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Serum Ferritin Testing for Iron Overload
The most commonly used test for estimating iron burden is plasma or serum ferritin concentration. These markers rise or fall in the same direction as iron stores increase or decrease, and also provide a rough estimate of the total body iron stores. For the foreseeable future, it seems that this test will remain a mainstay of clinical practice due to its simplicity and widespread use.
Serum ferritin has a "polar" predictive value:
- Low levels indicate normal pathology; <300 mcg/L is within the limit of normal for a male, while <150 mcg/L is within the normal limit for a menstruating female.
- Consistently high levels indicate high iron burden (serum ferritin levels >1000 mcg/L).
Predictive value of serum ferritin levels
Although the predictive value of serum ferritin for serious complications of iron overload may vary according to the mechanism of iron loading, a threshold serum ferritin level of 1000 mcg/L is associated with serious clinical sequelae in both hereditary hemochromatosis and transfusional iron overload.
Among patients with hereditary hemochromatosis, cirrhosis is much more prevalent in those with serum ferritin >1000 mcg/L than in those below this level;(1) serum ferritin <1000 mcg/L is associated with absence of cirrhosis.(2) A retrospective analysis of deaths due to cardiac and liver failure in patients with myelodysplastic syndromes or aplastic anemia showed that 97% had serum ferritin levels >1000 mcg/L.(3) Serum ferritin >1000 mgc/L on repeated measurements has been proposed as the threshold for initiation of iron reduction therapy in transfusion-dependent patients.(4)
Relationship between elevated serum ferritin and overall hazard ratio in MDS5Relationship between elevated serum ferritin and overall hazard ratio in MDS5
After adjusting for transfusion burden, there was a hazard ratio of 1.3 for every 500 mcg/L increase in serum ferritin above 1000 mcg/L.
Adapted with permission from Malcovati, et al.(5)
Serum ferritin concentrations regularly in excess of 2500 mcg/L have been correlated with substantially worsened cardiac prognosis when maintained over long periods of time.(6)
Advantages of serum ferritin
The noninvasiveness, wide availability, and low cost of serum ferritin testing allow for regular monitoring of iron burden, facilitating ongoing monitoring over time. Serum ferritin levels are positively associated with morbidity and mortality in both primary and secondary iron overload.
Disadvantages of serum ferritin
Ferritin values may be complicated by a number of factors, chiefly inflammation.(7) Other confounding factors include ascorbate deficiency, hepatic damage, hemolysis, and ineffective erythropoiesis.(8) Over time, serum ferritin rises or falls in the same direction as iron stores, and repeated measurements provide a more reliable estimate of total body iron stores than single measurements.
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Serum Ferritin
>1000 mcg/L in MDS
A consensus panel of MDS experts recommends treating iron overload when serum ferritin is >1000 mcg/L.
Learn moreReferences
- (1) Morrison ED, Brandhagen DJ, Phatak PD, et al. Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis. Ann Intern Med. 2003;138:627-633.
- (2) Schmitt B, Golub RM, Green R. Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level: systematic review for the American College of Physicians. Ann Intern Med. 2005;143:522-536.
- (3) Takatoku M, Uchiyama T, Okamoto S, et al. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol. 2007;78:487-494.
- (4) Porter JB, Practical management of iron overload. Br J Haematol. 2001;115(2):239-52.
- (5) Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome [editorial]. Haematologica. 2006;91:1588-1590.
- (6) Olivieri NF, Nathan DG, MacMillan JH, et al, Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994;331(9):574-8.
- (7) Brittenham GM, Badman DG, Noninvasive measurement of iron: report of an NIDDK workshop. Blood. 2003;101(1):15-9.
- (8) Roeser HP, Halliday JW, Sizemore DJ, et al, Serum ferritin in ascorbic acid deficiency. Br J Haematol. 1980;45(3):459-66.