BritishJournal ofHaeaemafology, 1975, 31,

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Annotation THE CLINICAL USE OF SERUM FERRITIN ESTIMATION The structure, function and biochemistry of ferritin have recently been reviewed (Harrison et nl, 1974) and an account of the clinical and biochemical significance of circulating ferritin has also appeared (Jacobs & Worwood, 1975). This review deals only with the clinical application of the immunoradiometric assay for ferritin which has been available for the last 3 years (Addison et 01, 1972) and has recently been adapted for automation (Worwood & Jones, 1975). Other labelled antibody assays for ferritin have been described by Miles et al (1974) and by Halliday ct nl (1975). The practical assessment of total body iron stores has always been a compromise between quantitation and convenience. The most direct method for measuring storage iron is by quantitative phlebotomy (Jacobs, 1974) and the results obtained by this technique provide a standard for comparison with' other methods. The alternative methods involve the injection of chelating agents such as desferrioxamine followed by the measurement of urinary iron excretion or the estimation of iron in biopsy samples, either visually or chemically. All these procedures involve the patient in some inconvenience. In addition chelatable iron is not always directly rclatcd to storage iron. Estimation of serum ferritin concentration has proved a useful method of assessing iron stores which is quantitative, reproducible and requires only a small blood sample from the patient. I n healthy adults the concentration of ferritin in serum is directly related to the available storage iron in the body. The mean concentration is higher in men (123 pg/l.) thanin women (56 lig/l.) with a range between 12 and 300 pg/l. (Jacobs& Worwood, 1975). In patients with iron deficiency anaemia concentrations are below I Z pg/l. and in patients with iron overload the concentration may be as high as 10000 pg/l. (Jacobs & Worwood, 1975). hi normal subjects there is a good correlation between serum ferritin concentration and iron stores mobilized by quantitative phlebotomy (Walters et a!, 1973). In patients with transfusion siderosis the serum ferritin concentration is related to the amount of blood given and a good correlation has also been shown between serum ferritin concentration and the concentration of iron in liver biopsy tissue (Letsky at al, 1974). The visual estimation of stainable iron in the bone marrow is probably the most commonly used method for assessing iron stores in clinical practice but it has the disadvantage of being subjective, semi-quantitative and has a relatively poor reproducibility. Comparison with serum ferritin concentration shows a crude relationship between the two indices (Bentley & Williams, 1974; Hussein et a!, 197s) but the ferritin assay has the advantage of providing quantitative and reproducible results and is more sensitive than the histo-chemical method in detecting low iron stores. Serum ferritin concentration can be used both to evaluate iron stores in patients with suspected iron deficiency and to determine the level of stores after the completion of iron therapy (Bentley &Jacobs, 1975). It is particularly useful for measuring iron stores in patients with chronic disease such as rheumatoid arthritis who may also have a hypochromic microcytic anaemia (Bentley & Williams, 1974) and in these cases it is the most effective way to Correspondence: Professor A. Jacobs, Department of Haematology, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XW.

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determine the need for iron therapy. It has also been used in monitoring tlie iron status of patients with chronic renal failure on a regular dialysis regime (Hussein et al, 1975) and here too iron tlicrapy can be controlled in a rational manner. Iron ovcrload can be monitored by serial estimations of serum ferritin concentration and in patients with idiopathic haemochroniatosis who are undergoing vencscction the assay will show when body iron storcs have bccn fully mobilized. In patients with thalassaemia who have bcen on a regular transfusion regime the effect of chelation therapy can be assessed (Letsky et a2, 1974). The scruni ferritiii concentration usually reflects reticuloendothelial storage iron. Changes in rcticuloendothelial iron are followed rapidly by changes in the serum concentration of ferritin. In normal subjects undergoing venesection the serum ferritin conccntration falls rapidly as storage iron is mobilized for haenioglobin synthesis (Jacobs et al, 1972). In the anaemia of chronic disease where a low serum iron concentration is associated with increased stainable iron in marrow RE cells tlie serum iron concentration is no longer a valid index of iron deficiency. The shift of iron from the transferrin and red cell compartments into the storage pool is reflected by a rise in the serum ferritin concentration. This phenomenon has been seen both in rheumatoid arthritis (Bentley & Williams, 1974) and Hodgkin’s diseasc (Jones et nl, 1973). Siimes et a1 (1974) have shown that the ferritin concentration in serum from cord blood is similar to that in serum from normal adult males but during the first month of life there is a sharp rise in serum ferritin concentration as the haemoglobin concentration falls and iron shifts from the red cell to the storage compartment. This is followed by an equally sharp fall in serum ferritin as storage iron is utilized for erythropoiesis later in infancy. From the age of 6 months to puberty serum ferritin concentrations remain at a relatively low lcvcl with a median concentration of 30 &l. The concentration of circulating ferritin dcpends on its release from tissues (Jacobs & Worwood, 1975). In iron deficiency or overload the conceiitratioii in serum is related to the concentration in the tissues but it should be noted that in patients with tissue damage or inalignancy the relationship with iron status may be overshadowed by variations due to tlic abnormal production or release of tlic protein and possibly by variations in plasma clearance. Serum fcrritin concentration may be increased in patients with acute or chronic liver disease (Prieto ct a / , 1975), the highest values being found in viral hepatitis or drug induced hepatic necrosis. In acute leukaemia high serum fcrritin levels are associated with increased synthesis of the protcin by leukaeniic cells (Jacobs & Worwood, 1975) but this phenomenon has not yet been shown to have any value in clinical management. In acute lyniphoblastic leukaemia those children who are able to sustain a remission without chemotherapy usually regain their normal serum conccntrations (Parry et al, 1975). In many patients with malignant disease an increase in serum ferritin associated with a low serum iron concentration may be expected as a non-specific phenomenon. The only clinical use of tlic serum ferritin assay at the present time is in the measurement of iron stores. It has considerable advantages over the estimation of serum iron in the diagnosis of iron deficieiicy and it has relieved tlie patient of the need to have a marrow puncturc whcn this is carried out purely for the assessment of iron status. Dcpartriierit of Haematology, A. JACOBS Welsh National School of Medicine, M . WORWOOD

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REFERENCES ADDISON,G.M., BEAMISH,M.R., HALES, C.N., HODGK~NS, M., JACOBS, A. & LLEWZLIN,P. (1972) An iminunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. Journal d Clinical Pathology, 25, 326. BENTLEY, D.P. &JACOBS, A. (1975) Accumulation of storage iron in patients treated for iron deficiency anaemia. Britkh Medical]onrnal, E, 64. BENTLEY, D.P. & WILLIAMS, P. (1974) Serum ferritin concentration as an index of storage iron in rheumatoid arthritis. Journal of Clinical Pathology, 27, 786. HALLIDAY, J.W., GERA,K.L.& POWELL, L.W. (197s) Solid phase radioimmunoassay for serum ferritin. CIinical Chimica Acta, 58, 207. HARRISON, P.M., HOARE,R.J., HOY, T.G. & MACARA, LG. (1974) Ferritin and haemosiderin: structure and function. In: Iron in Biochemistry and Medicine (Ed. by A. Jacobs and M. Worwood). Academic Press, London. S.,PRIETO, J., O’SHEA,M., HOFFBRAND, A.V. HLJSS~DI, J.F. (1975) Serum ferBAILLOD, R.A. & MOORHEAD, ritin assay and iron status in chronic renal failure and haemodialysis. British Medical Journal, i, 546. JACOBS,A., (1974) Erythropoiesis and iron deficiency anaemia. In: Iron in Biochemistry and Medicine (Ed. by A. Jacobs and M. Wonvood). Academic Press, London. M. (1975) Ferritin in serum. JACOBS, A. & WORWOOD, Clinical and biochemical implications. New England Journal ?fMedicine, 292, 951. JACOBS, A., MILLER,F., WORWOOD, M., BEAMISH, M.H.& WARDROP,C.A. (1972) Ferritin in the

serum of normal subjects and paticnts with iron deficiency and iron overload. British Medical Journal, iv, 206. JON=, P.A.E., MILLER,F.M., WORWOOD,M. & JACOBS,A. (1973) Ferritinaemia in leukaemia and Hodgkin’s disease. British Journal of Cancer, 27, 212.

E.A., MILLER,F., ORW WOOD, M. PC FLYNN, D.M. (1974) Serum ferritin in children with thalassaemia regularly transfused. Journal o j Clinical Pathology, 27, 652. MILES, L.E.M., LIPSCHITZ,D.A., BIEBER,C.P. & COOK, J.D. (1974) Measurement of serum ferritin by a m i t e immunoradiometric assay. Analytical Biochemistry, 61, 2og. PARRY,D.H., WORWOOD, M. &JACOBS,A. (1975) Serum ferritin in acute leukaemia at presentation and during remission. British Medical Journal, i, 245. PRIETO, J., BARRY,M. & SHERLOCK, S. (1975) Serum ferritin in patients with iron overload and with acute and chronic liver disease. Gastroenterology, LBTSKY,

68, 525.

SIIMES,M.A., ADDIEGO, J.E., JR & DALLMAN, P.R. (1974) Ferritin in serum: Diagnosis of iron deficiency and iron overload in infants and children. Blood, 43, 581.

WALTERS, G.O., MILLER,F. & WORWOOD,M. (1973) Serum fcrritin concentration and iron stores in normal subjects. Journal of Clinical Pathology, 26, 770.

WORWOOD, M. &JONES,B. (1975) An automated immunoradiometric assay for ferritin. Journal .f Clinical Pathology (in press).

The clinical use of serum ferritin estimation.

BritishJournal ofHaeaemafology, 1975, 31, I. Annotation THE CLINICAL USE OF SERUM FERRITIN ESTIMATION The structure, function and biochemistry of fe...
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