Ann Rheum Dis: first published as 10.1136/ard.45.7.596 on 1 July 1986. Downloaded from
Annals of the Rheumatic Diseases, 1986; 45, 596-602
Serum ferritin as indicator of iron responsive anaemia in patients with rheumatoid arthritis
TROELS M0RK HANSEN' AND NIELS EBBE HANSEN2 From the 'Department ofRheumatology, Kong Christian X's Hospital 6300 Graasten, and the Department of Medicine, Division ofRheumatology, Hvidovre Hospital, 2650 Hvidovre, Denmark; and the 2Department of Medicine and Hematology, Gentofte Hospital, 2900 Hellerup, Denmark
SUMMARY In order to test the hypothesis that serum ferritin below 60 [ig/l is a good indicator of iron deficiency in patients with rheumatoid arthritis peroral iron was given to 67 patients with active rheumatoid arthritis over a three month period. A rise in haemoglobin concentration was taken as evidence of iron responsive anaemia. In anaemic patients serum ferritin below 60 [ig/l was a good indicator of iron responsive anaemia, with a predictive value of 83%. Although high plasma transferrin and low mean cell volume showed similar predictive values, more patients with iron deficiency anaemia could be diagnosed by serum ferritin measurements than by other conventional blood tests. In contrast, the predictive value of serum ferritin above 60 p.g/l was low (50%). The test was of no predictive value in non-anaemic patients. In patients with anaemia and active rheumatoid arthritis serum ferritin is the best blood test currently available for the
prediction of iron responsive anaemia. copyright. Key words: iron deficiency.
In patients with active rheumatoid arthritis (RA) ,ug/l indicated iron deficiency, as assessed by bone anaemia may be caused by the 'anaemia of chronic marrow examination, better than any other conven- disorders' and iron deficiency. The differential tionally used blood test (MCV, MCHC, serum iron, http://ard.bmj.com/ diagnosis between these two types of anaemia is plasma transferrin).3 Similar results have been potentially important but may be extremely difficult reported by others.' 2 4 5 unless bone marrow smears stained for iron are The present study was undertaken to examine if examined. The main reason for the difficulty is that serum ferritin in patients with RA could predict the usual blood tests indicating iron deficiency which patients would respond to iron therapy with a (mean cell volume (MCV), mean corpuscular rise in haemoglobin (Hb) concentration.
haemoglobin concentration (MCHC), serum iron) on September 28, 2021 by guest. Protected are affected similarly in the two types of anaemia. Materials and methods The magnitude of the problem is due to the fact that practically all patients with RA of a certain disease Ninety one patients from the Department of activity develop the anaemia of chronic disorders Rheumatology, Hvidovre Hospital, who all had and up to 75% of the same patients also have iron classical or definite RA according to the criteria deficiency.1 2 of the American Rheumatism Association were Serum ferritin is a good indicator of iron stores in treated with iron. Informed consent was obtained the organism and is valuable in the diagnosis of iron from all patients and approval obtained from the deficiency anaemia. Since it is also an acute phase local ethical committee. reactant it might a priori be of dubious value in RA. In 67 patients iron therapy was continued for the In a previous study we showed that in patients entire three months and laboratory values obtained with anaemia and RA serum ferritin levels below 60 before and after the therapy. There were 52 women and 15 men. Their ages ranged from 22 to 87 years various Accepted for publication 11 December 1985. (median 64 years). All the patients received Correspondence to Dr Troels M0rk Hansen, Kong Christian X's forms of antirheumatic therapy, including treatment Hospital, DK-6300 Graasten, Denmark. with disease modifying drugs. No patients had 596 Ann Rheum Dis: first published as 10.1136/ard.45.7.596 on 1 July 1986. Downloaded from
Serum ferritin as indicator of iron responsive anaemia 597 manifest bleeding or received blood transfusions patients, and ESR and CRP were higher. During during the study. iron therapy there was a decrease in plasma trans- All patients received ferrous sulphate tablets ferrin in both anaemic and non-anaemic patients. equal to 200 mg of iron daily The iron was given There was no change in the overall disease activity irrespective of the presence of anaemia. Twenty five as judged by an unchanged ESR and CRP during women and 10 men were anaemic at the start of the the three months. treatment, while 27 women and five men had Hb within the normal range. Discussion Laboratory investigations before and after three months of iron therapy included Hb, MCV, MCHC, This study has shown that in anaemic patients with serum iron, plasma transferrin, erythrocyte sedi- RA serum ferritin levels below 60 ig/l indicate iron mentation rate (ESR), and C reactive protein responsive anaemia with a rather high degree of (CRP) in serum according to routine practice at the accuracy (83%). Although MCV and plasma trans- hospital laboratory. Serum ferritin was measured ferrin scored comparably high percentages, it is with a radioimmunoassay kit from Clinical Assays, evident from Table 1 that serum ferritin would Cambridge, Mass., USA; the coefficient of variation diagnose more patients with iron deficiency anaemia was 8% than any other blood test. If the simultaneous A Student's t test, Fishers's test, and Spearman's presence of low serum ferritin and high plasma correlation test were used for the statistical analyses. transferrin were taken as evidence of iron deficiency anaemia, the predictive value would be further Results increased (to 91%), but again with a loss of the number of patients correctly defined as having iron The predictive values of the laboratory variables for deficient anaemia. None of the tests were of any changes in Hb in anaemic patients are given in Table value in predicting a negative response to iron 1; all changes in Hb were included. Serum ferritin therapy, and although low serum ferritin levels were <60 ig/l predicted an increase in Hb during iron found in several patients in the non-anaemic group, copyright. therapy in 83% (19/23) of the patients, while Hb the predictive value was too low to be of any clinical decreased in 50% (6/12) of the patients with serum value in predicting a rise in Hb concentration in this ferritin >60 ig/l (p<0 01). In non-anaemic patients group of patients. serum ferritin had no predictive value. Hb increased These results support our previous data which in 61% (11/18) of the patients with serum ferritin showed that serum ferritin was a good indicator of <60 [ig/l and decreased in 40% (4/10) of patients iron deficiency as assessed by bone marrow ex- http://ard.bmj.com/ with serum ferritin , 60 ,ug/l (p> 0-05). In four amination and further defined the clinical applica- patients with serum ferritin <60 ,ug/l the Hb was bility of this blood test in terms of its ability to unchanged during iron therapy. predict iron responsive anaemia in these patients.3 The results from the individual patients are given These results and those reported by others2 4 show in Tables 2a, b, and c. In Table 3 are given the group that serum ferritin is the best blood test for means and SEM. There was no difference in serum evaluating the iron status in patients with RA. It ferritin between anaemic and non-anaemic patients, needs to be considered whether it should replace
but serum ferritin increased during iron therapy. In bone marrow examination in this context. on September 28, 2021 by guest. Protected the anaemic patients MCHC, serum iron, and It is not completely clear why serum ferritin plasma transferrin were lower than in non-anaemic values above 60 ,ug/l could not predict a negative
Table 1 The predictive values oflaboratory variables for a rise or decrease in Hb during iron therapy in anaemic patients with rheumatoid arthritis
Predictive value of an abnormal Predictive value of a normal test test (Hb increase) (Hb decrease) Serum ferritin<60 tg/l 19/23=83% Serum ferritin:60 ILg/l 6/12=50% Serum iron<9 Fmol/I 20/28=71% Serum iron>9 1tmol/l 2/7=29% Plasma transferrin> 36 pmo/l 12/14=86% Plasma transferrin<36 umoUI 8/20=40% MCV<80 fl 5/6=83% MCV:80 fl 9/28=32% MCHC <19-0 mmoVI 9/13=69% MCHC>19.0 mmol/l 6/21=29% Ann Rheum Dis: first published as 10.1136/ard.45.7.596 on 1 July 1986. Downloaded from
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Downloaded from Serum ferritin as indicator of iron responsive anaemia 601 Table 3 Laboratory values before and after three months 50% of the non-anaemic patients showed a rise in of iron therapy* Hb concentration after three months of iron ther- apy, and 87% of all patients showed an increase in Before iron After three months of therapy iron therapy serum ferritin values. Also a significant decrease in plasma transferrin values after treatment was noted Hb females (mmoll); (Table 3). This indicates that functional iron de- anaemic 6.3±0-1 6-8±02 ficiency and iron deficiency anaemia were extremely non-anaemic §7-9±0 1 §81+±0 1 Hb males (mmol/l); common in our patients, in agreement with previous anaemic 7-2±0-2 7-9±0-3 experience.t-3 It also indicates that peroral iron is non-anaemic §9-6+0-5 §99+±0)2 readily absorbed in these patients, despite the Serum ferritin (Rg/l) simultaneous presence of the anaemia of chronic anaemic 60+11 91+16 non-anaemic 50±6 t 92+10 disorders, which is believed to be associated with a MCV (fl) decrease of iron absorption from the intestines.6 anaemic 90±2 89+1 The fact that no test could predict which of the non- non-anaemic 90±1 90+1 anaemic patients would show an increase in Hb MCHC (mmol/l) anaemic 19-1±0-2 19-2±0-3 concentration is probably due to the fact that iron non-anaemic §20-6+0-2 §205+±0)1 deficient erythropoiesis was not prominent in these Serum iron (,umoll) latter patients. Thus they had normal values for anaemic 8-2+1-2 13-0+2-5 MCV and MCHC and no significant increase in Hb non-anaemic §14-6+1-2 14-8+1-1 Plasma transferrin concentration after treatment (Table 3). (Rmol/l) This interpretation of our finding is not necessarily anaemic 36+1 t 32+1 at variance with that of Bentley and Williams, who non-anaemic §39+1 t §36+1 demonstrated a transient rise in Hb after parenteral ESR (mm/lst h) anaemic 63+6 53+7 iron treatment of patients with RA and anaemia.7 non-anaemic §28±4 §30±4 They suggested that patients with RA may, as a CRP (mg/I) rule, not be iron deficient. but that a relative iron copyright. anaemic 87+12 9(0+17 deficiency in the bone marrow may exist due to non-anaemic §37±6 §42+8 excessive entrapment of iron in the inflamed *Values are mean±SEM. synovial membrane. 'SI conversion: mmolIlxl6-1=g/l. In our previous study we found no correlation 'p 602 Hansen, Hansen Serum ferritin and the assessment of iron deficiency in 6 Boddy K, Will G. Iron absorption in rheumatoid arthritis. Ann rheumatoid arthritis. Scand J Rheumatol 1983; 12: 353-9. Rheum Dis 1969; 28: 537-40. 4 Blake D R, Waterworth R F, Bacon P A. Assessment of iron 7 Bentley D P, Williams P. Parenteral iron therapy in the stores in inflammation by assay of serum ferritin concentrations. anaemia of rheumatoid arthritis. Rheumatol Rehabil 1982; 21: Br Med J 1981; 283: 1147-8. 88-92. 5 Bentley D P, Williams P. Scrum ferritin concentration as an 8 Jacobs A, Miller F, Worwoos M, Beamish M R, Wardrop C A. index of stage iron in rheumatoid arthritis. J Clin Pathol 1974; Ferritin in the serum of normal subjects and patients with iron 27: 786-8. deficiency and iron overload. Br Med J 1972; iv: 206-8. copyright. http://ard.bmj.com/ on September 28, 2021 by guest. Protected