LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 5322
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size


 
HEMATOLOGY SECTION - ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 1  |  Page : 102-104
Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India


1 Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012, India
2 Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012, India

Click here for correspondence address and email
 

   Abstract 

Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value <1.5 were classified as pure ACD and patients with sTfR-F index value >1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.

Keywords: Anemia of chronic disorder, iron deficiency anemia, rheumatoid arthritis, TfR - F index

How to cite this article:
Goyal R, Das R, Bambery P, Garewal G. Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India. Indian J Pathol Microbiol 2008;51:102-4

How to cite this URL:
Goyal R, Das R, Bambery P, Garewal G. Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India. Indian J Pathol Microbiol [serial online] 2008 [cited 2020 Oct 21];51:102-4. Available from: https://www.ijpmonline.org/text.asp?2008/51/1/102/40417



   Introduction Top


Anemia is a cause of morbidity in patients with rheumatoid arthritis (RA), which is a prototypic disease of anemia of chronic disorder (ACD), although other causes of anemia such as iron deficiency anemia (IDA) can coexist. It is important to identify cases with concomitant IDA since patients will benefit symptomatically by therapy with iron. According to various studies conducted in developed countries, iron deficiency is found in 30-60% of RA patients. [1],[2],[3] Iron therapy in RA patients without iron deficiency may aggravate arthritic symptoms as well as fail to manage anemia. [4] In a developing country such as India, the prevalence of iron deficiency in the general population is high.

The definitive method to distinguish between IDA and ACD is the assessment of stainable iron in bone marrow. Bone marrow examination is an invasive procedure, causes discomfort to the patient and cannot be repeated often. Therefore, there is a demand for noninvasive methods to determine the presence of concomitant IDA. Red cell indices and iron parameters such as total iron binding capacity (TIBC) show considerable overlap. In general, IDA is associated with a serum ferritin value below 20 µg/L whereas a serum level above 100 µg/L excludes iron deficiency in majority of cases. Serum ferritin being an acute phase reactant increases nonspecifically in inflammatory conditions despite the presence of iron deficient stores and values between 20 and 100 µg/L fall in the diagnostic gray zone. [5]

Serum transferrin receptor (sTfR) is the truncated form of cell surface transferrin receptor, which causes the internalization of iron in erythroid cells. Serum transferrin receptor is increased in IDA as compared to ACD and has a role in classifying the type of anemia. [6] In IDA, there is upregulation of synthesis of transferrin receptor so that cells can compete for iron more efficiently. [7] In ACD, an increase in erythroblast surface TfR efficiency for iron uptake compensates for low plasma levels, resulting in normal sTfR. However, the erythroblasts respond to any additional worsening of iron supply caused by absent reticuloendothelial iron stores. This leads to increase of sTfR value in RA patients with concomitant iron deficiency. [8] Studies indicate that logarithmic transformation of the ferritin values and calculation of sTfR/log ferritin ratio (sTfR-F index) provides an outstanding indicator of iron depletion. [9],[10] The index takes advantage of the relationship between the two phenomena, i.e., an increase in TfR and a decrease in the ferritin concentration. Although both RA and IDA are common problems in India, there is paucity of data regarding the prevalence of ACD and ACD with coexistent IDA in RA patients. A study from India using sTfR showed 46% prevalence of concomitant iron deficiency in ACD patients. [11] We attempted to determine the prevalence of ACD and ACD with coexistent IDA in RA patients using sTfR-F index.


   Materials and Methods Top


Institutional ethical approval was taken to conduct the study. One hundred and ninety eight chronic rheumatoid arthritis patients meeting the American Rheumatology Association (ARA) criteria were studied prospectively. There were 179 females and 19 males (9.4:1) and mean age was 43.3 years (range: 16-75 years). At the time of investigation, none of the patients were suffering from any acute episode of rheumatism. Twenty-five documented IDA subjects without any other illness (serum ferritin value <5 µg/L) and 25 age- and sex-matched normal controls with no underlying disorder were also studied. Overnight fasting blood sample was taken in EDTA vial (2 ml) and in iron-free tube (6-8 ml). Complete hemogram including hemoglobin (Hb), packed red cell volume, red cell indices such as mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count and total leucocyte count, were carried out using Sysmex K-1000/SF 3000 electronic counters. Manual reticulocyte counts (%) were performed taking the average value of two experienced hematologists. Erythrocyte sedimentation rate (ESR) was carried out using the Wintrobe tube. Patients with Hb < 130 g/l (males) and <120 g/l (females) were investigated for: serum iron, total iron binding capacity (TIBC) (measured with standard colorimetric assay and percent transferrin saturation was calculated), serum ferritin (Orgentec's ELISA kit) and serum transferrin receptor (R and D system's ELISA kit, the values in nmol/L were converted to mg/L). The ratio of sTfR to log ferritin (sTfR-F index) was determined.

We used sTfR-F index cut off levels to decide concomitant iron deficiency anemia in chronic RA patients. Patients with sTfR-F index value <1.5 were classified as pure ACD and patients with sTfR-F index value >1.5 were classified as ACD with coexistent IDA. [10] Data are presented as the mean and range and the comparison of the data was carried out using the Student's t-test.


   Results Top


The hematological parameters and results of the iron studies of our control cases 25 each of isolated iron deficiency anemia and normal controls are given in [Table - 1]. Higher values of sTfR were found in IDA control cases as compared to normal controls. The comparison of data of control cases revealed that sTfR value <2.2 mg/L excludes while the value >2.9 mg/L confirms IDA. Serum TfR between 2.2 and 2.9 mg/L is the overlap range and therefore should not be interpreted independently if the value falls in this range. In the normal control group, sTfR-F index was found to be 0.16-1.8, while that in IDA controls, it was found to be 3.1-38.3. Therefore, there was no overlap of values encountered. Of 198 RA subjects, 100 (50.5%) were found to be anemic. Mean corpuscular volume (MCV) in all of the anemic patients was less than 100 fl, excluding macrocytic anemia. The degree of anemia was mild (Hb > 90 g/L) in 76%, moderate in 22% and severe (Hb < 70 g/L) in 2% patients. None of these cases had reticulocytosis. On analyzing the individual hematological and iron parameters, there was considerable overlap to classify patients into either ACD or ACD with IDA. However, using the sTfR-F index, the anemic RA patients could be clearly divided into two groups of 20 patients with pure ACD and 80 patients with ACD and coexistent IDA. The parameters that showed a significant difference ( p < 0.05) between pure ACD and ACD with coexistent IDA included Hb, MCV, MCH, MCHC, RDW and TIBC [Table - 2].


   Discussion Top


The importance of accurate assessment of iron status in chronically ill patients is clearly evident in two different situations. It is necessary to identify patients with iron deficiency anemia (IDA), even in the presence of complicating factors, since the treatment of these patients with iron supplementation is effective and straightforward. However, to optimize the use of supplemental iron in treatment of anemic conditions other than IDA, it is necessary to identify patients with functional iron deficiency, i.e., anemia of chronic disorder (ACD). No single parameter was recommended for the identification of iron deficiency in RA patients; however, recently serum transferrin receptor ferritin index (sTfR-F index) has been found to be a useful measure. [9],[10] Punnonen et al. evaluated a variety of possibilities of combining the sTfR and ferritin parameters; the results suggest that the logarithmic transformation of the ferritin values and calculation of sTfR/log ferritin ratio (the sTfR-F index) provides an outstanding indicator of iron depletion. They found the sensitivity and specificity of sTfR-F index to be 94% and 100%, respectively, at a cut off level of 1.5 on comparing ACD from coexistent ACD and IDA. [10]

The prevalence of anemia in RA patients reported in western studies varies from 16 to 65%, and approximately, 30 to 60% of these suffer from iron deficiency. [2],[3],[4] In our study, the prevalence of anemia in RA patients was 50.5%. We found that 80% of the patients with RA had ACD with concomitant IDA. The higher percentage of IDA in this study may be due to higher prevalence of iron deficiency in general population. A comparison of the prevalence of IDA in chronic rheumatic diseases in various studies has been shown in [Table - 3]. Using sTfR-F index we could classify our patients into ACD with coexistent IDA (80%) and pure ACD (20%). The presence of concomitant ACD shows that therapeutic erythropoietin may be indicated in addition to iron preparations if anemia does not respond to only iron therapy. In our study, a number of parameters (Hb, MCV, MCH, MCHC, RDW and TIBC) showed a significant difference between ACD and ACD with coexistent IDA patients. However, no individual parameter can be recommended to distinguish between the two groups.[14]


   Conclusions Top


Anemia is frequently encountered in patients with rheumatoid arthritis. Higher values of sTfR were found in IDA control cases as compared to normal controls. The comparison of data of control cases revealed that sTfR value <2.2 mg/L excludes IDA while the value >2.9 mg/L confirms IDA. Serum TfR between 2.2 and 2.9 mg/L is the overlap range and therefore should not be interpreted independently if the value falls in this range. Our study shows that sTfR-F index can clearly distinguish between IDA control cases and normal subjects since there is no overlap in the range of sTfR-F index in normal control cases and IDA control cases. In patients with RA, ACD with iron deficiency anemia is frequent (80%). In our country, due to limited resources available, the relatively expensive test of serum transferrin receptor cannot be recommended.

 
   References Top

1.Kurer SB, Seifert B, Michel B, Ruegg R, Fehr J. Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia. Br J Haematol 1995;91:820-6.  Back to cited text no. 1    
2.Baer AN, Dessypris EN, Krantz SB. The pathogenesis of anemia in rheumatoid arthritis: A clinical and laboratory analysis. Semin Arthritis Rheum 1990;19:209-23.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Doube A, Davis M, Smith JG, Maddison PJ, Collins AJ. Structured approach to the investigation of anemia in patients with rheumatoid arthritis. Ann Rheum Dis 1992;51:469-72.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Blake DR, Lunec J, Ahern M, Ring EF, Bradfield J, Gutteridge JM. Effects of intravenous iron dextran on rheumatoid arthritis. Ann Rheum Dis 1985;44:183-8.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. Lab Clin Med 1992;19:385-90.  Back to cited text no. 5    
6.Shih YJ, Baynes RD, Hudson BG, Cook JD. Characterisation and quantification of the circulating forms in serum transferrin receptor using domain specific antibodies. Blood 1993;81:234-8.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Cook JD. The measurement of serum transferrin receptor. Am J Med Sci 1999;318:269-76.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Fitzsimons EJ, Houston T, Munro R, Sturrock RD, Speekenbrink AB, Brock JH. Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia of rheumatoid arthritis. Arthritis Rheum 2002;47:166-71.  Back to cited text no. 8  [PUBMED]  
9.Suominen P, Mottonen T, Rajamaki A, Irjala K. Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum 2000;43:1016-20.  Back to cited text no. 9    
10.Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron- deficiency. Blood 1997;89:1052-9.  Back to cited text no. 10    
11.Das Gupta A, Abbi A. High serum transferrin receptor level in anemia of chronic disorders indicate coexistent iron deficiency. Am J Hematol 2003;72:158-61.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Pettersson T, Kivivuori SM, Siimes MA. Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases? Br J Rheumatol 1994;33:740-4.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Nielsen OJ, Andersen LS, Hansen NE, Hansen TM. Serum transferrin receptor levels in anaemic patients with rheumatoid arthritis. Scand J Clin Lab Invest 1994;54:75-82.  Back to cited text no. 13  [PUBMED]  
14.Zoli A, Altomonte L, Mirone L, Magaro M, Ricerca BM, Storti S, et al . Serum transferrin receptors in rheumatoid arthritis. Ann Rheum Dis 1994;53:699-701.  Back to cited text no. 14    

Top
Correspondence Address:
Reena Das
Department of Hematology, PGIMER, Chandigarh - 160 012
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.40417

Rights and Permissions



 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]

This article has been cited by
1 Lower Plasma Soluble Transferrin Receptor Range in Healthy Indian Pediatric Cohort as Compared to Asian and Western Data
P. Bhatia,D. Siyaram,D. Deepshikha,R. Marathe,D. Dayal
Indian Journal of Hematology and Blood Transfusion. 2017; 33(3): 405
[Pubmed] | [DOI]
2 Hematological Practice in India
Reena Das,Jasmina Ahluwalia,Man Updesh Singh Sachdeva
Hematology/Oncology Clinics of North America. 2016; 30(2): 433
[Pubmed] | [DOI]
3 Using Soluble Transferrin Receptor and Taking Inflammation into Account When Defining Serum Ferritin Cutoffs Improved the Diagnosis of Iron Deficiency in a Group of Canadian Preschool Inuit Children from Nunavik
Huguette Turgeon O’Brien,Rosanne Blanchet,Doris Gagné,Julie Lauzičre,Carole Vézina
Anemia. 2016; 2016: 1
[Pubmed] | [DOI]
4 Anemia in Inflammatory Bowel Disease: An Under-Estimated Problem?
Gerhard Rogler,Stephan Vavricka
Frontiers in Medicine. 2015; 1
[Pubmed] | [DOI]
5 Serum Transferrin Receptors in Children with Hypochromic Microcytic Anaemia
Maria Aslam,Shahida Mohsin,Huma Amin,Shabbir Hussain,Nisar Ahmed,Ayesha Bhalli
Open Journal of Pathology. 2014; 04(02): 41
[Pubmed] | [DOI]
6 Association of aggressive periodontitis with reduced erythrocyte counts and reduced hemoglobin levels
P. S. Anand,D. K. Sagar,S. Ashok,K. P. Kamath
Journal of Periodontal Research. 2013; : n/a
[Pubmed] | [DOI]
7 Disordered Iron Homeostasis in Chronic Heart Failure: Prevalence, Predictors, and Relation to Anemia, Exercise Capacity, and Survival
M.D. Cheitlin
Yearbook of Cardiology. 2012; 2012: 349
[Pubmed] | [DOI]
8 Disordered Iron Homeostasis in Chronic Heart Failure
Darlington O. Okonko, Amit K.J. Mandal, Constantinos G. Missouris, Philip A. Poole-Wilson
Journal of the American College of Cardiology. 2011; 58(12): 1241
[VIEW] | [DOI]
9 Serum Hepcidin: A Direct Link Between Anemia of Inflammation and Coronary Artery Atherosclerosis in Patients with Rheumatoid Arthritis
MANAL ALY ABDEL-KHALEK,AMAL MOHAMAD EL-BARBARY,SALWA ABDEL-MONEIM ESSA,ABEER SAEED GHOBASHI
The Journal of Rheumatology. 2011; 38(10): 2153
[Pubmed] | [DOI]
10 Evaluation of serum transferrin receptor and sTfR ferritin indices in diagnosing and differentiating iron deficiency anemia from anemia of chronic disease
Sonal Jain, Priya Malhan, Shilpa Jain, Shashi Narayan, Jagdish Chandra, Sunita Sharma
The Indian Journal of Pediatrics. 2010; 77(2): 179-183
[Pubmed] | [DOI]
11 Serum transferrin receptor concentrations in diagnosing and differentiating iron deficiency anemia from anemia of chronic diseases in children
Fathy, M.A., Fathy, H.A., Alkady, M.M., Khalifa, N.M., El-Menshawy, A.A.
Journal of Applied Sciences Research. 2010; 6(8): 3669-3676
[Pubmed]
12 Serum transferrin receptor concentrations in diagnosing and differentiating iron deficiency anemia from anemia of chronic diseases in children
Fathy, M.A., Fathy, H.A., Alkady, M.M., Khalifa, N.M., El-Menshawy, A.A.
Australian Journal of Basic and Applied Sciences. 2010; 4(8): 3669-3676
[Pubmed]
13 Iron deficiency anemia: diagnosis and management
Susan F Clark
Current Opinion in Gastroenterology. 2009; 25(2): 122
[Pubmed] | [DOI]
14 Iron deficiency anemia: Diagnosis and management
Clark, S.F.
Current Opinion in Gastroenterology. 2009; 25(2): 122-128
[Pubmed]



 

Top
 
  Search
 
  
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Introduction
    Materials and Me...
    Results
    Discussion
    Conclusions
    References
    Article Tables

 Article Access Statistics
    Viewed8439    
    Printed171    
    Emailed6    
    PDF Downloaded599    
    Comments [Add]    
    Cited by others 14    

Recommend this journal