Iron Studies, Ferritin, Immunoglobin

Question 1

What are the Iron Studies used for? Normal values?

Answer 1

Used to evaluate iron metabolism in patients when iron deficiency, overload, or poisoning is suspected.
Tests include serum iron level, total iron binding capacity (TIBC), transferrin, and transferrin saturation.

Normal Findings
Iron: Male 80-180 mcg/dL; Female: 60-160 mcg/dL
TIBC: 250-460 mcg/dL
Transferrin: Male 215-365 mg/dL; Female 250-380 mg/dL
Transferrin Saturation: Male 20-50%; Female 15-50%

Question 2

What does iron deficiency cause?

Answer 2

Iron deficiency causes decreased hemoglobin production leading to microcytic hypochromic RBCs as well as decreases in MCV and MCHC. The serum iron level is decreased, TIBC is elevated, and transferrin saturation is low.

Question 3

What is Serum Iron measuring?

Answer 3

Serum iron is a measurement of the iron bound to transferrin

Question 4

What is Iron overload or poisoning?

Answer 4

Iron overload or poisoning is called hemochromatosis or hemosiderosis with excessive iron deposited in the brain, liver, and heart to cause severe dysfunction of these organs.

Question 5

When should Serum Iron levels be drawn?

Answer 5

Serum iron levels should be drawn in the AM as eating may artificially elevate iron measurements if food had high iron content

Question 6

What is TIBC?

Answer 6

TIBC is a measurement of all proteins available for binding iron.

TIBC is an indirect measurement of transferrin, but ferritin is not included in TIBC as it binds only stored iron

TIBC is used to monitor patients during hyperalimentation

Question 7

What is Transferrin?

Answer 7

Transferrin is the largest quantity of iron binding proteins.

Transferrin is a negative acute phase reactant protein so levels decrease with inflammatory reactions.

Question 8

How do you measure the TIBC?

Answer 8

TIBC is measured by adding excess iron to the patient’s serum - this saturates all the transferrin. Excess iron is removed and the iron that is left is a direct measurement of TIBC and an indirect measurement of transferrin

TIBC varies minimally with iron intake and is more of a reflection of liver function (transferrin is made by the liver) and nutrition than of iron metabolism

Question 9

What is TIBC and Transferring Saturation?

Answer 9

The percentage of transferrin and other mobile iron-binding proteins saturated with iron is calculated by dividing the serum iron level by the TIBC. Normal is 20-50%.

This is helpful in determining the cause of abnormal iron and TIBC levels. Transferrin saturation is < 15% in iron deficiency anemia and is increased with hemolytic, sideroblastic, or megaloblastic anemias as well as iron overload or iron poisoning.

Question 10

What are the Interfering Factors of the Iron Studies?

Answer 10

Recent transfusions may increase serum iron.
Recent ingestion of food high in iron may increase serum iron.
Hemolytic diseases may have an artificially high iron content.
Drugs that increase iron levels include estrogens, ethanol, iron preparations, oral contraceptives.
Drugs that decrease iron levels include ACTH, cholestyramine, colchicine, deferoxamine, and testosterone.
Drugs that increase TIBC include fluorides and oral contraceptives.
Drugs that decrease TIBC include ACTH and chloramphenicol

Question 11

What causes Increased levels of Serum Iron?

Answer 11

Hemosiderosis or hemochromatosis
Iron poisoning.
Hemolytic anemia – iron in hemoglobin of hemolyzed RBCs leaks out.
Massive blood transfusions – 1 mg of iron per ml of packed RBCs.
Hepatitis or hepatic necrosis.
Lead toxicity – lead overload displaces iron stores

Question 12

What causes Decreased levels of Serum Iron?

Answer 12

Insufficient dietary iron – all body iron is from dietary intake, so a reduced intake will eventually lead to reduced levels.

Chronic blood loss (irregular menses, uterine cancer, GI cancer, inflammatory bowel disease, diverticulosis, urologic tract cancer (hematuria), hemangioma, AVM – chronic blood loss depletes iron because most of iron exists in hemoglobin in RBCs.

Inadequate intestinal absorption of iron (malabsorption, short bowel syndrome) – all iron in body is from dietary intake.

Pregnancy (late) – fetal requirements deplete mother’s store of iron.

Iron deficiency anemia

Neoplasm

Question 13

What causes Increased levels of TIBC or Transferrin ?

Answer 13

Estrogen therapy
Pregnancy (late)
Polycythemia vera
Iron deficiency anemia

Question 14

What causes Decreased levels of TIBC or Transferrin ?

Answer 14

Malnutrition, hypoproteinemia – transferrin is a protein and will decrease as protein is depleted.

Inflammatory diseases, cirrhosis – transferrin is a negative acute phase reactant protein so will decrease with acute inflammatory reactions.

Hemolytic anemia, pernicious anemia, sickle cell anemia – have elevated iron levels and decreased TIBC

Question 15

What causes Increased levels Transferrin Saturation?

Answer 15

Hemochromatosis or hemosiderosis, increased iron intake – increased iron saturates transferrin.

Hemolytic anemias – iron is increased and saturates transferrin

Question 16

What causes Decreased levels Transferrin Saturation?

Answer 16

Iron deficiency anemia, chronic illnesses (malignancy, other chronic illnesses) – iron levels are low so transferrin levels are increased.

Question 17

What is Ferritin mainly used for? Normal values?

Answer 17

Most sensitive test to determine iron deficiency anemia.

Normal Ranges: Male 12-300 ng/mL; Female 10-150 ng/mL

Question 18

What can Ferritin also be used for?

Answer 18

Ferritin test also used in patients with chronic renal failure to monitor iron stores

Ferritin can act as an acute phase reactant protein so may be elevated in non-iron related conditions (acute inflammatory diseases, infections, metastatic cancer, lymphomas). Elevations occur 1-2 days after onset of acute illness and peaks at 3-5 days. If iron deficiency also exists in these patients, it may not be recognized with a factitious elevation by the concurrent disease

Question 19

What is Ferritin?

Answer 19

Ferritin is the major iron storage protein and is present in serum in concentrations directly related to iron storage. In normal patients, 1 ng/mL of serum ferritin corresponds to 8 mg of stored iron.

Decreases in ferritin levels indicate a decrease in iron storage (iron deficiency anemia) with a level less than 10 being diagnostic.

Decrease in ferritin will often occur before other signs such as decreased iron levels or change in RBC count or indices.

Question 20

What are the Interfering Factors of Ferritin?

Answer 20

Recent transfusions or recent ingestion of a meal high in iron can cause elevated ferritin – ingested iron stimulates ferritin production.
Recent administration of radionuclide can cause abnormal levels.
Hemolytic diseases may have artificially high iron content due to hemolyzed RBCs – ferritin synthesis increased to store the iron.
Acute and chronic inflammatory diseases can falsely increase levels.
Disorders of excess iron storage (hemochromatosis, hemosiderosis) have high ferritin levels.
Iron deficient menstruating women may have decreased ferritin levels.
Iron preparations may increase ferritin levels

Question 21

What causes increased levels of Ferritin?

Answer 21

Hemochromatosis, hemosiderosis – increased iron stores.
Megaloblastic anemia, hemolytic anemia – RBCs lyse to release iron.
Alcoholic/inflammatory hepatocellular disease, inflammatory disease, advanced cancers – ferritin is an acute phase reactant protein.
Chronic illnesses like leukemia, cirrhosis, chronic hepatitis, or collagen vascular diseases.

Question 22

What causes decreased levels of Ferritin?

Answer 22

Iron deficiency anemia – iron stores are decreased so less ferritin is required.

Severe protein deficiency – ferritin synthesis is reduced.

Hemodialysis – iron stores are reduced by dialysis

Question 23

What is Immunoglobin Electrophoresis used for? Normal values?

Answer 23

Used to assist in diagnosis and monitoring of therapeutic response in many diseases – ordered if serum protein electrophoresis indicates a spike at the immunoglobulin level.

Normal ranges:
IgG: 565-1765 mg/dL
IgA: 85-385 mg/dL
IgM: 55-375 mg/dL
IgD and IgE: minimal

Question 24

What are the proteins in the blood made of?

Answer 24

Proteins in the blood are made up of albumin and globulin. One type of globulin is gamma globulins.

Antibodies are made of gamma globulins and are called immunoglobulins.

Question 25

What are the classes of the Immunoglobins?

Answer 25

IgG

IgM

IgA

IgE

IgD

Question 26

What is IgG?

Answer 26

75% of serum immunoglobulins. Maternal IgG can cross the placenta and is effective for immune protection of the newborn the first few months of life

Question 27

What is IgM?

Answer 27

responsible for ABO blood grouping and rheumatoid factor. Also involved in immunologic reactions to many infections (hepatitis, gram negative sepsis). Does not cross placenta, so an elevation of IgM in the newborn indicates an intrauterine infection such as rubella, cytomegalovirus, or an STD

Question 28

What is IgA?

Answer 28

about 15% of the immunoglobulins. Mainly present in secretions of respiratory and GI tract, in saliva, in colostrum and in tears and is also in small quantities in the blood

Question 29

What is IgE?

Answer 29

mediates an allergic response and is measured to detect allergic diseases

Question 30

What is IgD?

Answer 30

smallest portion of the immunoglobulins and is rarely evaluated or detected

Question 31

What are the Interfering Factors of Immunoglobin Electrophoresis?

Answer 31

drugs that increase immunoglobulin levels include hydralazine, isoniazid, methadone, oral contraceptives, phenytoin, procainamide, steroids, tetanus toxoid and antitoxin, and therapeutic gamma globulin

Question 32

What causes increased IgA levels?

Answer 32

Chronic liver diseases (primary biliary cirrhosis)

Chronic infections

Inflammatory bowel disease

Question 33

What causes Decreased IgA levels?

Answer 33

Ataxia, telangiectasia, congenital isolated deficiency – diseases caused by isolated IgA or combined immunoglobulin deficiencies.

Hypoproteinemia (nephrotic syndrome, protein losing enteropathies) – causes IgA deficiency.

Drug immunosuppression (steroids, dextran) – IgA production is diminished

Question 34

What causes increased IgG levels?

Answer 34

Chronic granulomatous infections (tuberculosis, Wegener granulomatosis, sarcoidosis), hyperimmunization reactions, chronic liver disease, multiple myeloma (monoclonal IgG type), autoimmune diseases (rheumatoid arthritis, Sjogren disease, systemic lupus erythematosus) – all stimulate IgG synthesis.

Intrauterine devices – localized inflammatory reaction harmful to sperm – causes synthesis of IgG

Question 35

What causes Decreaased IgG levels?

Answer 35

Wiskott-Aldrich syndrome, agammaglobulinemia – genetic deficiency results in decreased synthesis of IgG.
Acquired immunodeficiency syndrome – deficiency throughout the entire immune system.
Hypoproteinemia – causes IgG deficiency.
Drug immunosuppression (steroids, dextran) – production decreased .
Non-IgG multiple myeloma, leukemia – production decreased due to bone marrow taken over by tumor cells

Question 36

What causes increased IgM levels?

Answer 36

Waldenstrom macroglobulinemia – IgM secreted at high levels by malignant lymphoblastic cells.
Chronic infections (hepatitis, mononucleosis, sarcoidosis) – infections stimulate increased production.
Autoimmune diseases (SLE, rheumatoid arthritis).
*Acute infections – IgM is first immunoglobulin to respond to an infection (viral, bacterial, parasitic).
Chronic liver disorders (biliary cirrhosis)

Question 37

What causes Decreased IgM levels?

Answer 37

Agammaglobulinemia – genetic deficiency with inadequate synthesis.
AIDS – deficiency throughout entire immune system.
Hypoproteinemia – decreased protein causes IgM deficiency.
Drug immunosuppression (steroids, dextran) – diminished IgM production
IgG or IgA multiple myeloma, leukemia – production diminished as marrow is taken over by tumor cells

Question 38

What causes Increased IgE levels?

Answer 38

Allergy reactions (hay fever, asthma, eczema, anaphylaxis) – allergic reactions stimulate production of IgE antibodies.

Allergic infections (aspergillosis, parasites)

Question 39

What causes Decreased IgE levels?

Answer 39

Agammaglobulinemia – deficient production of one or all immunoglobulins