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Introduction to Iron Metabolism and Laboratory Indicators: Iron, Transferrin, TIBC, and Ferritin

Introduction

Iron is one of the essential elements in the human body and plays a critical role in hemoglobin synthesis, oxygen transport, cellular energy production, and numerous enzymatic reactions. An adult human body contains approximately 3–4 grams of iron, most of which is found in the hemoglobin of red blood cells, muscle myoglobin, and cellular enzymes. Only a small fraction of iron circulates in the bloodstream, where it is transported by a protein called Transferrin.

The human body does not have an active mechanism for iron excretion; therefore, iron balance is primarily regulated through its absorption in the small intestine. A hormone called Hepcidin, which is produced in the liver, is the main regulator of iron metabolism. Increased hepcidin levels reduce iron absorption and decrease the release of iron from body stores, whereas reduced hepcidin levels enhance iron absorption and mobilization from storage sites.

Assessment of the body’s iron status cannot be achieved by measuring Serum Iron alone. For an accurate interpretation of iron metabolism, the results of Serum Iron, Transferrin, Total Iron Binding Capacity (TIBC), Ferritin, and in many cases Transferrin Saturation (TSAT) are evaluated simultaneously.

 

1) Serum Iron

Definition

Serum Iron represents the amount of iron bound to the Transferrin protein in the bloodstream. This test reflects the amount of iron currently being transported in circulation and does not represent the actual iron stores of the body.

Since serum iron concentration is influenced by factors such as dietary intake, time of blood collection, inflammation, and various physiological conditions, it should always be interpreted together with other iron metabolism indicators.

Clinical Applications

Measurement of Serum Iron is used in the following conditions:

·         Evaluation of iron deficiency

·         Assessment of different types of anemia

·         Detection of Iron Overload

·         Evaluation of Hemochromatosis

·         Monitoring the response to iron supplementation therapy

·         Investigation of disorders related to iron metabolism

 

Causes of Decreased Serum Iron

A decrease in Serum Iron may be observed in the following conditions:

·         Iron deficiency

·         Chronic blood loss

·         Pregnancy

·         Malnutrition

·         Malabsorption (such as celiac disease)

·         Chronic inflammatory diseases

·         Acute and chronic infections

·         Renal failure

·         Certain malignancies

 

Causes of Increased Serum Iron

An increase in Serum Iron may be observed in the following conditions:

·         Primary hemochromatosis

·         Repeated blood transfusions

·         Excessive intake of iron supplements

·         Hemolysis

·         Hepatitis and liver diseases

·         Sideroblastic anemia

·         Beta-thalassemia major

 

Important Points in the Interpretation of Serum Iron

·         Serum Iron exhibits diurnal variation and is usually highest during the early morning hours.

·         Fasting blood sampling may improve the accuracy of test results.

·         Taking iron supplements before blood collection may cause falsely elevated results.

·         Hemolysis of the sample can lead to a falsely increased Serum Iron level.

·         Due to daily fluctuations, interpretation of Serum Iron alone is not recommended; it should be evaluated together with Ferritin, TIBC, and Transferrin.

 

Transferrin

Definition

Transferrin is a glycoprotein that is primarily synthesized in the liver, and its main function is to transport iron in the bloodstream. Each transferrin molecule can bind two ferric iron ions (Fe³⁺) and transport them to tissues such as the bone marrow, liver, and other organs.

Under normal conditions, approximately 20–45% of transferrin binding sites are occupied by iron, while the remaining capacity is available for binding additional iron.

Clinical Importance

Measurement of Transferrin helps physicians evaluate the status of iron transport in the body. This parameter is particularly important in the differential diagnosis of various types of anemia, as well as in the evaluation of liver diseases, malnutrition, and disorders of iron metabolism.

Conditions Associated with Increased Transferrin

Transferrin levels are usually increased in the following conditions:

·         Iron deficiency

·         Pregnancy

·         Estrogen therapy or use of oral contraceptive pills

·         Chronic blood loss

·         Early stages of iron deficiency

In these conditions, the body increases transferrin production to enhance iron binding, absorption, and transport.

Conditions Associated with Decreased Transferrin

A decrease in Transferrin may be observed in the following conditions:

·         Chronic inflammatory diseases

·         Severe liver diseases

·         Malnutrition

·         Nephrotic syndrome

·         Hemochromatosis

·         Malignancies (cancers)

 

Total Iron Binding Capacity (TIBC)

Definition

TIBC (Total Iron Binding Capacity) represents the maximum capacity of the Transferrin protein to bind iron.

Since almost all iron-binding capacity in serum is related to Transferrin, the TIBC value indirectly reflects the amount of transferrin present in the blood.

Therefore:

·         Increased TIBC usually indicates increased Transferrin levels.

·         Decreased TIBC usually indicates decreased Transferrin levels.

 

Clinical Applications

Measurement of TIBC, along with Iron and Ferritin, provides valuable information about the body’s iron storage status and is used in the diagnosis and evaluation of the following conditions:

·         Iron deficiency

·         Iron overload

·         Chronic diseases

·         Liver diseases

·         Malnutrition

 

Conditions Associated with Increased TIBC

TIBC levels may increase in the following conditions:

·         Iron deficiency

·         Pregnancy

·         Estrogen therapy

·         Chronic blood loss

 

Conditions Associated with Decreased TIBC

TIBC levels may decrease in the following conditions:

·         Chronic inflammatory diseases

·         Hemochromatosis

·         Liver diseases

·         Severe malnutrition

·         Nephrotic syndrome

Unsaturated Iron Binding Capacity (UIBC)

Definition

UIBC (Unsaturated Iron Binding Capacity) represents the portion of Transferrin iron-binding capacity that is not yet occupied by iron.

In other words, UIBC indicates the available or unoccupied binding capacity of Transferrin for additional iron binding.

The relationship between these parameters is as follows:

TIBC = Serum Iron + UIBC

 

Interpretation

In Iron Deficiency:

·         Iron ↓

·         UIBC ↑

·         TIBC ↑

In Iron Overload:

·         Iron ↑

·         UIBC ↓

·         TIBC ↓ or Normal

 

Ferritin

Definition

Ferritin is the most important iron-storage protein in the body and is mainly found in the liver, spleen, bone marrow, and muscles.

Serum ferritin concentration is considered the best indicator for evaluating the body’s iron stores.

Clinical Importance

Measurement of Ferritin is one of the most sensitive tests for detecting iron deficiency. A decrease in ferritin levels can usually be detected before a reduction in hemoglobin occurs.

Important Note

Unlike Serum Iron, Ferritin is an Acute Phase Reactant.

Therefore, ferritin levels may increase in response to inflammation, infection, and chronic diseases, even when the body’s iron stores are low. For this reason, ferritin should always be interpreted together with other iron parameters such as Serum Iron, TIBC, Transferrin, and Transferrin Saturation (TSAT).

Therefore, Ferritin may increase in the following conditions without the presence of iron overload:

·         Infection

·         Inflammation

·         Autoimmune diseases

·         Cancers (malignancies)

·         Liver diseases

·         Kidney failure

For this reason, a normal or elevated Ferritin level does not always indicate adequate iron stores.

 

Conditions Associated with Decreased Ferritin

Ferritin levels may decrease in the following conditions:

·         Iron deficiency

·         Malnutrition

·         Chronic blood loss

·         Pregnancy

 

Conditions Associated with Increased Ferritin

Ferritin levels may increase in the following conditions:

·         Inflammation

·         Infection

·         Liver diseases

·         Hemochromatosis

·         Repeated blood transfusions

·         Beta-thalassemia major

·         Certain malignancies

 

Transferrin Saturation (TSAT)

Definition

Transferrin Saturation (TSAT) represents the percentage of Transferrin iron-binding capacity that is occupied by iron.

It indicates how much of the available transferrin binding sites are currently filled with iron.

Calculation Formula:

TSAT (%) = (Serum Iron ÷ TIBC) × 100

Reference Range

The normal range of TSAT in adults is generally 20–45%.

 

Interpretation

TSAT Less Than 20%

Suggestive of:

·         Iron deficiency

·         Iron deficiency anemia

·         Some chronic diseases

 

TSAT Greater Than 45%

Suggestive of:

·         Hemochromatosis

·         Iron overload

·         Excessive iron intake

·         Repeated blood transfusions

 

Important Sample Collection Considerations

·         The sample should preferably be collected in the morning and in a fasting state.

·         Taking iron supplements within 24 hours before blood collection (according to the physician’s recommendation) may affect test results.

·         Hemolysis of the sample can cause a falsely elevated Iron level.

·         Recent blood transfusions may increase Iron and Ferritin levels.

·         Test results should always be interpreted together with the patient’s clinical history, CBC results, and other iron metabolism indicators.

 

Overall Interpretation of Iron Profile Parameters

Disease / Condition	Serum Iron	TIBC	Ferritin	Transferrin Saturation (TSAT)	Hemoglobin (Hb)
Iron Deficiency Anemia	↓ Low	↑ High	↓ Low	↓ Low (usually <15%)	↓ Low
Anemia of Chronic Disease	↓ Low	↓ Low or Normal	Normal or ↑ High	↓ Low or Normal	↓ Low
Hemochromatosis	↑ High	↓ Low	↑↑ Very High	↑ High (usually >45%)	Normal or ↑ High
Thalassemia Minor	Normal	Normal	Normal	Normal  (approximately 20-50%)	Slightly decreased or below normal
Thalassemia Major (with regular blood transfusions)	↑↑ Very High	Low or Normal	↑↑ Very High (often >1000)	↑ High (usually >80%)	Without transfusion: severely decreased
Sideroblastic Anemia	↑ High	Normal	Normal or ↑ High	↑ High	↓ Low

 

Effects of Medications on Iron Metabolism Indicators

Many medications and supplements can alter Serum Iron, TIBC, and Ferritin levels. These changes may sometimes provide important diagnostic clues, while in other cases they should be considered when interpreting laboratory results.

 

SGLT2 Inhibitors

(such as Canagliflozin and Empagliflozin)

·         May decrease Ferritin by approximately 11.5%

·         May increase TIBC by approximately 2.1%

 

HIF-Prolyl Hydroxylase Inhibitors (HIF-PH inhibitors)

(such as Roxadustat)

By increasing red blood cell production and enhancing iron utilization:

·         Increase iron consumption

·         May lead to a decrease in Ferritin

·         May decrease TIBC

 

Pentoxifylline (PTX)

By reducing Hepcidin (the hormone responsible for regulating iron metabolism):

·         Improves iron availability

·         Enhances iron utilization

 

Antioxidant Supplements

(such as Silymarin, Green Tea, and Grape Seed Extract)

Have been associated with:

·         Decreased Ferritin

·         Increased TIBC

 

Anti-inflammatory Drug: Tocilizumab

By reducing inflammatory activity:

·         Reduces the effects of inflammation on iron metabolism

·         May increase TIBC

 

Iron Supplements (Oral and Intravenous)

·         Directly increase Ferritin levels

·         Increase available iron stores

 

Lactoferrin Supplements

May cause significant increases in:

·         Ferritin

·         Serum Iron

·         Transferrin Saturation (TSAT)

 

Note: The interpretation of iron profile results should always be performed considering the patient’s clinical condition, inflammatory status, kidney and liver function, CBC parameters, and medication history.

 

Treatment of Iron Deficiency and Evaluation of Laboratory Changes After Therapy

1. Medications Used in Iron Deficiency

Treatment of iron deficiency is generally aimed at replenishing body iron stores, increasing hemoglobin production, and correcting anemia.

 

A) Oral Iron Supplements

Oral iron therapy is considered the first-line treatment in most patients.

 

1. Ferrous Sulfate

Ferrous Sulfate is one of the most commonly used iron preparations.

Mechanism of Action:

Provides ferrous iron ions (Fe²⁺)
Increases intestinal iron absorption
Enhances hemoglobin synthesis
Laboratory Effects After Treatment:

Parameter	Change After Treatment
Hemoglobin (Hb)	↑ Increased
Hematocrit (Hct)	↑ Increased
MCV	↑ Increased (correction of microcytosis)
MCH	↑ Increased
RDW	May initially ↑ then decrease
Serum Iron	↑ Increased
Ferritin	↑ Increased
TIBC	↓ Gradual decrease
Transferrin	↓ Gradual decrease
TSAT	↑ Increased

2. Ferrous Fumarate

Ferrous Fumarate contains a higher percentage of elemental iron compared with some other oral iron preparations.

Applications:

Iron deficiency anemia
Pregnancy
Chronic blood loss

3. Ferrous Gluconate

Ferrous Gluconate generally has better gastrointestinal tolerance.

Suitable For:

Patients who experience nausea, abdominal pain, or constipation with Ferrous Sulfate
 

B) Intravenous Iron

Intravenous iron therapy is used when:

Oral iron absorption is inadequate
The patient cannot tolerate oral iron
Rapid correction of iron deficiency is required
 

1. Iron Sucrose

Applications:

Chronic kidney disease
Dialysis patients
Severe iron deficiency
 

2. Ferric Carboxymaltose

Advantage:

Allows administration of a higher iron dose in a single session
 

3. Iron Dextran

Used in:

Severe iron deficiency
Conditions requiring replacement of a large amount of iron
 

Note: After initiation of iron therapy, laboratory changes occur gradually. Typically, reticulocyte count increases first, followed by improvement in hemoglobin, while restoration of ferritin (iron stores) usually requires a longer treatment period. The response to treatment should be monitored using CBC, Ferritin, Serum Iron, TIBC, and TSAT together.

Effects of Iron Therapy on CBC Parameters

1. Hemoglobin (Hb)

Hemoglobin is the most important indicator of therapeutic response.

After successful initiation of iron therapy:

An increase of approximately 1–2 g/dL in Hb within 2–4 weeks is expected.

 

2. Hematocrit (Hct)

Hematocrit increases as the number of red blood cells increases.

 

3. Mean Corpuscular Volume (MCV)

In iron deficiency anemia, MCV is usually decreased:

Iron deficiency → ↓ MCV

After treatment:

→ MCV gradually increases toward the normal range

However, because the lifespan of red blood cells is approximately 120 days, complete correction of MCV may take several months.

 

4. Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC)

In iron deficiency:

MCH ↓
MCHC ↓
After treatment:

Increased hemoglobin content inside red blood cells
Improvement of red blood cell pallor (Hypochromia correction)
 

5. Red Cell Distribution Width (RDW)

In iron deficiency, RDW is usually increased:

Iron deficiency → ↑ RDW

During the early stages of treatment, RDW may temporarily increase because:

Older red blood cells remain small in size
Newly produced red blood cells are more normal in size
Over time, RDW gradually returns toward the normal range as the red blood cell population becomes more uniform.

 

Effects of Iron Therapy on Iron Panel Parameters

Serum Iron

Before Treatment:

↓ Decreased

After Treatment:

↑ Increased

However, due to daily fluctuations and biological variability, Serum Iron alone is not a reliable indicator for monitoring treatment response.

Evaluation should be performed together with:

Ferritin
TIBC
Transferrin
TSAT
 

Ferritin

Ferritin is the most important indicator of the restoration of body iron stores.

Before Treatment:

↓ Low

After Treatment:

↑ Gradual increase

Treatment should usually be continued even after correction of Hemoglobin (Hb) levels to allow complete replenishment of iron stores.

 

TIBC (Total Iron Binding Capacity)

In iron deficiency:

↑ Increased

After treatment:

↓ Decreases toward the normal range

This occurs because the body no longer needs to produce excessive amounts of Transferrin.

 

Transferrin

Before Treatment:

↑ Increased

After Treatment:

↓ Decreased

 

UIBC (Unsaturated Iron Binding Capacity)

Before Treatment:

↑ Increased

After Treatment:

↓ Decreased

TSAT (Transferrin Saturation)

Before Treatment:

↓ Below the normal range

After Treatment:

↑ Increased

 

Medications That May Cause Decreased Iron Levels

Some medications can reduce iron absorption:

Medication
Mechanism
Proton Pump Inhibitors

 (Omeprazole, Pantoprazole)
Reduce gastric acid production and decrease iron absorption
Antacids
Decrease iron absorption
Calcium Supplements
Compete with iron absorption
Some Antibiotics (Tetracyclines, Quinolones)
Bind to iron and reduce absorption
Cholestyramine
Decreases iron absorption
 

Medications and Conditions That Increase Iron Requirements or Risk of Deficiency

Medication / Condition
Effect
Erythropoietin
Increases iron utilization for red blood cell production
Anticoagulants (Warfarin, Heparin)
Increase the risk of bleeding
NSAIDs (such as Ibuprofen)
May cause gastrointestinal bleeding
 

Summary of Laboratory Changes After Successful Iron Therapy

Parameter
Before Treatment

(Iron Deficiency)
After Successful Treatment
Hb
↓ Decreased
↑ Increased
Hct
↓ Decreased
↑ Increased
MCV
↓ Decreased
↑ Increased
MCH
↓ Decreased
↑ Increased
RDW
↑ Increased
↓ Decreased
Ferritin
↓ Decreased
↑ Increased
Iron
↓ Decreased
↑ Increased
TIBC
↑ Increased
↓ Decreased
UIBC
↑ Increased
↓ Decreased
Transferrin
↑ Increased
↓ Decreased
TSAT
↓ Decreased
↑ Increased
 

 

Causes of Increased or Decreased TIBC and the Effect of Treating Underlying Diseases on Iron Metabolism Parameters

TIBC (Total Iron Binding Capacity) represents the iron-binding capacity of Transferrin. An increase or decrease in TIBC is usually an indicator of an underlying physiological or pathological condition.

Therefore, treatment is directed toward the underlying cause of abnormal TIBC levels.

 

Low TIBC

Definition

A decreased TIBC indicates that the amount of Transferrin or the iron-carrying capacity of the blood is reduced.

Since Transferrin is produced in the liver, decreased TIBC is commonly observed in conditions such as:

Chronic inflammation
Liver diseases
Malnutrition
Kidney diseases
Chronic infections
Malignancies
 

1. Anemia of Chronic Disease (ACD)

One of the most common causes of low TIBC is Anemia of Chronic Disease.

Mechanism:

Inflammation increases the level of the hormone Hepcidin.
Hepcidin prevents the release of iron from body storage sites.
Iron remains stored inside cells but is unavailable for red blood cell (RBC) production.
 

Laboratory Pattern:

Parameter
Change
Iron
↓ Decreased
Ferritin
↑ Increased or Normal
TIBC
↓ Decreased
Transferrin
↓ Decreased
TSAT
↓ Decreased

Treatment

Treatment focuses on controlling the underlying disease.

Anti-inflammatory or disease-controlling medications:

Corticosteroids (in some inflammatory diseases)
Biologic drugs in autoimmune diseases
Antibiotics in chronic infections
 

Effect on Blood Tests

With control of inflammation:

Parameter
Change
Hb
↑ Increased
Iron
↑ Increased
TIBC
↑ Returns toward normal
Ferritin
↓ Decreased
CRP
↓ Decreased
ESR
↓ Decreased
 

2. Liver Disease

Since Transferrin production occurs in the liver, liver damage can cause a reduction in transferrin levels.

Causes:

Cirrhosis
Hepatitis
Liver failure
 

Treatment

Depending on the cause:

Treatment of hepatitis
Removal of liver-damaging factors
Treatment of the underlying disease
Correction of malnutrition
 

 

Effect on Laboratory Tests

With improvement in liver function:

Parameter
Change
Transferrin
↑ Increased
TIBC
↑ Increased
Albumin
↑ Increased
Liver enzymes
↓ Decreased
 

3. Malnutrition and Protein Deficiency

Because Transferrin is a protein, reduced protein levels in the body lead to decreased transferrin production.

Causes:

Inadequate protein intake
Malabsorption
Chronic diseases
 

Treatment:

High-protein diet
Nutritional supplements
Treatment of underlying gastrointestinal disorders
 

Laboratory Effects:

Parameter
Change
Transferrin
↑ Increased
TIBC
↑ Increased
Albumin
↑ Increased
Hb
↑ Increased

4. Chronic Kidney Disease (CKD)

In kidney disease:

Erythropoietin production decreases.
Red blood cell production decreases.
Inflammation increases.
Medications Used:

Erythropoiesis Stimulating Agents (ESA)

Examples:

Epoetin alfa
Darbepoetin alfa
Sometimes used together with:

Iron sucrose
Ferric carboxymaltose
 

Effects on Blood Parameters:

Parameter
Change
Hb
↑ Increased
RBC
↑ Increased
Hct
↑ Increased
Iron availability
↑ Increased
 

Medications That May Decrease TIBC

Medication
Effect
Corticosteroids
May decrease TIBC
Androgens
Decrease Transferrin production
Anti-inflammatory drugs
May alter TIBC by reducing inflammation
Chemotherapy drugs
Reduce protein production
 

Does Iron Supplementation Increase TIBC?

No, not directly.

If a person has true iron deficiency, iron supplementation causes:

↑ Ferritin
↑ Serum Iron
↑ TSAT
↑ Hb
However, TIBC usually decreases or returns toward the normal range because the body no longer needs to increase Transferrin production to capture more iron.

 

Ferritin Management and Its Relationship with Iron Metabolism Parameters

Unlike TIBC, there is usually no medication prescribed specifically to increase Ferritin itself. Instead, treatment focuses on correcting the underlying cause of low or high Ferritin levels.

Ferritin represents the body’s iron storage level and is also considered an acute-phase inflammatory marker.

 

1. Low Ferritin

A low Ferritin level usually indicates depleted iron stores and is treated with iron supplementation.

Medications and Their Effects on Laboratory Parameters

Medication
Effect on Laboratory Parameters
Ferrous Sulfate
↑ Ferritin, ↑ Serum Iron, ↑ Hb, ↓ TIBC
Ferrous Fumarate
Increases iron stores and improves anemia
Ferrous Gluconate
Gradual increase in iron levels with fewer gastrointestinal side effects
Iron Polymaltose Complex
Increases stored iron; suitable for some patients who cannot tolerate oral iron
Iron Sucrose / Ferric Carboxymaltose
Rapid increase in Ferritin and Iron levels in severe deficiency or lack of response to oral iron
 

Expected Effects on Iron Panel After Iron Deficiency Treatment

Parameter
Change After Treatment
Ferritin
↑ Increased
Serum Iron
↑ Increased
TIBC
↓ Decreased
Transferrin
↓ Decreased
Hb and Hct
↑ Increased (if anemia is present)
MCV / MCH
↑ Gradual increase
2. High Ferritin

In cases of elevated Ferritin, iron supplementation is usually not recommended. Treatment depends on the underlying cause.

 

A) Iron Overload (e.g., Hemochromatosis)

Medications / Treatments:

Deferoxamine
Deferasirox
Deferiprone
Effects:

↓ Ferritin
↓ Body iron stores
↓ Serum Iron (in some conditions)
In addition, therapeutic phlebotomy (blood removal therapy) may be used to reduce excessive iron accumulation.

 

B) Increased Ferritin Due to Inflammation or Infection

Examples:

Chronic diseases
Infections
Autoimmune diseases
Treatment:

Treatment focuses on the underlying condition:

Antibiotics for infections
Anti-inflammatory medications
Disease-specific therapies
 

Typical Laboratory Pattern in These Conditions:

Parameter
Change
Ferritin
↑ Increased
Serum Iron
↓ Decreased
TIBC
↓ Decreased or Normal
Transferrin
↓ Decreased
 

Important Point for Laboratory Interpretation

Classic Pattern:

Iron Deficiency:

Ferritin ↓
Iron ↓
TIBC ↑
Transferrin ↑
 

 

Inflammation / Chronic Disease:

Ferritin ↑
Iron ↓
TIBC ↓
Transferrin ↓

 

Iron Profile Interpretation Table

Clinical Condition
Serum Iron
TIBC
Ferritin
Transferrin
Possible Interpretation
Iron Deficiency Anemia
↓ Decreased
↑ Increased
↓ Decreased
↑ Increased
Depletion of body iron stores; the most common cause of iron deficiency anemia
Iron Deficiency Treatment with Supplements
↑ Increased
↓ Gradual decrease
↑ Increased
↓ Decreased
Appropriate response to iron therapy
Chronic Disease / Inflammation (Anemia of Chronic Disease)
↓ Decreased
↓ Decreased or Normal
↑ Increased or Normal
↓ Decreased
Iron is present in body stores but its availability for erythropoiesis is reduced
Sideroblastic Anemia
↑ Increased
Normal or ↓ Decreased
↑ Increased
Normal or ↓ Decreased
Impaired utilization of iron for hemoglobin synthesis
Hemochromatosis

 (Iron Overload)
↑ Increased
↓ Decreased
↑↑ Markedly Increased
↓ Decreased
Excessive accumulation of iron in the body
Iron Toxicity
↑↑ Increased
↓ Decreased
↑ Increased
↓ Decreased
Severe increase in serum iron and stored iron
Chronic Blood Loss Anemia
↓ Decreased
↑ Increased
↓ Decreased
↑ Increased
Gradual loss of iron (such as gastrointestinal bleeding or heavy menstrual bleeding)
Acute Inflammation or Infection
↓ Decreased
↓ Decreased
↑ Increased
↓ Decreased
Increased Ferritin due to the inflammatory response
Liver Diseases
↑ or Normal
Variable
↑ Increased
↓ or Normal
Liver damage may cause release of stored Ferritin
Malnutrition or Reduced Protein Synthesis
↓ or Normal
↓ Decreased
↓ or Normal
↓ Decreased
Reduced production of Transferrin in the body
Summary of Changes in Each Parameter

Test
Meaning
Causes of Increase
Causes of Decrease
Serum Iron
Amount of circulating iron in the blood
Iron overload, hemolysis, some liver diseases
Iron deficiency, inflammation, chronic disease
TIBC
Iron-binding capacity of Transferrin
Iron deficiency, chronic blood loss
Inflammation, liver disease, malnutrition
Ferritin
Body iron storage + inflammatory marker
Inflammation, iron overload, liver disease
Depletion of iron stores

 (most important indicator of iron deficiency)
Transferrin
Iron transport protein
Iron deficiency
Inflammation, liver disease, malnutrition