Iron Deficiency: Which Blood Tests Do You Need?

The body holds about 3–4 grams of iron: two-thirds in hemoglobin, most of the rest in storage as ferritin, and a small amount in transit on transferrin. Iron deficiency develops in order. Stores empty first (ferritin falls), then transport iron falls (serum iron and transferrin saturation drop while the empty transferrin — measured as TIBC — rises), and only last does red-cell production run short, producing small, pale cells (low MCV and MCH, high RDW) and finally a low hemoglobin: iron deficiency anemia.

That sequence is why a normal hemoglobin does not exclude the problem. Iron deficiency without anemia is more common than the anemia itself, especially in menstruating women, adolescents, athletes and pregnancy, and it causes fatigue, exercise intolerance, hair shedding, restless legs, poor concentration and cold intolerance on its own. Ferritin is the test that catches it: in a person without inflammation, ferritin below 30 ng/mL means the stores are empty, and below 15 is unequivocal. Many laboratories still print a lower limit of 10–12 ng/mL, which is why so many symptomatic people are told their iron is "normal".

The one complication is that ferritin is also an acute-phase protein: infection, inflammation, obesity, liver disease, kidney disease and cancer raise it regardless of iron stores. With a raised CRP, iron deficiency is still likely with a ferritin below 100 ng/mL and a transferrin saturation below 20%. That is the pattern the panel is built to read.

Ferritin. The storage marker and the diagnostic test. Below 30 ng/mL: iron deficiency. 30–100 with a raised CRP, a low saturation or a convincing picture: probably still deficiency. Above 100 in someone who is not inflamed: iron deficiency is unlikely and another cause of the symptoms or anemia is sought. Ferritin is also the number used to decide when to stop treatment — stores are replete at about 50–100 ng/mL, not when the hemoglobin normalizes.

Serum iron, TIBC and transferrin saturation. Serum iron swings with meals, supplements and the time of day, so it is read only as part of the saturation: iron divided by TIBC. Saturation below 20% (below 16% on stricter definitions) with a high TIBC is the deficiency pattern; low iron with a low TIBC and a normal or high ferritin is the inflammation pattern — iron locked in stores by hepcidin — and iron tablets do little for it. The draw must be morning and fasting, 24 hours off iron.

CBC with differential. Hemoglobin says whether anemia has developed (below 13 g/dL in men, 12 in non-pregnant women, 11 in pregnancy); MCV and MCH say whether the cells are small and pale; RDW rises early because new small cells mix with older normal ones; the platelet count is often mildly raised in iron deficiency. A low MCV with a normal ferritin raises thalassemia trait, which is sorted out with a Mentzer index and hemoglobin electrophoresis rather than iron.

Reticulocyte count. The marrow's output of new red cells. Low in untreated deficiency; a rise within 5–10 days of starting iron is the earliest proof that the diagnosis and the treatment are right, before the hemoglobin has moved.

CRP, celiac serology, B12 and folate. CRP decides which ferritin cutoff applies. Tissue transglutaminase IgA (with a total IgA) is recommended for everyone with iron deficiency anemia because celiac disease is a common, silent cause of malabsorption and is found in 3–5% of them. B12 and folate are checked because a second deficiency hides behind the first, particularly in vegans, after bariatric surgery, and on metformin or acid-suppressing drugs — and because a mixed picture normalizes the MCV and fools the blood count.

• Anyone with the symptoms — fatigue out of proportion to sleep, breathlessness on stairs, palpitations, headaches, hair shedding, brittle or spoon-shaped nails, restless legs, a craving for ice (pagophagia), a sore tongue, cold hands and feet, poor concentration or exercise performance that has fallen off.
• Menstruating women, especially with heavy periods (soaking through protection hourly, clots, periods over seven days): iron deficiency affects one in three, most without anemia.
• Pregnancy and the year after — demand triples; ferritin at the booking visit and in the third trimester is standard in many guidelines.
• Endurance athletes, adolescents in a growth spurt, frequent blood donors, vegetarians and vegans, and anyone on a restricted diet.
• Gut conditions and surgery — celiac disease, Crohn's or ulcerative colitis, bariatric surgery, chronic use of proton-pump inhibitors or antacids, Helicobacter pylori gastritis.
• Heart failure and chronic kidney disease, where iron deficiency is common, worsens symptoms and is treated on its own terms (often with intravenous iron).
• Men and women past menopause with a low ferritin or anemia — not a group to screen, but a group in whom a finding is always investigated: iron deficiency here is bleeding from the gut until proven otherwise.

Preparation. Draw in the morning after an overnight fast and take no iron supplement or multivitamin with iron for 24 hours — a tablet that morning raises serum iron and saturation for hours and can hide deficiency. Avoid testing during an acute infection or within a day or two of hard exercise, both of which raise ferritin and CRP. Menstruation does not affect ferritin meaningfully, so there is no need to time the draw to the cycle.

Ferritin below 30, saturation below 20%, normal hemoglobin: iron deficiency without anemia — treat and find the cause. The same with a low hemoglobin, low MCV and high RDW: iron deficiency anemia. Ferritin 30–100 with a raised CRP and a low saturation: iron deficiency with inflammation — treat the deficiency and the inflammation; intravenous iron is often used because hepcidin blocks oral absorption. Low iron with a low TIBC and a normal or high ferritin: anemia of inflammation, not deficiency — iron tablets will not help. Low MCV with a normal ferritin and saturation: think thalassemia trait. High ferritin with a high saturation: iron overload, the opposite problem.

The diagnosis is only half the job. Iron deficiency is a symptom of something: in a menstruating woman, usually the periods (and a gynecology review when they are heavy); in pregnancy, demand; in a vegan, intake; in anyone with gut symptoms, weight loss or a family history, celiac disease or inflammatory bowel disease; and in men and postmenopausal women, blood loss from the gut — ulcers, aspirin and NSAIDs, polyps, angiodysplasia and colorectal cancer — which is why the AGA recommends endoscopy and colonoscopy for them (and for premenopausal women whose deficiency is not explained by periods), celiac serology for all, and H. pylori testing when the upper endoscopy is normal. A urinalysis catches the uncommon urinary cause.

Follow-up is by numbers too. Hemoglobin should rise by about 1 g/dL within two to four weeks of effective oral iron and normalize by two months; ferritin takes three to six months to rebuild and treatment continues until it is above 50–100 ng/mL. No response by four to six weeks means the iron is not being absorbed, is still being lost, or the diagnosis is wrong — all reasons to go back rather than to keep taking tablets.

Order online, walk into any Quest or Labcorp location with your requisition — no appointment or doctor's visit needed — and results post to your account, most within one to two business days. Morning, fasting, off iron for 24 hours.

Take the results to your clinician. Iron replacement itself — the form, the dose, alternate-day oral dosing that absorbs as well as daily with fewer side effects, or intravenous iron when oral fails or absorption is the problem — is decided with them, and so is the search for the cause, which may need a referral. Black or tarry stools, vomiting blood, breathlessness at rest, chest pain, fainting, or a hemoglobin below about 7–8 g/dL need same-day care rather than a follow-up appointment.