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Serum Ferritin As Indicator of Iron Responsive Anaemia in Patients with Rheumatoid Arthritis

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Serum Ferritin As Indicator of Iron Responsive Anaemia in Patients with Rheumatoid Arthritis 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 598 Hansen, Hansen a, C -C "t ,I I) M >- IC V) -'Mr4 : OC ,t Cr' C-V Nm,I, et r ' cce _ eO v: N e'-^e C _N -00x C00V Z V N t-04e0n C0xNx ON 00 0 O__NO 1tr~ N - £ ON N fI N00 - m CINC OC O In00 N t ICx X OO cq ~ ~~~~O t X ~~t mvn 4X- U:m m m m O ms mOO m C- W' m Cs :t "t m x 'I - tl r- ) 'IC 'I o^-c m V) eN 'IC m 'I x 'I 'I 'I 'IC .?*t < oj t t t ^ e t N < ^ N < N < ON'IN r-e "C<N, --V NVVV V-V VVVV 61 E~~~~~~~~~~~~ copyright. x~ ~~~ - -ows-<eoe- -ct- - .z2- W0 0 N M - 0~- V VV VV v -vC4 E .?O ~~~~~~~~~-0al r- CN x x m N C7 <0x x a, c, r- x ON 00x xsx 00 CN e ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.=I! >~~~~~~~~~I"Itx m~"I 'I NV-V)V V, V V VV V a, S~~40 ~~~~~r X 1-1 a,o oXX a, o-c0ON r-v :_o C\ , oN oN -<O0 us X C: ~~~ONNON00000bONONO0 00 000NC N0 0N00 0 0 00 0 00N0 N http://ard.bmj.com/ c:~~v)O~~~~~~~~a£ £DXcNv £ x£ 11 m tO n"r£ £en f C toCC x~~~ ~ ~~~~~~Ix q,Ci,, M ? X (\°° °° °°, r- CI*t ?, ,: r ** ~~~~~~~~~ ~~~~~~~E 'e o x,r cs, r:, 09 9 E on September 28, 2021 by guest.
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