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Journal of Rawalpindi Medical College (JRMC); 2014;18(1):139-141

Original Article

Latent Deficiency and Anaemia in Hypoferritinemic Patients

Masooma Raza*,Samina T.Amanat **, Tariq Hussain**, Huma Abdul Shakoor*, Muhammad Asghar*. *Department of Pathology, Pakistan Atomic Energy Commission General Hospital, Islamabad;** Department of Medicine, Pakistan Atomic Energy Commission General Hospital, Islamabad

Abstract of . levels must be assayed for assessing body iron stores. Background : To find out the frequency of iron Hypoferritinemia, Iron deficiency deficiency anaemia (IDA) and Key Words: (LID) amongst hypoferritinemic individuals anemia, Latent iron deficiency, Haemoglobin, Iron

Methods : In this descriptive study individuals (n=1821) who were referred for serum ferritin Introduction estimation, for a period of one year were included. Iron deficiency anemia (IDA) is widely prevalent Ferritin levels were assayed by enhanced in Pakistan. IDA is preceded by a stage of latent iron chemiluminisence method. Haemoglibin levels were deficiency (LID) where serum ferritin is reduced but also estimated in all these subjects.Those and red indices are normal. Iron hypoferritinemic subjects were excluded from the depletion may be three times as common as iron study whose haemoglobin levels were not performed deficiency anaemia (IDA), which has a prevalence of 2- on the same day as serum ferritin assay, with raised 5% of adult men and postmenopausal women in the C-reactive proteins or had leukocytosis. Male developed world. Iron depletion is more common in patients having haemoglobin <13g/dl and female the developing world like Pakistan especially amongst patients with haemoglobin <12 g/dl were considered women because of , as a result, some anaemic. Children from 2-12 years were included in workers consider haemoglobin level of 10-11 g/dl as this study and children having haemoglobin below normal. 1,2 10 g/dl were considered anaemic. Patients with Iron depletion is a reduced content of total body normal haemoglobin, but with low serum ferritin iron. Iron deficiency anaemia(IDA) occurs when the were considered as suffering from latent iron iron deficiency is sufficient to reduce erythropoiesis deficiency anaemia Normal range of serum ferritin and therefore the haemoglobin (Hb) level falls. for adult male subjects was 12-300 ng/ml, for adult However, problems related to iron depletion can female subjects is 10-150 ng/ml and for children develop before this stage diagnosed by serum ferritin of 17-464 ng/ml was considered hypoferritinemia. This stage is occasionally detected normal. by a routine check of the serum ferritin or Results: Total number 1821 samples of serum saturation. Iron deficiency, with or without ferritin were assayed by enhanced concomitant anemia also has serious implications and chemiluminesence method out of which 458 (25.15 need to be treated. In children this leads to impairment %) number of patients had low serum ferritin. of growth and intellectual development. 981(53.87%) subjects had normal ferritin levels and Iron is the most abundant element on earth, with 382(20.97%) patients had high ferritin levels. In potential of high toxicity to living cells. Therefore, hypoferritinemic patients gender distribution complex regulatory mechanisms are present in human included total of adult males 88 (19.21%) adult to insure adequate intestinal absorption, females 222 (48.47 %) and 148 (32.31 %) children transportation, utilization, and elimination. Iron greater than 2 years.Subjects with low serum ferritin balance is regulated by absorption of iron rather than were divided into two groups latent iron deficient by excretion, because humans cannot actively excrete group and iron deficiency anaemic patients. Latent iron. Iron is absorbed from the small intestine.Iron is iron deficiency (LID) was seen in 19.43% . Mean lost from the body through sloughed skin cells and serum ferritin was low in IDA as compared to LID . sloughed enterocytes from the gut, and through any Conclusions: Latent iron deficiency may be form of blood loss. Males contain about 4,000 mg of missed if hemoglobin levels are taken as sole marker iron, of which 2,500 mg is within erythrocytes; 1,000

139 Journal of Rawalpindi Medical College (JRMC); 2014;18(1):139-141 mg is stored in splenic and hepatic macrophages, and period of one year (June 2012 to June 2013) were the rest is distributed in various proteins such as included. Ferritin levels were assayed by enhanced myoglobin, or other ferroproteins. About chemiluminisence method. Haemoglobin levels were 1–2 mg of iron is lost every day, through skin and also estimated in all these subjects.Those enteric desquamation and minor blood losses. This hypoferritinemic subjects were excluded from the loss is balanced by intestinal absorption. Therefore, study whose haemoglobin levels were not performed iron recycling accounts for most of the iron on the same day as serum ferritin assay, with raised C- homeostasis in human. reactive proteins or had leukocytosis. Male patients For detection of body iron status several tests are having haemoglobin <13g/dl and female patients with available. Nowadays bone marrow examination has haemoglobin <12 g/dl are considered anaemic. been replaced by the measurement of blood ferritin. Children from 2-12 years were included in this study Other tests, like measurements of transferrin (Tf), of and children having haemoglobin below 10 g/dl soluble transferrin receptor (sTfr) or of , are considered anaemic. Patients with normal also available reflecting dynamics of iron metabolism. haemoglobin, but with low serum ferritin were Hepcidin, is a 25 amino acid peptide hormone, mainly considered as suffering from latent iron deficiency produced by hepatocytes, plays very important role in anaemia .Normal range of serum ferritin for adult iron metabolism. Many mechanisms involved in the male subjects is 12-300 ng/ml, for adult female regulation of hepcidin may therefore regulate subjects is 10-150 ng/ml and for children, serum availability of iron to erythropoiesis by adaptation of ferritin of 17-464 ng/ml is considered normal. iron absorption and recirculation. Erythrocyte precursors take up iron through transferrin Results receptors,Tfr. Thus, the Tf cycle is dependent on the Total 1821 samples of serum ferritin were assayed by Tf-Tfr complex trafficking, involving internalization of enhanced chemiluminesence method out of which 458 the complex within endosome, followed by iron (25.15 %) number of patients had low serum ferritin. release upon acidification of the endosome and 981(53.87%) subjects had normal ferritin levels and recycling of the Tf-Tfr complex to the cell surface 382(20.97%) patients had high ferritin levels. where, Tf dissociates from Tfr, and is used to repeat the iron cycle. Ferrous is reduced to ferric by Table 1: Hypoferritinemia- Subjects distribution ferrireductase , as only ferric iron is transported to the Latent Iron Iron Total no of cytoplasm or to mitochondria. Due to its toxicity, iron deficiency(LID) Deficiency patients within the cytoplasm is associated with proteins such Anemia(IDA) as poly(RC)-binding protein 1 , functioning as Males 13(2.83%) 75(16.37%) 88(19.21%) Females 21(4.58%) 201(43.88%) 222(48.47%) cytosolic iron chaperone in the delivery of iron to Children 55(12%) 93(20.30%) 148(32.31%) ferritin. Within the ferritin molecule, iron is stored in Total 89(19.43%) 369(80.56%) 458(100%) the ferric form associated with hydroxide and phosphate anions. Each ferritin molecule can sequester Table 2: Comparison of mean levels of Hemoglobin up to approximately 4,500 iron atoms. Ferritin also has and Ferritin in hypoferritinemic patients (n= 458) enzymatic properties, converting ferric to ferrous iron, IDA (n=201) LID (n=21) as iron is internalized and sequestered in the ferritin Adult Hb(g/dl) 8.79±1.57 12.54±0.71 core. 3 females Ferritin (ng/ml) 4.62±1.1 5.84±2.93 (n=222) IDA is an end stage of negative iron balance. It is Adult Hb(g/dl) 9.20±2.35 13.67±0.93 preceded by a stage of latent iron deficiency (ID) males Ferritin (ng/ml) 6.82±3.88 10.59±3.56 where serum ferritin is below 15.0 ng/ml with normal (n=88) Hb level. 4 It would be interesting to see the prevalence Children Hb(g/dl) 7.89±1.52 11.37±1.08 of latent ID in addition to IDA. Mild anemia is (n=148) Ferritin (ng/ml) 6.09±3.69 8.62±4.60 asymptomatic or cause non-specific symptoms. It would be of interest to find out latent iron deficiency In hypoferritinemic patients, gender distribution and this treatable should be treated simply by included total of adult males 88 (19.21%) adult females taking oral iron supplements. 222 (48.47 %) and 148 (32.31 %) children older than 2 years.Subjects with low serum ferritin were divided Patients and Methods into two groups latent iron deficient group and iron In this descriptive study individuals (n=1821) who deficiency anaemic patients. Latent iron deficiency were referred for serum ferritin estimation, for a

140 Journal of Rawalpindi Medical College (JRMC); 2014;18(1):139-141

(LID) was seen in 19.43% (Table 1). Mean serum hypoferritinemic individuals noted higher frequency ferritin was low in IDA as compared to LID (Table 2). of anemia in females, (48.47 %). This result is comparable to other studies.13-16 Discussion Iron is an important micronutrient required for Conclusion multiple functions in body.5- 8 Iron deficiency is a Latent iron deficiency has clinical implications and it major health issue in developing countries like may be missed if hemoglobin levels are taken as sole Pakistan where its rates have been reported to vary marker of anemia. Ferritin levels must be assayed for between 30-69%.8 Approximately 39% of adolescents, assessing body iron stores. 30% boys and 54% girls, 47% of the children, 30% of the adult females, 40-50 % of preschool and primary References school children, and 69% children <2 years, were 1. Ilyas, M.M.Q, Shujaat A.K, Kalsoom F, Ghulammmm M, reported to be affected by IDA.9 Two different Saira A. Prevalence of iron deficiency in adult population: A prevalence studies, in semi urban areas of Peshawar case study from Khyber Pakhtunkhwa, Pakistan. IJPS, 7, 1874-77. found 69% prevalence (Hb <11 g/dl) of anaemia in 2. Qureshi AF, Hashmi HH, Akhtar DS. Adolescent reproductive children under two years and in urban slums of health-A Manual for family physicians, Karachi: JCPSP Karachi detected 61 %( Hb <11 g/dl) of anaemia in Pakistan; 1999. children aged 6- 60 months.10, 11 A recent study at 3. Abramowski SW, Waeber G, Gassner C,Buser A. Physiology of Iron Metabolism. Transfus Med Hemother 2014;41:1213- 12 Abbottabad detected 68 % anaemia prevalence. 16 No single test can describe iron status 4. Ochmann O, Hardegger K, Frey B.M. Iron balance in young accurately, so there are a number of markers that, blood donors: is the latent iron deficiency syndrom (LIDS universal? Stiftung Zürcher Blutspendedienst SRK, CH - collectively, describe an individual’s iron “status,” 8001 Zürich. including serum (circulating) iron, 5. Akarsu S, Kilic M, Yilmaz E, Aydin M, Taskin E. Frequency count, hemoglobin, hematocrit, total iron binding of Hypoferritinemia, Iron Deficiency and Iron Deficiency capacity, and serum ferritin. Serum ferritin is a Anemia in Outpatients. Acta Haematol 2006;116:46–50. 6. Rao R, Georgieff MK. Iron in fetal and neonatal nutrition. surrogate marker of stored iron. Limitation of ferritin Semin Fetal Neonatal Med 2007 ; 12(1):54-63. is that as it is a acute phase protein, so high serum 7. Allen L. Anemia and iron deficiency: effects on pregnancy ferritin is present with . When serum outcome. Am J Clin Nutr. 2000;71( 5):S1280 –84 ferritin is low, without low haemoglobin, it is called 8. Allen L. Pregnancy and iron deficiency: unresolved issues. Nutr Rev. 1997;55:91–101 latent iron deficiency, whereas when there is also low 9. Akhtar S, Ahmed A, Ahmad A, Ali Z, Riaz M, Ismail T. Iron hemoglobin, it is iron deficiency anemia. In the status of the Pakistani population-current issues and population where iron deficiency is common it is strategies. Asia Pac J Clin Nutr. 2013;3:340-47. 10. Paracha PI, Hameed A, Simon J, Jamil A, Nawaz G. important to identify the patients with latent iron Prevalence of anaemia in semi urban areas of Peshawar, deficiency, as these patients also need treatment Pakistan. A Challenge for health professionals and Policy because iron is also required by other body tissues and makers. J Pak Med Assoc. 1997; 47(2): 49-53. .Moreover, timely treatment will prevent the 11. Molla A, Khurshid M, Molla AM. Prevalence of Iron deficiency anaemia in Children of the urban slums of development of anaemia. In patients with slow Karachi. J.Pak Med Assoc.1992 May; 42 (5): 118-21. developing anaemia have usually very mild symptoms 12. Idris M and Rehman AU. Iron deficiency anaemia in and they do not seek medical advice, as shown in an moderate to severely anemic patients. J Ayub Med Coll Indian study where IDA was detected in 20.3% of Abbottabad. 2005; 17(3): 45-47. 13. Mehta BC. Iron deficiency amongst nursing students. Indian apparently healthy females aged 18-23 years.13 J Med Sci 2004; 58:389-93 Another study conducted in Iran, the prevalence rates 14. Shams S, Asheri H, Kianmehr A, Ziaee V. The prevalence of of ID and IDA in female university students aged 18– iron deficiency anaemia in female medical students in 14 Tehran. Singapore Med J 2010; 51(2) : 116-19 25 years were 40.9% and 3.8%, respectively. 15. Cetin I, Bulut Y, Yildirim B, Ozturk B, Yenisehirli G .The In our study, latent iron deficiency was found investigation of some hematological values and anemia amongst 19.43% of hypoferritinemic people while prevalence in adult population of Tokat province. 80.56% had iron deficiency anemia. Thus latent iron International Journal of and Oncology.2009;3:166-74. deficiency accounted for significant proportion of 16. 16. Dallman PR, Yip R, Johnson C. Prevalence and causes of hypoferritinemic individuals. Our study of 458 anemia in the United States. Am J Clin Nutr.1984;39:437-45

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