Ix of a raised serum ferritin (BSH 2018)

N.B. These notes are specifically regarding ferritin - see here for a more general iron overview.

 

Intro

 

In health, serum ferritin is directly proportional to iron stores (1ug/l ferritin = 8mg storage iron)

 

Ferritin

 

A soluble protein which provides intracellular storage of bio-available iron

Found primarily in the liver, spleen and marrow macrophages but is present in all cells of the body

Made up of heavy (H) and Light (L) subunits, which are encoded by two separate genes

(e.g. the lens of the eye produces only L chain ferritin, which can precipitate into crystals (see later))

 

(Haemosiderin is denatured, insoluble ferritin seen as ‘stainable iron’ in macrophages.)

 

Serum Ferritin (SF)

 

SF plays no role in iron transport or cellular uptake.

 

SF is largely glycosylated, a process which occurs intracellularly, and it is therefore assumed that SF is a secreted plasma protein (but the mechanism or function of this is not known)

 

Non-glycosylated SF is thought to be intracellular tissue ferritin which has leaked out into the plasma.

 

The ratio of glycosylated/non-glycosylated ferritin is different depending on the underlying condition.

  • E.g. There is a low proportion of glycosylated ferritin in liver necrosis or Still’s disease (tissue leak), compared to a high proportion in hereditary haemochromatosis (excess of a secreted plasma protein)

 

Measured by ELISA technique

Causes of a Raised SF

 

Iron accumulation

  • Excess intake – e.g. iatrogenic (RBC transfusion), excess in diet

  • Hereditary hyperferritinaemias –e.g. hereditary haemochromatosis

  • Ineffective erythropoiesis – e.g. MDS, Thalassaemia

  • Other – atransferritinaemia, ferroportin disease

Increase ferritin production in absence of iron accumulation

  • Acute phase response – e.g. infection, inflammation, tissue damage

  • Malignancy

  • Gaucher disease

  • Chronic inflammation – e.g. metabolic syndrome, AI conditions

Increased ferritin as a result of cell damage

  • Liver disease – necrosis, alcohol, hepatitis etc

 

N.B. Upper limit of normal?

Varies with age, sex and ethnicity

20% of white adult males have a SF >300ug/l

Asymptomatic SF >1,000 ug/l is 2-3x more common in African/Asian ethnicity than White/Hispanic.

 

Assessment of Hyperferritinaemia

 

Questions:

Is it secondary to a known clinical condition?

Is it associated with iron overload?

 

Raised serum ferritin >300/>200 ug/l (male/female): 

  • TSats <50%/<40% (male/female) --> Consider causes other than iron accumulation

  • FBC normal, TSats >50%/>40% (male/female) --> Test HFE genotyping (these patients have a 15-20% chance of being C282Y homozygotes)

  • FBC abnormal, TSats >50%/>40% (male/female) --> Consider iron loading anaemia

 

Even with a SF >1500 ug/l liver disease, alcohol, inflammatory disorders, malignancy, renal failure and haematological disorders are all still more common than genetic hyperferritinaemia when SF is checked in primary care.

 

Levels of SF >10,000 ug/l should prompt consideration of rare disorders such as HLH or Still disease, but the other common causes listed above can still be responsible

 

Rare diseases associated with raised SF

See here

 

Chronic Kidney disease (NICE 2015)

 

SF is not useful in CKD – elevated in 50% of patients on haemodialysis but not reflective of bioavailable iron

SF + transferrin saturation (TSat) should be not be used in isolation to assess need for iron replacement in CKD

New tests include: % Hypochromic red cells (%HYPO) or reticulocyte haemoglobin concentration (CHr)

 

CKD patients on erythropoietin with a SF <800 should be offer iron supplementation with a target of %HYPO <6% or CHr <29pg or TSats >20%