UIBC - Kresser Institute Membership Site

Marker Name: UIBC

REFERENCE RANGES FOR TIBC:

Laboratory and functional reference range: 175–350 µg/dL

DESCRIPTION:

Unsaturated iron-binding capacity (UIBC) measures how much additional iron the blood could potentially carry.¹ Since transferrin carries the majority of circulating iron, UIBC represents the approximate concentration of apotransferrin, or transferrin not bound by iron.² UIBC can be measured directly. However, it is typically calculated from total iron-binding capacity (TIBC), which is an indirect estimate of transferrin concentration, and serum iron concentration (SI) using the following formula:^1,3

uibc

Since UIBC varies with TIBC and SI, it is affected by the same health variables; these include iron homeostasis, nutritional status, inflammation, liver function, pregnancy, certain genetic conditions, and certain drugs. For a discussion of how these factors influence serum transferrin and serum iron concentrations, see TIBC and iron reference sheets.

High UIBC can be caused by iron deficiency, pregnancy, states of increased red blood cell production, and certain drugs (e.g., oral contraceptives, proton pump inhibitors, and tetracycline antibiotics).^4-12 A complete list of conditions and drugs that can cause high UIBC is provided below.

Low UIBC can be caused by hereditary hemochromatosis, hereditary atransferrinemia, multiple infusions of iron-containing agents, massive increase in oral iron intake, hypoproteinemia, chronic liver disease, and some cases of chronic inflammation, pernicious anemia, ineffective erythropoiesis, hemolytic anemia, and hemosiderosis.^13-24 A full list of conditions that can cause low UIBC is below.

Since several factors can simultaneously influence UIBC, the test is not conclusive on its own. UIBC should be considered with related iron markers, including a complete blood count (CBC), serum iron, ferritin, TIBC, and iron saturation.¹³

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^4,5

Iron deficiency
- Inadequate dietary intake
  - Diet low in meat
- Gastrointestinal malabsorption
  - Achlorhydria or hypochlorhydria
  - Gastritis
    - Atrophic gastritis
    - Autoimmune metaplastic atrophic gastritis
    - Helicobacter pylori gastritis⁶
  - Celiac disease
  - Post-gastric bypass surgery⁷
- Blood loss⁸
  - Obvious bleeding
    - External wound
    - Melena
    - Hematemesis
    - Hemoptysis
    - Gross hematuria
  - Heavy menstrual bleeding
  - Gastrointestinal bleeding (e.g., hemorrhoids, fissures)
  - Repeated blood donations
  - Surgery
  - Hemodialysis
  - Intraluminal neoplasms (e.g., malignancies of the gastrointestinal tract)⁹
  - Lasthénie de Ferjol syndrome
- Normal pregnancy (in the absence of iron deficiency)⁴
- States of increased red blood cell production
  - Treatment with erythropoietin (EPO)¹⁰
  - Polycythemia vera¹¹
- Drugs¹²
  - Oral contraceptives⁴
  - Proton pump inhibitors
  - H₂ receptor blockers
  - Certain antibiotics (e.g., quinolones, tetracycline)
  - Excessive calcium supplementation

Low in:^13-15

Hereditary hemochromatosis (HH)^16-18
- Human hemochromatosis protein (HFE)-related
  - C282Y homozygosity
  - C282Y/H63D compound heterozygosity
  - Other mutations of HFE
- Other genetic mutation
  - Juvenile hemochromatosis (mutations in hemojuvelin or hepcidin)
  - Ferroportin mutations
  - Transferrin receptor 2 mutation (rare)
- Hereditary atransferrinemia
- Multiple infusions of iron-containing agents
  - Red cell transfusion
  - Multiple infusions of intravenous iron
  - Intravenous hemin/hematin
- Massive increase in oral iron intake
  - High-dose iron supplementation
  - Medications containing iron
  - Diet
- Hypoproteinemia, as seen in:
  - Malnutrition (e.g., kwashiorkor)
  - Nephrotic syndrome
- Chronic liver disease
  - Hepatitis B or C
  - Alcohol-induced liver disease
  - Porphyria cutanea tarda
  - Steatohepatitis (fatty liver disease)
  - Neonatal or perinatal iron overload, due to gestational alloimmune liver disease¹⁹
- Chronic inflammation (can be low, but sometimes normal)²⁰
  - Multiple causes (e.g., chronic infection, malignancy, rheumatologic disorders, inflammatory bowel disease, acute and chronic immune activation, etc.)
- Pernicious anemia (can be low, but sometimes normal)²¹
- Ineffective erythropoiesis (can be low, but sometimes normal)
  - Hereditary sideroblastic anemias²²
  - Severe alpha and beta thalassemia²³
  - Myelodysplastic syndrome (MDS) variants, such as refractory anemia with ringed sideroblasts (RARS)²⁴
- Hemolytic anemia (can be low, but sometimes normal), such as:
  - Autoimmune hemolytic anemia
  - Sickle cell anemia
- Hemosiderosis (can be low, but sometimes normal)
  - Pulmonary hemosiderosis (as seen in anti-glomerular basement membrane antibody disease)
  - Chronic hemolysis

FUNCTIONAL RANGE INDICATIONS:

High in:

Functional iron deficiency
Pregnancy

Low in:

Functional iron overload
Functional liver problems
Chronic inflammation

References: