HEMATOLOGY SECTION - ORIGINAL ARTICLE
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
Richa Goyal1, Reena Das1, Pradeep Bambery2, Gurjeewan Garewal1,
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
Department of Hematology, PGIMER, Chandigarh - 160 012
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.
|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;51:102-104
|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 2023 Feb 1 ];51:102-104
Available from: https://www.ijpmonline.org/text.asp?2008/51/1/102/40417
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. ,, Iron therapy in RA patients without iron deficiency may aggravate arthritic symptoms as well as fail to manage anemia.  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. 
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.  In IDA, there is upregulation of synthesis of transferrin receptor so that cells can compete for iron more efficiently.  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.  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. , 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.  We attempted to determine the prevalence of ACD and ACD with coexistent IDA in RA patients using sTfR-F index.
Materials and Methods
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 1.5 were classified as ACD with coexistent IDA.  Data are presented as the mean and range and the comparison of the data was carried out using the Student's t-test.
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 2.9 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 p , 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. 
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. ,, 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.
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 2.9 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.
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