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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 1  |  Page : 22-25

Hemoglobin and serum ferritin concentration in anemic and nonanemic human immunodeficiency virus females in India


1 Department of Biochemistry, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India
2 Department of Obstetrics and Gynecology, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India
3 Department of Medicine, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India

Date of Submission19-Oct-2016
Date of Acceptance20-Dec-2017
Date of Web Publication30-Apr-2018

Correspondence Address:
Dr. Simmi Kharb
#1396, Sector-1, Rohtak, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhrr.jhrr_90_16

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  Abstract 

Aim: This study was planned to assess hemoglobin (Hb) and serum ferritin in anemic and nonanemic HIV females. Materials and Methods: The present prospective study was conducted during 2012–2013 in the department of biochemistry in collaboration with department of medicine (HIV clinic). In 200 seropositive females (age: 18–50 years) attending antiretroviral therapy clinic after routine gynecological and hematological investigations, CD4 count, serum iron, and ferritin were analyzed by chemiluminescence. Results were calculated by SPSS version 17. Student's t-test and regression analysis were done. Results: Hb showed a positive correlation with serum iron and ferritin and was statistically significant. Anemia occurs most commonly in these patients and indicates increased risk of mortality. Serum ferritin was correlated to CD4 cell counts indicating that level of HIV disease progression and viral load. Finding of high serum ferritin with high CD4 in the present study support to the role of inflammation in increased serum ferritin levels and high iron stores in HIV may have adverse events and effects. Conclusion: High ferritin levels in HIV patients suggest that redistribution of iron and decreased activity of erythropoietic cells is mainly responsible for anemia. Serum ferritin levels need to be evaluated carefully in HIV patients with advanced disease. Iron overload and adverse HIV related outcomes due to high iron exposure can be prevented by screening the iron status and stores in anemic HIV women. Also there is need of other effective strategies of locating other causes of anemia that should be adopted.

Keywords: Anemia and antiretroviral therapy clinic, ferritin, human immunodeficiency virus, iron, seropositive women


How to cite this article:
Kharb S, Lallar M, Ghalaut P S, Bala J, Kumawat M, Nanda S. Hemoglobin and serum ferritin concentration in anemic and nonanemic human immunodeficiency virus females in India. J Health Res Rev 2018;5:22-5

How to cite this URL:
Kharb S, Lallar M, Ghalaut P S, Bala J, Kumawat M, Nanda S. Hemoglobin and serum ferritin concentration in anemic and nonanemic human immunodeficiency virus females in India. J Health Res Rev [serial online] 2018 [cited 2018 May 21];5:22-5. Available from: http://www.jhrr.org/text.asp?2018/5/1/22/231535


  Introduction Top


In human immunodeficiency virus (HIV)-infected patients, anemia is a common clinical finding and is mainly responsible for progression in disease, poor survival, and increased mortality risks.[1],[2],[3],[4] There are many reasons responsible for anemia in these patients such as iron deficiency and inflammation-induced iron maldistribution.[3],[5]

Inflammation is mainly responsible in HIV patients for diversion of iron from circulation into the reticuloendothelial system and for tissue storage which is mainly responsible for increased incidence of opportunistic infections and progression in disease.[6],[7],[8],[9],[10] HIV infection may contribute to aberrant immune activation that exacerbates other etiologies of anemia. Molecular mimicry between erythropoietin (EPO) and the HIV-1 p17 protein can lead to circulating autoantibodies against endogenous EPO in some HIV patients, blunting the normal physiologic cytokine response to anemia.[11]

Serum ferritin levels rise in infections and inflammatory processes. Serum ferritin levels represent iron status of the body. In the absence of any infectious state, decreased serum ferritin concentration is an indicator of decreased iron stores.[12] In acute phase response, iron redistribution occurs in the liver and mononuclear phagocytic system. Cytokines such as tumor necrosis factor-alpha and interleukin-1 (IL-1) and IL-6 causes decrease in serum iron concentration within 3–6 h, and This study has shown that in vitro cytokine increases ferritin production. IL-6 may play significant role in potentiating anemia of inflammation through its role in regulating hepcidin, critical regulator of iron stores, and iron-limited erythropoiesis and has been linked with anemia of inflammation.[13]

Decreased ferritin levels act as protective mechanism in infectious disease by limiting availability of iron for the growth of pathogenic microorganism and also by decreasing the pro-oxidant property of iron which is responsible for tissue damage in inflammation. In inflammation, lactoferrin acts in hypoferremic-hyperferritinemic response and decreases serum iron levels by removing iron from transferrin and increasing ferritin concentration.[14]

There are controversies regarding ferritin status in HIV patients. Some studies had reported increased ferritin levels [10],[15],[16],[17] while others had observed decreased ferritin concentration.[18],[19]

Serum iron has two main roles in our body as iron store representative and as positive acute phase protein.[20] Serum ferritin levels were combined in past other marker of inflammation such as erythrocyte sedimentation rate (ESR) or C-reactive protein to assess severity of disease. Witte et al.[21] assessed serum ferritin and ESR in anemic individuals and observed that iron deficiency is present in approximately every patients with infectious anemia. The WHO reported that one or two acute phase proteins can be used collectively to accurately assess ferritin status in infectious diseases.[22]

It is not clear what proportion of anemia is attributable to iron deficiency and to what extent body iron store affect HIV disease progression. There is paucity of studies on iron status in HIV-infected women. This study was planned to correlate hemoglobin (Hb) with ferritin status in HIV women with and without anemia.


  Materials and Methods Top


Two hundred seropositive females (age: 18–50 years) attending antiretroviral therapy (ART) clinic of Medicine Department in collaboration with Department of Biochemistry and Obstetrics and Gynecology, Pt. B.D. Sharma PGIMS, Rohtak, were selected. This was a prospective study conducted during 2012–2013. Invasive or preinvasive cancers and pregnant females were excluded from the study. This study was approved by ethical committee of the institute in which study was carried out. Samples were collected after obtaining written consent from the patients.

Females with different gynecological disorders such as menstrual irregularities, vaginal infections, sexually transmitted disease, cervical dysplasia, and hematological abnormalities were included in the study after obtaining menstrual, medical treatment history and  Pap smear More Details. Venous samples were taken from all the cases under aseptic precautions and analyzed for hepatitis B surface antigen, STS(standard test for syphilis) status, Hb, peripheral blood film, serum iron, serum ferritin, and CD4 lymphocyte count.

Physical examination, including pelvic examination, was performed. CD4 lymphocyte count was done by flow cytometric technique. Cervicospinal Pap smear was taken from all cases and fixed in 95% of ethanol. Smears were examined after Papanicolaou staining. Serum iron and ferritin levels were estimated by chemiluminescence method. Data were calculated by (SPSS Inc. Released 2008. SPSS Statics for Windows, Version 17.0. Chicago : SPSS Inc.). Student's t-test and regression analysis were carried out.

The study protocol was approved by the Ethics Committee of PGIMS, Rohtak, on hemoglobin and serum ferritin concentration in anemic and nonanemic HIV females (PGIMS/19102016).


  Results Top


In the present study, anemia was a common presentation in HIV seropositive cases. Seven women had severe anemia (Hb levels <7 g%), 60 patients had moderate anemia (7–9.9 g%), and 90 had mild anemia (10–11.9 g%).

A significant positive correlation was found between Hb with serum iron and ferritin (r = 0.242, 0.118, respectively; P < 0.05, [Table 3]). Serum iron and ferritin levels are significantly higher in patients with Hb >12 g/dl or the nonanemics [Table 1] and [Table 2]. Only 3.5% of HIV-seropositive females had decreased serum iron levels while 90% had iron levels within the normal range. Six percent of patients had increased iron levels. Mean serum iron levels in anemic-seropositive patients were 88.48 ± 32.68 μg/dl and 98.23 ± 32.87 μg/dl in nonanemics which were not statistically significant (P > 0.05) using independent t-test. About 96.12% of anemic cases (n = 155) had iron deficiency (n = 149) since 96.12% of cases of anemia had iron deficiency indicating that there are other causes of anemia. Nearly 96.5% of women (n = 193) had iron deficiency (<150 g/L), 10.5% of women (n = 21) had ferritin (<12 g/L), and 25% of women (n = 50) had ferritin (<30 g/L). Serum ferritin <30 g/L was observed in 25% cases and they all (100%) had low iron levels.
Table 3: Correlation of Hb with haematological parameters using Pearson Correlation of Coefficient (r value)

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Table 1: Distribution of iron and ferritin according to hemoglobin levels (g%, mean±standard deviation)

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Table 2: Mean of serum iron as per hemoglobin status

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  Discussion Top


Anemia is a frequent complication of HIV disease that contributes to decreased quality of life and increased morbidity and mortality. Other studies had also reported results comparable to our study.[3],[23],[24],[25] The three major categories of anemia in HIV disease are anemia due to impaired red blood cell production, anemia due to increased red blood cell destruction, and anemia due to increased red blood cell loss. Although anemia of chronic illness is the most common type of anemia in HIV disease, other classifications of anemia may be encountered. Understanding the pathophysiology of anemia and laboratory tests that are frequently used to establish the differential diagnosis of anemia helps to ensure that HIV-infected individuals will receive appropriate treatment.

Anemia occurs widely among people living with HIV/AIDS. Anemia is difficult to diagnose because of the presence of various causative factors.[17] The proportion of anemia produced by iron deficiency may be underestimated in our study because the diagnosis of iron deficiency was based only on ferritin concentration. Ferritin is an acute phase protein, which is elevated in cases of infections.

Iron status is often evaluated by measuring serum ferritin levels. In the present study, high serum ferritin was seen in HIV patients, especially in patients with CD4 cell counts below 200 cells/mm 3.

Acute phase response seen in these patients is mainly responsible for iron redistribution and hence raised ferritin concentration. This is also contributing for raised iron levels in the liver, bone marrow, and other organs during the advanced stages of HIV.[26]

Inverse relation between ferritin and CD4 cell count can also occur by increased oxidative stress [27] due to decreased CD4 count.[28] This inverse relation between ferritin levels and CD4 cell comes to normal levels after ART because ART affects oxidative stress, plasma HIV-RNA, and/or inflammation.

Anemia, although usually mild, is more commonly seen in immune deficiency and mortality. Iron maldistribution is mainly responsible for anemia while the role of compromised erythropoiesis and HCV coinfection seems have little role.

Hb was not correlated with serum ferritin in anemic/nonanemic possibly because low Hb signals a more advanced form of iron deficiency than serum ferritin which reflects low iron stores. Furthermore, low Hb may be due to other nutritional or nonnutritional causes that are unrelated to iron status.

Serum ferritin was correlated to CD4 cell counts indicating that level of HIV disease progression and viral load. Finding of high serum ferritin with high CD4 in the present study and support to the role of inflammation in increase serum ferritin levels and high iron stores in HIV may have adverse events and effects.

Thus, iron overload and adverse HIV-related outcomes due to high iron exposure can be prevented by screening the iron status and stores in anemic HIV women, and other effective strategies of locating other causes of anemia should be adopted such as treatment of parasitic infections and other micronutrient supplementation in addition to ART.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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