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Year : 2023  |  Volume : 22  |  Issue : 1  |  Page : 70-76  

Iron supplementation and blood donation in Nigeria: Effect on Hemoglobin, red cell indices, and iron stores – The ranferon™ study

1 Department of Haematology and Immunology, College of Medicine, University of Nigeria, Ituku/Ozalla Campus, Nsukka, Nigeria
2 Department of Medical Laboratory Services, National Orthopedic Hospital, Enugu, Enugu State, Nigeria

Date of Submission03-Dec-2021
Date of Decision17-Jan-2022
Date of Acceptance17-May-2022
Date of Web Publication24-Jan-2023

Correspondence Address:
Angela Ogechukwu Ugwu
Department of Haematology and Immunology, College of Medicine, University of Nigeria, Ituku/Ozalla Campus, Nsukka, Enugu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aam.aam_248_21

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Background: Iron-deficiency anemia is an important limiting factor to a sustainable supply of blood units, especially in low- and middle-income countries. Blood transfusion practice in Nigeria is poorly developed and structured with paucity of voluntary nonremunerated blood donors and high rate of donor deferrals resulting from low hemoglobin (Hb) levels. Aims: This study aimed to assess the effect of daily supplementation of iron using Ranferon-12 on Hb level, red blood cell (RBC) indices, iron level, ferritin level, and Hb recovery in blood donors in Nigeria. Methodology: This longitudinal study was conducted at a tertiary hospital blood transfusion center from March to July 2020. Blood samples of regular donors were collected at three points in the study for the measurement of Hb and hematocrit (HCT); RBC indices including mean cell volume (MCV), mean cell hemoglobin (MCH), and Mean cell haemoglobin concentration (MCHC); and iron stores including serum iron, serum ferritin, and serum transferrin. The first point was at recruitment before donation of one unit of blood; the second point after the blood donation; and the third point at 6 weeks post blood donation. Following donation, participants were placed on Ranferon capsules (iron fumarate - 100 mg elemental iron) and 100 mg of tablet Vitamin C, for 6 weeks. Results: There was a moderate significant positive correlation between administration of Ranferon and change in the values of HCT, MCV, MCH, red cell distribution width, ferritin, and transferring (P < 0.05). Percentage recovery of Hb, red cell indices, and iron stores parameters after 6 weeks of daily Ranferon ranged between 89% and 100%. Conclusion: Iron supplementation using Ranferon capsule daily for 6 weeks enhances recovery of Hb, red cell indices, and iron stores with attainment of benchmark Hb levels for donation.

   Abstract in French 

Contexte: L'anémie ferriprive est un facteur limitant important pour un approvisionnement durable en unités de sang, en particulier dans les pays à revenu faible et intermédiaire (PRFI). La pratique de la transfusion sanguine au Nigéria est peu développée et structurée avec une pénurie de donneurs de sang volontaires non rémunérés (VNRD) et un taux élevé d'exclusion des donneurs résultant de faibles taux d'hémoglobine (Hb). Objectifs: Cette étude visait à évaluer l'effet de la supplémentation quotidienne en fer à l'aide de Ranferon-12 sur le taux d'hémoglobine (Hb), les indices de globules rouges (RBC), le taux de fer, le taux de ferritine et la récupération de l'Hb chez les donneurs de sang au Nigeria. Méthodes: Cette étude longitudinale a été menée dans un centre de transfusion sanguine d'un hôpital tertiaire de mars à juillet 2020. Des échantillons de sang de donneurs réguliers ont été prélevés à trois points de l'étude pour mesurer l'Hb, l'hématocrite (HCT) ; Les indices RBC, y compris le volume cellulaire moyen (MCV), l'hémoglobine cellulaire moyenne (MCH) et la concentration moyenne d'hémoglobine cellulaire (MCHC) ; et les réserves de fer, y compris le fer sérique, la ferritine sérique et la transferrine sérique. Le premier point concernait le recrutement avant le don d'une unité de sang ; deuxième point – après le don de sang ; et troisième point – six semaines après le don de sang. Après le don, les participants ont reçu des gélules de Ranferon (fumarate de fer --100 mg de fer élémentaire) et 100 mg de vitamine C en comprimé, pendant 6 semaines. Résultats: Il y avait une corrélation positive significative modérée entre l'administration de Ranferon et le changement des valeurs de HCT, MCV, MCH, la largeur de distribution des globules rouges, la ferritine et le transfert (p < 0,05). Le pourcentage de récupération de l'Hb, des indices de globules rouges et des paramètres des réserves de fer après 6 semaines de Ranferon quotidien variait entre 89 % et 100 %. Conclusion: La supplémentation en fer à l'aide de la capsule de Ranferon quotidiennement pendant 6 semaines améliore la récupération de l'Hb, des indices de globules rouges et des réserves de fer avec l'atteinte des niveaux d'hémoglobine de référence pour le don.
Mots-clés: Transfusion sanguine, donneurs de sang, ferritine, hémoglobine, anémie ferriprive

Keywords: Blood donors, blood transfusion, ferritin, hemoglobin, Iron-deficiency anemia

How to cite this article:
Nwagha TU, Ugwu AO, Nwaekpe CN. Iron supplementation and blood donation in Nigeria: Effect on Hemoglobin, red cell indices, and iron stores – The ranferon™ study. Ann Afr Med 2023;22:70-6

How to cite this URL:
Nwagha TU, Ugwu AO, Nwaekpe CN. Iron supplementation and blood donation in Nigeria: Effect on Hemoglobin, red cell indices, and iron stores – The ranferon™ study. Ann Afr Med [serial online] 2023 [cited 2023 Jan 29];22:70-6. Available from:

   Introduction Top

Regular blood donation prevents the formation of free radicals by inhibiting the accumulation of iron;[1] in this same light, chronic iron deficiency commonly results from regular blood donation.[2] Iron is depleted in regular blood donation with substantial loss of 200–250 mg of iron at each donation. It is estimated that 25% to 35% of blood donors become iron depleted from regular blood donation.[3],[4] If not compensated for efficiently, the iron loss may eventually lead to anemia, an important limiting factor to a sustainable supply of blood units.

In developed countries, low Hb represents the single largest reason of blood donor deferral and women are mostly affected.[5] Whereas, in low- and middle-income countries (LMIC) like Nigeria, testing positive to transfusion transmissible infections and hypertension were the most common with low Hb being third most common reason for deferrals.[6]

A Study done in Calabar, Nigeria, showed that some blood donors are in prelatent and latent iron deficiency state at the time of blood donation and hence recommended iron supplementation as an intervention.[7] Similarly, a study done in Port Harcourt, Nigeria, put the prevalence of anemia among blood donors to be 13.7% and iron-deficiency anemia 12%,[8] while another study done in Sokoto reported a high prevalence rate 24% for iron deficiency among blood donors, with low ferritin levels seen more in family replacement donors than voluntary donors.[9] Both studies called for iron supplementation to protect the vulnerable donor population.[8],[9]

Available evidence shows that iron supplementation post donation improves iron status, restores hemoglobin (Hb), and prevents donor deferrals.[5],[10] This intervention would be of immense benefit to blood donation practice in LMICs like Nigeria where there is need to explore avenues to maintain healthy Hb and iron levels among blood donors. This will protect the dwindling and overburdened blood-donor population and ultimately facilitate a robust and sustainable blood supply in our blood banks.

This study, hence, aimed to evaluate the use of daily iron supplementation as an intervention to improve the Hb recovery time in frequent blood donors after donation of a unit of blood at transfusion center in South East Nigeria.

   Methodology Top

This longitudinal study was conducted in a tertiary health facility in Enugu, South East Nigeria, between March and July 2020. The study center was the blood transfusion center of the university teaching hospital. The hospital has an annual average 'blood donation' of 3500 units.

Ethical clearance

The ethical clearance for the study was obtained from the Institutional Research and Ethics Committee (approval number: NHREC/05/01/2008B-FWA00002458-1RB00002323). Written informed consent was obtained from all the participants before recruitment into the study.

Study participants

The study participants were blood donors at the blood donation unit of the hospital's transfusion center. All regular blood donors aged 18–65 years who were eligible for the study were consecutively selected for the study. Exclusion criteria included individuals of either sex, who were on iron supplements including multivitamins containing iron and refused to stop doing so for the 6 weeks of the study, and those with baseline ferritin >300 ug/L, which was done to exclude individuals with hemochromatosis.

Sampling method

The nonprobability sampling method was used. Eligible participants were consecutively recruited as they come for blood donation. The recruitment was based on their willingness to donate blood voluntarily.

Study intervention

The participants for this study were placed on daily iron supplement using Ranferon capsule containing 305 mg ferrous fumarate equivalent to 100 mg elemental iron, cyanocobalamin 5 μg, folic acid 0.75 mg, and zinc sulfate 5 mg following successful donation of one unit of blood. The participants received one capsule of Ranferon and 100 mg of ascorbic acid daily for 6 weeks.

Blood samples were collected from all the eligible participants at three points in the study. First, at the point of recruitment into the study before donation of a unit of blood; second point was soon after donation of a unit of blood and the third point was six weeks after blood donation. At these three points, the collected blood samples were assayed for the following investigations: Hb level, hematocrit (HCT) packed cell volume (PCV), red cell indices (mean cell volume [MCV], mean cell hemoglobin [MCH], and mean cell hemoglobin concentration [MCHC]), and iron stores (serum iron, serum % iron saturation, serum ferritin, and serum transferrin). Data were also collected regarding the side effects of the Ranferon iron therapy and compliance/adherence to the therapy.

Outcome measures

The primary outcome measures were the mean levels of Hb, PCV, MCV, MCH, MCHC, serum iron, serum % iron saturation, serum ferritin, and serum transferrin. The secondary outcomes were level of drug adherence, compliance, and any self-reported side effects of the Ranferon iron therapy.

Specimen collection and preparation

The first 2 ml of blood was drawn into a sodium ethylenediaminetetraacetic acid specimen bottle for a full blood count, including red blood cell indices (MCV), mean corpuscular hemoglobin (MCHC), MCH, and red cell distribution width (RDW) using the Mythic 22 haematology analyzer. They were analyzed in batches within two hours of collection.

The remaining 8 ml of blood was drawn into serum separator tubes. This was subsequently centrifuged, and the serum was then separated, transferred to plain cryotubes using a transfer pipette, and stored at −20°C until analysis. This was used to measure serum ferritin, serum iron, and serum transferrin receptor levels. Serum ferritin assay was done using Abbott i1000sr immune analyzer, total body iron was assayed using Beckman coulter AU680 chemistry analyzer, and soluble transferrin receptor was analyzed using Nephelometery. Percentage iron saturation was calculated using this formula: (Serum iron level × 100)/total iron-binding capacity).

Data collection

Relevant donor characteristics: age, gender, occupation, history of blood donation, and history of hypertension and/or diabetes mellitus were recorded in the case report form. Adherence and compliance to the iron supplements was recorded using Morisky medication adherence scale.[11] Questions were restructured to prevent a “yes saying” bias. The responses were “yes” or “no” for numbers 1–5. Question number 6 which was on refilling the medication was omitted as participants were given supplements for 6 weeks. Each “no” response was rated 1 and the “yes” was rated 0. Questions 1–3 tested motivation to adhere to the medication, while for questions 4 and 5, the “yes” response was rated 1 and “no” was 0. This tested knowledge of discontinuing medication without guidance. The total scores were put as 0–1 = Low motivation, 2–3 = High motivation, 0–1 = Low knowledge, and 2–3 = High knowledge.

Statistical analysis

Statistical analyses were conducted using Statistical Package for the Social Sciences for Windows version 22 software (SPSS Inc, Chicago, IL, USA). Descriptive statistics was used to compute frequencies and percentages. Continuous variables were analyzed using either the Student's t-test or Mann–Whitney U-test depending on the distribution of the data. Discrete variables were analyzed using Chi-square, and the Pearson's correlation coefficient was also done. The critical level of statistical significance was set at P < 0.05.

   Results Top

Sociodemographic characteristics

A total of 90 healthy regular blood donors were enrolled into the study. The overall mean age of the study participants was 27 ± 7 years old. The majority of the study participants (52.2%) were less than 24 years old, while the minority (2.2%) were above 45 years old. Most of the participants (95.6%) were male. The majority (95%) of the study participants were single. The details are shown in [Table 1].
Table 1: Sociodemographic characteristics of the study participants

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Baseline hematological profile and iron studies of participants before blood donation

The mean Hb, HCT, MCV, and MCH values for the participants were 15.46 ± 2.96 g/dl, 40.03 ± 3.140 L/L, 83.78 ± 7.09 fl, and 28.37 ± 4.28 pg, respectively [Table 2]. The mean values recorded for serum ferritin and serum transferrin were 77.86 ± 44.43 ng/ml and 2.77 ± 0.26 g/L, respectively. The details are shown in [Table 2].
Table 2: Baseline mean hemoglobin, hematocrit, red cell indices, and iron parameters of the participants before blood donation

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Hematological profile and iron studies at post-6 weeks administration of Ranferon capsule

The mean Hb, HCT, MCV, and MCH values for the participants post-6 weeks administration with 100 mg elemental iron (Ranferon capsule) were 13.74 ± 1.25 g/dl, 40.41 ± 3.94 L/L, 83.39 ± 6.86 fL, and 28.43 ± 2.95 pg, respectively. The mean values recorded for serum ferritin and serum transferrin were 77.86 ± 44.43 ng/ml, and 2.77 ± 0.26 g/L respectively. The correlation between RBC count, Hb, HCT, and red cell indices at point 3 (6 weeks post-intervention) and point 2 (immediate post-donation ) were as shown in [Table 3]. Following 6 weeks postadministration of Ranferon capsule, participants' changes in red cell parameters were 11.1% decrease in Hb level, 1.0% increase in HCT value, 0.5% decrease in MCV, 0.0% change in MCH, 0.9% decrease in MCHC, 20.3% increase in serum iron, 1.5.1 increase in serum ferritin, and a 17.1% increase in percentage saturation. The details are shown in [Table 4].
Table 3: Comparison of complete blood count at 6 weeks post-Ranferon intervention (point 3) versus immediately after blood donation (point 2)

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Table 4: Percent recovery of hemoglobin, red cell indices, and iron studies parameters 6 weeks postintervention

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Association between administration of iron and its effects on red cell parameters

There was a moderate significant positive correlation between administration of elemental iron and change in the values of HCT, mean corpuscular volume, and RDW (r = 0.45, P = 0.00; r = 0.49, P = 0.00; and r = 0.60, P = 0.00, respectively). There was a weak significant correlation between the administration of iron and changes in MCH, ferritin, and transferrin (r = 0.45, P = 0.00; r = 0.49, P = 0.00; and r = 0.60, P = 0.00, respectively). The details are shown in [Table 5].
Table 5: Correlation between iron supplementation and its effects on hematological parameters (pre- and post-Ranferon intervention)

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Compliance, adherence, and side effect profile of iron supplementation using Ranferon

Elemental iron was well tolerated by most of the study participants as there was only one report of vomiting, diarrhea, and abdominal discomfort (1.7%), respectively [Table 6]. Majority complied and adhered to daily intake of iron. Based on modified Morisky scale, 78% had high motivation to adhere to iron supplementation, while 88% knew the benefits of adhere to supplementation. The details are shown in [Table 7].
Table 6: Adherence and compliance using modified Morisky Scale

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Table 7: Frequency of complications reported by the study participants postintervention

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   Discussion Top

This study has revealed that after 6 weeks postintervention with iron supplementation using Ranferon, there were significant differences in the levels of the soluble transferrin, red cell count, and red cell indices (P < 0.001), and these variables could be possible indicators of recovery of erythropoiesis postblood donation. Two Indian studies showed that MCV and MCH can be possible indicators of iron deficiency in repeat blood donors.[12],[13] One may propose that red cell indices such as MCV and MCH could be early indicators of recovery while on iron supplementation postblood donation. Future studies are, however, needed to answer this question.

This study also showed notable increases in the percent recovery of all red cell variables and iron study variables after 6 weeks postintervention with iron supplementation using Ranferon. Observation from the present study was that with 11.1% recovery of hemoglobin levels among study participants, 93.3% of our test participants still met the Hb level eligibility criteria to safely donate another unit of blood after 6 weeks on Ranferon. This is comparable to findings from the HEIRS study which showed iron supplementation increased percent recovery of Hb levels, red cell indices, and iron study parameters postdonation.[5]

This study reported a positive significant correlation with red cell indices and iron supplementation. It also reiterates the benefits of 6 weeks daily iron supplementation in reducing the recovery time of erythropoiesis in blood donors postdonation as earlier reported in some studies. This has already been formulated into guidelines for blood bank services in developed climes.[14],[15] Unfortunately, this is yet to be routine for blood donors in blood transfusion services in Nigeria and possibly in most transfusion services in the LMICs. Reasons for this may border on first, the cost of iron supplementation in most LMIC which is mostly out of pocket expenses,[16],[17],[18] second, poor structure of blood bank transfusion services, and third, lack of donor care and retention strategies.

Studies have reported wide variation in the prevalence of iron-deficiency anemia among blood donors, ranging from 1% to 72.1%.[9],[19],[20] This study reported a prevalence rate of 13%, which is comparable to rates reported by an Indian study and a 10-year systematic review of iron deficiency in blood donors done by a Columbian group.[21],[22] However, the study prevalence rate is low compared to prevalence rates of 20% and 24% reported from studies done in Port Harcourt and Sokoto both in Nigeria, respectively.[9],[19] The reasons for this could be attributed to sex distribution of the donors, donation history, and type of blood donors. For the present study, the majority of the participants were male (86%) and donated blood regularly (donated blood at least twice in the previous 12 months). We equally observed that this prevalence was reduced to 1% after 6 weeks of daily iron supplementation using Ranferon. This is in keeping with a previous works where it was noted that iron supplementation is needed to prevent iron-deficiency anemia in blood donors.[23],[24]

Compliance to oral iron therapy is usually compromised by gastrointestinal tract (GIT) side effects. Most of participants tolerated the iron supplementation using Ranferon. There was only a single report of GIT side effects, which consisted of abdominal discomfort, diarrhea, and vomiting. This differs from high reports of GIT side effects from Smith et al. and Pastore et al.[25],[26]

Using the modified Morisot scale, most of our participants were motivated (88%) and knowledgeable (73%) on the benefits of adhering to iron supplementation as most participants (93%) adhered to the dose of iron prescribed, while 73% never missed any dosage. This is in keeping with 92.5% adherence noted by Kiss et al.[5] and is also similar to a study carried out by Bryant et al. in 2012.[27]

Limitation of the study

Participants' compliance to study protocols was based on information they volunteered. There may have been recall bias for adherence and compliance to the study protocols.

   Conclusion Top

Six weeks daily iron supplements using Ranferon is well tolerated with minimal GIT side effects and increased levels and percent recovery of red cell variables, red cell indices, and iron study variables. This study supports the practice of iron supplementation among blood donors especially in LMIC as deferrals due to low Hb will be greatly reduced.


Evidence from this study shows and supports that there are benefits from daily iron supplement post blood transfusion. We recommend the routine use of iron supplement as it does reduce the recovery time of red cell parameters and indices and may safely increase the frequency of blood donation from every 12 weeks to 6–8 weeks. Use of Ranferon as the source of elemental iron show good side effect profile and reduced incidence of reported gastrointestinal discomfort elemental iron is known for. National multicentered large-sample-sized studies are recommended to explore and generate more data on iron supplementation in regular blood donation across cultures and geographical locations in Nigeria.


We thank the staff of UNTH Blood Bank for their assistance in carrying out this study. We also thank Sun Pharmaceuticals Industries Ltd., for providing the funds for this study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

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Mittal R, Marwaha N, Basu S, Mohan H, Ravi Kumar A. Evaluation of iron stores in blood donors by serum ferritin. Indian J Med Res 2006;124:641-6.  Back to cited text no. 2
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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