CLINICAL UTILITY OF SERUM FERRITIN

SIDDHARTH MED- 1ST YEAR

OUTLINE

SCOPE AND PURPOSE INTRODUCTION CLINICAL APPLICATION 1. Low serum ferritin 2. High serum ferritin TAKE HOME FLOW CHART

SCOPE AND PURPOSEFerritin measurements and corresponding

cut-offs facilitate the monitoring of iron deficiency trends and the assessment of

the impact of health and nutrition interventions.

Goal is to prevent and control iron deficiency and provide the basis for

advocacy programs for iron deficiency and anemia prevention in vulnerable

populations.

INTRODUCTION Its an iron storage protein.

Its primary role is in iron sequestration.

Iron is toxic, because of its capacity to generate reactive species, which has the capacity to damage DNA and proteins.

Normal range: 50-200 ug/L.

CLINICAL APPLICATIONSLOW

SERUM FERRITI

N

1. Most useful in

iron deficiency (<15ug/L)

2. Hypothyroidism

3. Ascorbate deficiency

PHYSIOLOGY

IRON DEFICIENCY ANEMIACAUSES:

1. Increase demand for iron:

-Infancy, adolescence, pregnancy,

erythropoietin therapy.

2. Increased iron loss:

-Acute/chronic blood loss, menses,

blood donation & phlebotomy.

3. Decreased iron intake/absorption

CONT…. LAB FINDINGS: DECREASED INCREASED

1. Hb, PCV, MCV, MCH 1. TIBC (>400 ug/dl)

2. SERUM IRON (< 30 ug/dl) 2. TRANSFERRIN RECEPTOR PROTEIN

3. SERUM FERRITIN (< 15 ug/L) 3. RED CELL PROTOPORPHYRIN (> 100ug/dl)

4. TRANSFERRIN SATURATION (<10 %)

4. RDW

5. BONE MARROW IRON STORES

CONT….

RE iron stores can be estimated from iron stain of bone marrow aspirate or biopsy ( gold std ).

This is largely “replaced by measuring serum ferritin levels”.

Serum ferritin level is a better indicator of iron overload than the marrow stain.

CONT….IRON STORES FERRITIN

LEVELS (ug/L)MARROW IRON STAIN

0 < 15 0

1-300 mg 15-30 TRACE TO 1+

300-800 mg 30-60 2 +

800-1000 mg 60-150 3 +

1-2 g > 150 4 +

IRON OVERLOAD > 500 - 1000 -

CLINICAL IMPORTANCETESTS IRON

DEFICIENCYINFLAMMATION

ANEMIA MILD TO SEVERE MILD

MCV 60-90 80-90

SERUM IRON <30 <50

TIBC >360 <300

SATURATION (%) < 10 10-20

FERRITIN (ug/L) <15 30-200

IRON STORES 0 2-4 +

CLINICAL APPLICATIONSHIGH SERUM

FERRITIN

1. Iron overload

2. Acute inflammatory

conditions

3. Liver disease

4. Alcohol excess

CAUSES OF IRON OVERLOADPRIMARY:

• - Hereditary hemochromatosis• - Hereditary aceruloplaminemia

SECONDARY:

• -Transfusion overload• - Excess dietary iron• - Porphyria cutanea tarda• - Ineffective erythropoiesis

HERIDITARY HEMOCHROMATOSES

Autosomal recessive disorder with mutation in HFE gene (substitution of tyrosine for cysteine at amino acid 282.

Homozygous patients have 50-75 % chance of developing iron overload.

Hetrozygous are unlikely to develop the disease, but transmit gene mutation to the children.

CONT….

Routine screening is recommended in first degree relatives of patients with confirmed diagnosis.

Screening involves use of ferritin and transferin saturation. Current recommendation suggest elevated ferritin with TSAT >45% should prompt genetic confirmation.

Levels >1000 ug/L usually poses high risk for cirrhosis.

WILSONS DISEASE

Rare disorder due to mutation in chromosome 13.

It causes marked hyperferritinemia as well as copper overload.

It can be distinguished from HH by low serum transferrin saturation and an undetectable serum ceruloplasmin concentration.

SECONDARY IRON OVERLOAD

Chronic transfusion therapy is a mainstay of therapy for children and adults with thalassemia major. Iron gets deposited first in RE system prior to loading within the heart and liver. It ultimately results in heart & liver failure.

Excessive intake of dietary iron.

CONT….

Porphyria cutanea tarda usually manifests as cutaneous photosensitivity and hepatic iron overload. It is diagnosed by increased urinary and fecal porphyrin excretion.

HIGH FERRITIN WITHOUT IRON OVERLOAD

Liver disease- NASH, Viral hepatitis

Alcohol excess

Rheumatoid arthritis, IBD

Bacterial infection

Malignancy & thyrotoxicosis

ANEMIA OF CHRONIC DISEASE

Associated with release of pro-inflammatory cytokines & hepcidin.

Features of anemia are brought about by inadequate iron delivery to the marrow, despite normal or increased iron stores.

Typically serum ferritin levels increase by threefold over basal levels.

CONT….CHRONIC INFECTIONS:

- HIV, Osteomyelitis, Tuberculosis

COLLAGEN VASCULAR DISEASE:

- SLE, RA, POLYMYOSITIS, POLY ARTERITIS NODOSA

CKD, IBD

MALIGNANCY

INFLAMMATORY CONDITIONS

STILLS DISEASE:

1. Characterized by fever, arthritis & rash. 2. Elevated serum ferritin levels were seen in 89 % of these patients in recent

series.3. Whether disproportionate ferritin response is a pathogenic mechanism or

is a by- product of inflammation remains

unknown.

LIVER DISEASES STEATOHEPATITIS: - Increased ferritin with normal

tranferrin saturation is seen with hepatic steatosis.

- It is thought to be due to the combination of disrupted glucose, lipid and iron metabolism.

CONT… VIRAL HEPATITIS:

- Hepatitis A,B,C,D, EBV & CMV will cause an elevation in serum ferritin indicative of liver inflammation.

- Chronic hepatitis C or B may be less obvious clinically & serologies should be checked if there is minimal disturbance of liver enzymes in cases of unexplained hyperferritinemia.

ALCOHOL EXCESS Regular alcohol consumption is

responsible for disruption of normal iron metabolism.

It results in excess iron deposition in the liver, in one third of alcohol subjects.

This elevation of serum ferritin can occur without elevation of other liver enzymes.

TAKE HOME FLOW CHART

REFERENCES

HARRISONS PRINCIPLES OF INTERNAL MEDICINE.

WINTROBE’S CLINICAL HEMATOLOGY

WILLIAMS MANUAL OF HEMATOLOGY

ASSOCIATION OF HEMATOLOGY 2014

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