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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 PURPOSE
Ferritin 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 APPLICATIONS
LOW SERUM
FERRITIN
1. Most useful in
iron deficiency
(<15ug/L)
2. Hypothyroidism
3. Ascorbate
deficiency
PHYSIOLOGY
IRON DEFICIENCY ANEMIA
CAUSES:
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 IMPORTANCE
TESTS IRON
DEFICIENCY
INFLAMMATION
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 APPLICATIONS
HIGH
SERUM
FERRITIN
1. Iron overload
2. Acute
inflammatory
conditions
3. Liver disease
4. Alcohol excess
CAUSES OF IRON
OVERLOAD
• - Hereditary hemochromatosis
• - Hereditary aceruloplaminemia
PRIMARY:
• -Transfusion overload
• - Excess dietary iron
• - Porphyria cutanea tarda
• - Ineffective erythropoiesis
SECONDARY:
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
3.
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
THANK YOU

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Clinical utility of serum ferritin

  • 1. CLINICAL UTILITY OF SERUM FERRITIN SIDDHARTH MED- 1ST YEAR
  • 2. OUTLINE  SCOPE AND PURPOSE  INTRODUCTION  CLINICAL APPLICATION 1. Low serum ferritin 2. High serum ferritin  TAKE HOME FLOW CHART
  • 3. SCOPE AND PURPOSE Ferritin 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.
  • 4. 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.
  • 5. CLINICAL APPLICATIONS LOW SERUM FERRITIN 1. Most useful in iron deficiency (<15ug/L) 2. Hypothyroidism 3. Ascorbate deficiency
  • 7. IRON DEFICIENCY ANEMIA CAUSES: 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
  • 8. 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
  • 9.
  • 10.
  • 11. 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.
  • 12. 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 -
  • 13.
  • 14. CLINICAL IMPORTANCE TESTS IRON DEFICIENCY INFLAMMATION 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 +
  • 15.
  • 16. CLINICAL APPLICATIONS HIGH SERUM FERRITIN 1. Iron overload 2. Acute inflammatory conditions 3. Liver disease 4. Alcohol excess
  • 17. CAUSES OF IRON OVERLOAD • - Hereditary hemochromatosis • - Hereditary aceruloplaminemia PRIMARY: • -Transfusion overload • - Excess dietary iron • - Porphyria cutanea tarda • - Ineffective erythropoiesis SECONDARY:
  • 18. 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.
  • 19. 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.
  • 20. WILSONS DISEASE Rare disorder due to mutation in chromosome 3. 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.
  • 21. 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.
  • 22. CONT…. Porphyria cutanea tarda usually manifests as cutaneous photosensitivity and hepatic iron overload. It is diagnosed by increased urinary and fecal porphyrin excretion.
  • 23. HIGH FERRITIN WITHOUT IRON OVERLOAD  Liver disease- NASH, Viral hepatitis  Alcohol excess  Rheumatoid arthritis, IBD  Bacterial infection  Malignancy & thyrotoxicosis
  • 24. 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.
  • 25.
  • 26. CONT…. CHRONIC INFECTIONS: - HIV, Osteomyelitis, Tuberculosis COLLAGEN VASCULAR DISEASE: - SLE, RA, POLYMYOSITIS, POLY ARTERITIS NODOSA CKD, IBD MALIGNANCY
  • 27. 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.
  • 28. 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.
  • 29. 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.
  • 30. 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.
  • 31. TAKE HOME FLOW CHART
  • 32. REFERENCES  HARRISONS PRINCIPLES OF INTERNAL MEDICINE.  WINTROBE’S CLINICAL HEMATOLOGY  WILLIAMS MANUAL OF HEMATOLOGY  ASSOCIATION OF HEMATOLOGY 2014