01:07","video":"","vorDoi":"10.1186/s13104-025-07303-2","vorDoiUrl":"https://doi.org/10.1186/s13104-025-07303-2","workflowStages":[]},"version":"v1","identity":"rs-5746062","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5746062","identity":"rs-5746062","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}