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Iron Studies (Iron, TIBC, Transferrin Saturation)

Anemia
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Evaluate causes of fatigue, pallor, hair loss, or restless leg syndrome

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Iron Studies (Iron, TIBC, Transferrin Saturation)

  • Why is it done?
    • Tests measure iron levels in blood and iron transport capacity to assess iron metabolism and detect iron-related disorders
    • Diagnose iron deficiency anemia (low iron levels causing reduced oxygen-carrying capacity)
    • Detect iron overload conditions such as hemochromatosis and secondary iron overload disorders
    • Evaluate anemia of unclear etiology or persistent fatigue, weakness, and shortness of breath
    • Monitor patients with chronic kidney disease, rheumatoid arthritis, or malabsorption syndromes
    • Screen for hereditary hemochromatosis, particularly in patients with family history or elevated liver enzymes
    • Assess efficacy of iron supplementation or phlebotomy therapy in patients undergoing treatment
    • Evaluate inflammation or chronic disease affecting iron metabolism
  • Normal Range
    • Serum Iron: 60-170 mcg/dL (10.7-30.4 mcmol/L) for males; 50-150 mcg/dL (8.9-26.9 mcmol/L) for females. Values vary by laboratory and can fluctuate throughout the day.
    • Total Iron-Binding Capacity (TIBC): 250-450 mcg/dL (45-81 mcmol/L). Reflects total transferrin available to bind and transport iron.
    • Transferrin Saturation: 20-50%. Calculated as (serum iron ÷ TIBC) × 100. Represents percentage of transferrin binding sites occupied by iron.
    • Interpretation Guide:
    • Normal: All three parameters within reference ranges indicate adequate iron stores and appropriate iron metabolism
    • Low iron with elevated TIBC and low transferrin saturation: Indicative of iron deficiency
    • High iron with low or normal TIBC and elevated transferrin saturation: Suggests iron overload
    • Low iron with low TIBC: May indicate inflammation, chronic disease, or liver dysfunction
  • Interpretation
    • Iron Deficiency Anemia: Characterized by low serum iron (<60 mcg/dL), elevated TIBC (>450 mcg/dL), and low transferrin saturation (<20%). Indicates insufficient iron for hemoglobin production.
    • Iron Overload (Hemochromatosis): Marked by elevated serum iron (>170 mcg/dL), low or normal TIBC (<250 mcg/dL), and elevated transferrin saturation (>50-60%). Can lead to organ damage if untreated.
    • Anemia of Chronic Disease: Shows low serum iron, low TIBC, and variable transferrin saturation. Associated with chronic infections, malignancies, autoimmune disorders, or kidney disease.
    • Secondary Iron Overload: Results from repeated transfusions or hemolysis. Shows elevated iron and low TIBC similar to primary hemochromatosis.
    • Factors Affecting Results:
    • Diurnal variation: Serum iron can vary by 20-40% throughout the day (higher in morning)
    • Inflammation: Elevates hepcidin, reducing serum iron and TIBC in acute phase response
    • Medications: Estrogen increases iron; NSAIDs may cause GI bleeding and iron loss; oral contraceptives elevate transferrin
    • Recent transfusions: Artificially elevate serum iron levels for 24-48 hours
    • Time of collection: Morning fasting samples preferred for consistency and reproducibility
    • Clinical Significance:
    • Pattern recognition: Combined interpretation of all three parameters provides diagnostic clarity better than individual values
    • Transferrin saturation >45% warrants investigation for hemochromatosis even if serum iron is borderline
    • Repeated low iron studies differentiate true deficiency from acute inflammation-related changes
  • Associated Organs
    • Primary Organs Involved:
    • Bone marrow: Site of red blood cell production; iron deficiency impairs hemoglobin synthesis, resulting in microcytic anemia
    • Liver: Primary organ for iron storage, metabolism, and hepcidin production; iron overload causes cirrhosis, fibrosis, and hepatocellular carcinoma
    • Heart: Excess iron causes restrictive or dilated cardiomyopathy and conduction abnormalities
    • Pancreas: Iron deposition causes diabetes mellitus and pancreatic insufficiency
    • Pituitary gland: Iron accumulation impairs hormone production affecting growth and reproductive function
    • Gastrointestinal tract: Absorbs iron; disorders affecting absorption cause deficiency; genetic mutations in iron transport genes affect levels
    • Associated Medical Conditions:
    • Hereditary hemochromatosis (HFE mutations): Most common cause of iron overload in Caucasians; progressive organ damage if untreated
    • Thalassemia major: Chronic hemolysis and transfusion requirements lead to secondary iron overload
    • Sickle cell disease: Hemolysis and transfusions cause secondary hemochromatosis
    • Celiac disease: Malabsorption leads to iron deficiency despite adequate intake
    • Chronic kidney disease: Reduced erythropoietin production and iron loss during dialysis cause deficiency
    • Inflammatory bowel disease: Chronic bleeding and malabsorption cause iron deficiency
    • Pregnancy and postpartum: Increased iron demands and blood loss during delivery increase deficiency risk
    • Chronic liver disease: Impaired iron metabolism and cirrhosis risk with overload
    • Potential Complications of Abnormal Results:
    • Iron deficiency: Fatigue, dyspnea, impaired cognition in children, increased infection risk, restless leg syndrome
    • Iron overload: Hepatic cirrhosis, hepatocellular carcinoma, cardiac arrhythmias, heart failure, diabetes mellitus, joint arthropathy, hypogonadism
    • Oxidative stress: Both deficiency and excess impair normal cellular function through reactive oxygen species generation
  • Follow-up Tests
    • Based on Low Iron/Iron Deficiency:
    • Ferritin levels: Marker of iron stores; low levels confirm iron deficiency (typically <30 ng/mL; <10 ng/mL highly specific for deficiency)
    • Complete blood count (CBC): Reveals degree of anemia, RBC indices (microcytic hypochromic pattern in iron deficiency)
    • Reticulocyte count: Assesses bone marrow response to iron supplementation; rising levels indicate effective treatment
    • Soluble transferrin receptor (sTfR): More specific for iron deficiency; rises as storage iron depletes; helps differentiate from anemia of chronic disease
    • Peripheral blood smear: Visualizes RBC morphology; shows microcytic hypochromic cells in deficiency
    • Gastrointestinal evaluation: Upper and lower endoscopy if cause of deficiency unclear; investigate for bleeding or malabsorption
    • Celiac serology: Tissue transglutaminase (tTG-IgA) and endomysial antibodies to screen for malabsorption
    • Based on High Iron/Iron Overload:
    • Ferritin levels: Elevated ferritin (>300 ng/mL males, >200 ng/mL females) indicates iron storage increase; requires further investigation
    • Genetic testing: HFE gene mutations (C282Y and H63D) for hereditary hemochromatosis diagnosis
    • Liver function tests: AST, ALT, bilirubin, albumin to assess hepatic iron-related damage and cirrhosis
    • MRI imaging: Cardiac MRI (T2*) and hepatic iron quantification to assess organ iron deposition and risk
    • Echocardiography: Evaluates cardiac function in iron overload; screens for cardiomyopathy and arrhythmias
    • Glucose screening: Fasting glucose and HbA1c for iron-induced diabetes mellitus
    • Liver ultrasound or elastography: Assesses cirrhosis and portal hypertension development
    • Monitoring During Treatment:
    • Iron studies: Repeat every 4-12 weeks during iron supplementation to assess response and prevent overtreatment
    • Ferritin and transferrin saturation: Monthly monitoring during phlebotomy for hemochromatosis to maintain therapeutic target ranges
    • CBC and reticulocyte count: Assess treatment efficacy and anemia resolution
    • Liver function tests: Every 6-12 months in iron overload conditions to monitor for progressive damage
  • Fasting Required?
    • Fasting Status: YES - Fasting is required for accurate results
    • Duration: 8-12 hours overnight fasting before blood collection recommended
    • Special Instructions:
    • Morning collection preferred: Blood should be drawn in early morning (7-9 AM) to minimize diurnal variation in iron levels
    • Nothing by mouth: No food or beverages except water for 8-12 hours before test; high-carbohydrate meals can affect iron absorption and measurements
    • Consistent timing: Collect tests at same time of day on repeat draws for reliability in monitoring treatment
    • Medications to Avoid or Disclose:
    • Iron supplements: Hold iron supplementation for 24 hours before test to obtain baseline levels; inform laboratory if taking supplements
    • Oral contraceptives: Increase transferrin and may elevate iron; continue as prescribed but notify laboratory
    • Estrogen therapy: May elevate serum iron; disclose use to interpreting physician
    • NSAIDs: May cause GI bleeding affecting results; continue if medically necessary but report to physician
    • Tetracyclines and quinolones: Decrease iron absorption; space 2 hours from iron-containing foods/supplements
    • Proton pump inhibitors: Reduce gastric acid and iron absorption; continue as prescribed and report to lab
    • Additional Patient Preparation:
    • Minimize stress: Avoid strenuous exercise 24 hours before test; physical stress can cause temporary iron fluctuations
    • Avoid caffeine: Caffeine affects iron absorption; abstain for several hours before test
    • Adequate hydration: Drink water throughout the fasting period; dehydration concentrates serum iron artificially
    • Recent transfusions: Disclose within past 48 hours; blood transfusions artificially elevate iron levels
    • Report recent illness: Fever and acute infection affect iron studies; schedule test 1-2 weeks after acute illness resolution

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