Blood & Lymphoreticular

Iron deficiency anemia: workup and oral vs IV iron

Clinical Overview and When to Suspect Iron Deficiency Anemia

— Menstruating or pregnant patient with fatigue, dyspnea on exertion, pica, restless legs, hair shedding, brittle nails

— Adult >50 (especially male or postmenopausal female) with new microcytic anemia → assume GI blood loss until proven otherwise

— Patient on chronic NSAIDs, anticoagulants, or aspirin

— Bariatric surgery (Roux-en-Y, sleeve), celiac disease, autoimmune atrophic gastritis, H. pylori, IBD

— Vegan/vegetarian diet, infants on cow's milk before age 1, athletes (foot-strike hemolysis, hepcidin from inflammation)

— CKD, heart failure (functional iron deficiency), inflammatory bowel disease

— No routine screening of asymptomatic non-pregnant adults

— Pregnant patients: screen at first prenatal visit with CBC; recheck at 24–28 weeks

— Children: screen once around 12 months (CDC/AAP); risk-based thereafter

Board pearl: In a man or postmenopausal woman with new IDA, the answer is almost always bidirectional endoscopy (EGD + colonoscopy) before chasing menstrual or dietary causes — even if the patient reports heavy NSAID use. Missing colon cancer is the classic Step 3 trap. Document the indication clearly; this is a same-encounter referral, not a "watchful waiting" decision.

Iron deficiency anemia (IDA) is the most common anemia worldwide and the most common cause of microcytic anemia in US adults; on Step 3 it appears in primary care, women's health, GI, and perioperative vignettes.

Core pathophysiology: negative iron balance → depleted storage iron (ferritin falls first) → depleted transport iron (low serum iron, high TIBC) → impaired heme synthesis → microcytic hypochromic RBCs.

When to suspect IDA in ambulatory practice:

Screening (USPSTF):

Symptoms correlate poorly with hemoglobin; check ferritin even when CBC is borderline if pica, fatigue, or restless legs are prominent.

Presentation Patterns and Key History

— Fatigue, exercise intolerance, exertional dyspnea, palpitations, lightheadedness

— Pica (ice = pagophagia is most specific), clay, starch, paper

— Restless legs syndrome — disproportionately common in IDA; check ferritin in any new RLS

— Hair thinning, brittle/spoon nails (koilonychia), angular cheilitis, glossitis, dysphagia (Plummer-Vinson)

— Cold intolerance, headaches, poor concentration; pediatric: irritability, developmental delay, breath-holding spells

— Menstrual: cycle length, pad/tampon count, clots, duration; ask about fibroids, IUD type (copper increases loss, levonorgestrel decreases)

— GI: melena, hematochezia, dyspepsia, weight loss, change in stool caliber, family history of colorectal cancer or polyposis, prior H. pylori

— Dietary: red meat intake, vegan/vegetarian, infant formula vs cow's milk, tea/coffee with meals (inhibits absorption)

— Medications: PPIs, H2 blockers, antacids (reduce absorption), NSAIDs/ASA/anticoagulants (blood loss), bisphosphonates

— Surgical: bariatric procedures, gastrectomy, small bowel resection

— Obstetric: parity, interpregnancy interval <18 months, multiple gestation, postpartum hemorrhage

— Pulmonary/renal: hemoptysis (diffuse alveolar hemorrhage), hematuria, hemodialysis losses

— Travel/parasites: hookworm endemic areas, schistosomiasis

Key distinction: Pagophagia that resolves within days of starting iron is so characteristic it is virtually pathognomonic — patients will report the craving disappearing before lab values change. Use this as a treatment-response marker in follow-up phone visits before the 4-week CBC.

Symptom spectrum scales with rate of hemoglobin drop more than absolute value — chronic IDA tolerates Hb 6–7 g/dL while acute GI bleed at Hb 9 feels worse.

Classic complaints:

Targeted history (the Step 3 vignette will hide one of these):

Family history: celiac disease, hereditary hemorrhagic telangiectasia, von Willebrand disease, hemoglobinopathies (thalassemia mimic).

Physical Exam Findings and Hemodynamic Assessment

— Resting tachycardia, wide pulse pressure, systolic flow murmur (hyperdynamic state)

— Orthostatic vitals if acute bleeding suspected: drop in SBP ≥20 or HR rise ≥30 supine→standing suggests significant volume loss

— Hypotension at rest = decompensation → this is no longer outpatient management

— Glossitis (smooth, beefy tongue with atrophic papillae)

— Angular cheilitis (fissuring at oral commissures)

— Blue sclerae (collagen synthesis effect — uncommon but classic)

— Plummer-Vinson syndrome: IDA + dysphagia + esophageal web; ↑ risk of postcricoid squamous cell carcinoma

— Koilonychia (spoon nails) — late finding

— Telangiectasias on lips, tongue, fingertips → think hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) as bleeding source

— Diffuse non-scarring alopecia

Step 3 management: Hemodynamic triage drives disposition. Stable patient with chronic IDA → outpatient workup with same-week labs and endoscopy referral. Tachycardia + orthostasis + Hb <7 or active bleeding → ED for transfusion and inpatient endoscopy. A "stable" patient who is symptomatic at rest (chest pain, dyspnea, syncope) regardless of Hb number gets transfused — symptoms, not a threshold, drive the order.

General: pallor of conjunctivae, palmar creases, nail beds; pallor becomes visible around Hb <9 g/dL but is insensitive — do not rule out IDA on a "pink" exam.

Vital signs:

HEENT:

Skin/nails/hair:

Cardiopulmonary: tachypnea, S3 if high-output failure, flow murmur at LSB

Abdomen: epigastric tenderness (PUD), hepatosplenomegaly (alternative diagnosis: thalassemia, hematologic malignancy), masses

Rectal: digital rectal exam with stool guaiac is part of the initial IDA workup in any adult — document presence/absence of mass and stool color/blood

Pelvic (when menstrual loss suspected): bulky uterus → fibroids; cervical lesions

Diagnostic Workup — Initial Labs

— Microcytic anemia: MCV <80 fL, hypochromic (low MCH, MCHC)

— RDW elevated (>14.5%) — anisocytosis is an early IDA finding and helps separate from thalassemia

— Reticulocyte count low or inappropriately normal (inadequate response for degree of anemia)

— Thrombocytosis is common in IDA (reactive) — should normalize with treatment; persistent thrombocytosis after iron repletion → reconsider MPN or occult inflammation

— Ferritin <30 ng/mL is diagnostic of iron deficiency in otherwise healthy adults (sensitivity/specificity both excellent)

— Ferritin <15 highly specific; <45 reasonable cutoff in CKD/inflammatory states

— Serum iron low, TIBC high, transferrin saturation <20%

— In inflammation/ACD: ferritin can be falsely normal/high (acute phase reactant) — use TSAT <20% + soluble transferrin receptor or trial of iron

— CMP (renal function, LFTs)

— Reticulocyte index

— TSH (anemia workup)

— Pregnancy test in reproductive-age women

— Stool occult blood (FIT preferred over guaiac)

— Celiac serology (tissue transglutaminase IgA + total IgA) — recommended in all new IDA without obvious cause

— H. pylori testing (stool antigen or urea breath test) if dyspepsia or refractory IDA

— Urinalysis (hematuria)

Board pearl: Ferritin <30 + microcytic anemia = iron deficiency, full stop — no further confirmatory iron testing needed. The trap is the patient with CKD, RA, or obesity where ferritin is 80 but TSAT is 12% — that is functional iron deficiency and still warrants iron repletion (often IV).

CBC with differential and peripheral smear is the first test.

Iron studies — the diagnostic core:

Peripheral smear: microcytes, hypochromia, anisopoikilocytosis, pencil/cigar cells, target cells (fewer than thalassemia)

Additional initial labs based on suspicion:

Diagnostic Workup — Advanced and Source Identification

— All men with IDA

— All postmenopausal women with IDA

— Premenopausal women with IDA disproportionate to menstrual loss, GI symptoms, family history of CRC, age ≥40–50, or failure to respond to iron

— Bidirectional endoscopy (EGD + colonoscopy) is the standard; yield ~30–50% for clinically significant lesions

— If both negative and IDA persists: video capsule endoscopy for small bowel evaluation, then deep enteroscopy if lesion found

— Consider Meckel scan in young adults with obscure bleeding

— Pelvic exam, transvaginal ultrasound for fibroids/polyps

— Endometrial biopsy if age >45 or risk factors for endometrial cancer

— Von Willebrand workup if menorrhagia since menarche, family bleeding history, or postpartum hemorrhage

— Celiac serology positive → EGD with duodenal biopsies (villous atrophy)

— Consider autoimmune atrophic gastritis: anti-parietal cell and anti-intrinsic factor antibodies, gastrin, pepsinogen ratio

— H. pylori breath/stool test; eradicate and reassess

Key distinction: Mentzer index (MCV/RBC) — >13 favors IDA, <13 favors thalassemia trait. Useful screening when ferritin is borderline. But never use this alone; check ferritin and electrophoresis when the clinical picture is mixed.

Source workup is mandatory once IDA is confirmed — anemia is the symptom; bleeding or malabsorption is the diagnosis.

GI evaluation indications:

Gynecologic evaluation for heavy menstrual bleeding:

Malabsorption workup:

Urinary/pulmonary losses if unexplained: urinalysis, microscopy; chest imaging if hemoptysis (diffuse alveolar hemorrhage syndromes, idiopathic pulmonary hemosiderosis)

Hemoglobin electrophoresis if microcytosis persists despite repletion or if MCV is disproportionately low for degree of anemia (suspect concurrent thalassemia trait).

Risk Stratification and Management Logic

— Where to treat: outpatient (almost always) vs inpatient (active bleeding, hemodynamic instability, symptomatic severe anemia)

— Route of repletion: oral vs IV iron

— Whether to transfuse: separate decision from iron repletion

— Hb <7 g/dL in hemodynamically stable hospitalized patients

— Hb <8 g/dL in patients with cardiovascular disease, post-orthopedic/cardiac surgery

— Active bleeding + symptoms → transfuse regardless of number

— Transfusion does not treat iron deficiency — each unit gives only ~200 mg of iron, far less than typical deficit (1000–1500 mg)

— Mild-moderate anemia (Hb >9), tolerant GI tract, no malabsorption

— Pregnancy in first/early second trimester (often)

— Patient preference, cost concerns, no IV access issues

— Intolerance or failure of oral iron after 4–6 weeks

— Malabsorption: celiac, IBD, post-bariatric, atrophic gastritis

— Ongoing blood loss exceeding oral absorption (~25 mg/day max)

— CKD (especially on dialysis), heart failure with TSAT <20% and ferritin <300

— Need for rapid repletion: third-trimester pregnancy, preop within 6 weeks, severe symptomatic anemia not requiring transfusion

— Chemotherapy-associated anemia with functional iron deficiency

Step 3 management: The exam loves the question "patient on oral iron 6 weeks, no Hb response, ferritin still <20." Next step is NOT higher-dose oral iron — it is to verify adherence, then switch to IV iron and reconsider an occult bleeding source. Doubling oral dose worsens GI side effects without improving absorption (hepcidin block).

Once IDA is confirmed, three parallel decisions:

Transfusion thresholds (restrictive strategy per AABB):

Choosing oral vs IV iron — favor oral when:

Favor IV iron when:

Calculate total iron deficit (Ganzoni formula) or use fixed-dose protocols — most modern IV iron products allow 1000–1500 mg in 1–2 visits.

Pharmacotherapy — Oral Iron Regimens

— Ferrous sulfate 325 mg tablet = 65 mg elemental iron (cheapest, first line)

— Ferrous gluconate 324 mg = 38 mg elemental

— Ferrous fumarate 324 mg = 106 mg elemental

— Polysaccharide-iron complex, heme iron polypeptide, ferric maltol — better tolerated, more expensive

— 65–100 mg elemental iron every other day (or once daily on alternate days) is now preferred over TID dosing

— Rationale: oral iron transiently raises hepcidin for ~24 hours, blocking absorption of subsequent doses. Alternate-day dosing increases fractional absorption and reduces GI side effects

— Take on empty stomach when tolerated; with vitamin C 250 mg or orange juice to enhance absorption

— Avoid co-administration with calcium, dairy, antacids, PPIs, tea/coffee, levothyroxine, fluoroquinolones, tetracyclines (separate by 2–4 hours)

— Constipation, nausea, epigastric pain, metallic taste, dark/black stools (expected, not melena)

— Mitigation: alternate-day dosing, take with small food, lower elemental dose, switch preparation

— Continue 3–6 months after Hb normalizes to replete stores (ferritin target >100)

— Total course usually 4–6 months minimum

— Reticulocytosis in 7–10 days

— Hb rise ~1 g/dL per 2–3 weeks; recheck CBC at 4 weeks

— Hb increase <1 g/dL by 4 weeks = inadequate response

Board pearl: "Iron with orange juice, away from milk and calcium, every other morning on an empty stomach" is the most exam-correct counseling line. PPIs are a hugely underrecognized cause of oral iron failure — review the medication list before declaring treatment failure.

Preferred oral preparations (all equivalent in elemental iron delivery if dosed correctly):

Modern evidence-based dosing:

Side effects (30–70% of patients):

Duration:

Expected response:

Pharmacotherapy — IV Iron Formulations and Administration

— Iron sucrose (Venofer): 200–300 mg per infusion; multiple visits to reach total dose; very safe, often used in dialysis

— Ferric gluconate (Ferrlecit): 125 mg per dose; mostly historical/dialysis

— Ferumoxytol (Feraheme): 510 mg × 2 doses (1020 mg total); rapid

— Ferric carboxymaltose (Injectafer): 750 mg × 2 doses one week apart, or 15 mg/kg up to 1000 mg; risk of hypophosphatemia — check phosphate 2 weeks post-infusion

— Iron isomaltoside / ferric derisomaltose (Monoferric): 1000 mg single infusion; low hypersensitivity rate

— LMW iron dextran (INFeD): requires test dose; total dose infusion possible; higher anaphylaxis risk historically (mostly with old HMW dextran, now off market)

— Premedication with steroids/antihistamines not routinely recommended (may worsen infusion reactions); reserve for prior reactions or multiple drug allergies

— Monitor for hypersensitivity in first 30 minutes; modern formulations have anaphylaxis rates <1 in 200,000

— Fishbane reaction: transient flushing, chest/back tightness without hemodynamic compromise — pause infusion, do not give epinephrine; usually resolves and infusion can resume slower

Step 3 management: When the vignette gives a patient with IBD flare + IDA, oral iron is wrong — it worsens GI inflammation and is poorly absorbed. Choose IV iron. Same logic for post-bariatric, chronic GI blood loss exceeding absorption, and CKD stage 3–5.

IV iron is safe, effective, and increasingly first-line in malabsorption, intolerance, CKD, IBD, third-trimester pregnancy, and perioperative anemia.

Available formulations (US):

Administration:

Contraindications: known hypersensitivity, active bacteremia (relative — iron feeds organisms), first-trimester pregnancy (relative)

Monitoring post-IV iron: recheck CBC and ferritin at 4–8 weeks; do not recheck iron studies within 1–2 weeks (artifactually elevated).

Special Populations — Elderly and Renal/Hepatic Impairment

— IDA in this group has ~60% chance of an identifiable GI lesion; bidirectional endoscopy is non-negotiable absent contraindications

— Higher prevalence of atrophic gastritis, H. pylori, NSAID/anticoagulant use, malignancy, angiodysplasia

— Polypharmacy is the silent culprit — PPIs (now often used >5 years), levothyroxine, calcium supplements all impair oral iron

— Tolerance of oral iron is poor (constipation worsens functional decline); lower threshold for IV iron

— Cardiac comorbidity: anemia worsens HF and angina — transfusion threshold Hb <8 g/dL

— Functional assessment, fall risk, frailty drive aggressiveness of workup; goals-of-care conversation before colonoscopy in advanced dementia

— KDIGO: treat iron deficiency if TSAT ≤30% and ferritin ≤500 ng/mL in non-dialysis CKD, or TSAT ≤30% and ferritin ≤500 in dialysis patients with anemia/ESA use

— Functional iron deficiency from elevated hepcidin → IV iron preferred in CKD stage 3b–5 and all dialysis patients

— Hb target on ESA therapy: 10–11.5 g/dL; do not exceed 11.5 (CHOIR/TREAT — increased stroke/CV events)

— Iron sucrose and ferric gluconate have the longest dialysis safety record

— Ferritin elevated as acute-phase reactant in chronic liver disease; use TSAT and clinical context

— Avoid IV iron in active infection; cirrhotic patients with variceal bleeding need transfusion + endoscopic management first, iron repletion after stabilization

— Hemochromatosis must be excluded if ferritin >300 (men) / >200 (women) with TSAT >45% — do not give iron to these patients

Board pearl: In a hemodialysis patient with Hb 9, ferritin 200, TSAT 18%, on ESA — the answer is IV iron, not increasing the ESA dose. Iron deficiency is the most common cause of ESA hyporesponsiveness.

Elderly patients (>65):

CKD:

Hepatic impairment:

Special Populations — Pregnancy and Pediatrics

— Physiologic plasma volume expansion lowers Hb; anemia defined as Hb <11 g/dL T1/T3, <10.5 T2

— Iron requirement: ~1000 mg total over pregnancy; most prenatal vitamins provide only 27 mg elemental — often insufficient if deficient

— Screen with CBC at first prenatal visit and 24–28 weeks

— First line: oral iron 60–120 mg elemental daily (or alternate-day); ferrous sulfate standard

— IV iron indications in pregnancy:

· Intolerance or failure of oral iron

· Severe anemia (Hb <9) in second or third trimester

· <6 weeks until delivery and inadequate response

· Malabsorption

— Most US providers avoid IV iron in first trimester (safety data limited); ferric carboxymaltose and ferric derisomaltose are commonly used T2/T3

— Untreated IDA increases preterm birth, low birth weight, postpartum depression, transfusion at delivery

— Postpartum Hb <10 with symptoms → IV iron is often more effective than oral; transfusion only for symptomatic Hb <7 or hemodynamic compromise

— Highest risk: 9–24 months, especially with early cow's milk introduction (<12 mo), exclusive breastfeeding >6 mo without iron supplementation, prematurity

— Cow's milk: limit to <24 oz/day after age 1; causes occult GI blood loss + low iron content

— AAP universal screening with Hb at 12 months; risk-based after

— Treatment: 3–6 mg/kg/day elemental iron for 3 months after Hb normalizes

— IDA in infancy linked to long-term cognitive and behavioral deficits — repletion does not fully reverse → prevention matters

— Adolescent girls: screen at well visits if heavy menses, vegetarian, athlete

Key distinction: In pregnancy, a low ferritin (<30) is diagnostic even when Hb is still normal — treat to prevent late-pregnancy anemia. Do not wait for Hb to fall.

Pregnancy:

Postpartum:

Pediatrics:

Complications and Adverse Outcomes

— High-output heart failure in severe chronic anemia

— Worsening angina, MI in patients with CAD

— Cognitive impairment, particularly in elderly and children

— Restless legs syndrome, fatigue, depression

— Plummer-Vinson syndrome: dysphagia from postcricoid esophageal web, ↑ risk of squamous cell carcinoma of esophagus/hypopharynx

— Pica complications: lead poisoning (paint chips), dental erosion (ice), bowel obstruction (pagophagia is benign; geophagia can cause helminth infection)

— Pregnancy: preterm labor, LBW, increased peripartum transfusion, postpartum depression

— Pediatric: irreversible neurodevelopmental impact, breath-holding spells

— Missed underlying diagnosis: colorectal cancer, gastric cancer, celiac disease detected late

— GI: constipation, nausea, epigastric pain, diarrhea, black stools

— Tooth staining with liquid formulations (use straw, rinse mouth)

— Iron overdose in children — 60 mg/kg elemental is lethal; keep in childproof containers (#1 cause of pediatric poisoning death historically)

— Hypersensitivity reactions (rare with modern preparations, ~1:200,000 anaphylaxis)

— Hypophosphatemia — most common with ferric carboxymaltose; can cause osteomalacia/fractures with repeated dosing

— Extravasation → persistent brown skin staining

— Transient hypotension, headache, myalgia (Fishbane-like reactions)

— Theoretical infection risk — avoid during active bacteremia

CCS pearl: If a CCS case has the patient on ferric carboxymaltose × 2–3 cycles with new bone pain or fatigue not improving, order serum phosphate and 25-OH vitamin D. Recurrent dosing → hypophosphatemic osteomalacia. Switch to ferric derisomaltose or iron sucrose.

Complications of untreated IDA:

Complications of oral iron:

Complications of IV iron:

Complications of transfusion: TACO, TRALI, alloimmunization, iron overload (in repeated transfusion).

When to Escalate Care

— Active GI bleeding (melena, hematochezia, hematemesis) with hemodynamic instability

— Symptomatic anemia at rest: chest pain, dyspnea, syncope, altered mental status

— Hb <7 g/dL with symptoms, or <8 with cardiac disease

— Orthostatic hypotension, resting tachycardia >110, hypotension

— Suspected source requiring urgent intervention (massive variceal bleed, perforated ulcer)

— Gastroenterology: all IDA requiring endoscopy; obscure GI bleeding for capsule endoscopy/enteroscopy

— Hematology: refractory IDA despite IV iron, suspected concurrent hemoglobinopathy, hereditary iron-refractory IDA (TMPRSS6 mutations — IRIDA), unclear diagnosis

— Gynecology: menorrhagia not controlled with hormonal therapy, fibroids, suspected endometrial pathology

— Surgery: refractory upper/lower GI lesions, fibroid embolization referral, bariatric follow-up

— Nephrology: CKD with ESA management

— Maternal-fetal medicine: severe pregnancy anemia approaching delivery

— Identify IDA ≥4–6 weeks preop; treat with IV iron ± ESA to avoid intraop transfusion

— Major orthopedic, cardiac, oncologic surgery — IV iron reduces transfusion need by ~30%

Step 3 management: A patient scheduled for total hip replacement in 5 weeks with Hb 10.2 and ferritin 12 — do not start oral iron and wait. Order IV iron (e.g., 1000 mg ferric derisomaltose or 2 doses ferric carboxymaltose) to optimize Hb before surgery. This is a value-based care expectation.

Outpatient management is appropriate for the vast majority of IDA — stable hemodynamics, no active bleeding, capable of oral or scheduled IV iron.

ED referral / inpatient admission indications:

Specialty consultations:

Preoperative anemia clinic (increasingly standard):

Key Differentials — Other Microcytic Anemias

— Microcytosis disproportionate to anemia (MCV often 60s with Hb 11–12)

— Normal RDW (vs elevated in IDA), normal/elevated RBC count

— Ferritin normal or high; do not give iron — risk of overload

— Hb electrophoresis: ↑ HbA2 (β-thal trait); α-thal trait requires genetic testing (normal electrophoresis)

— Mentzer index <13

— Hepcidin-mediated iron sequestration

— Usually normocytic, but can be microcytic in chronic states

— Ferritin normal or elevated, low serum iron, low TIBC (key distinction from IDA where TIBC is high), TSAT low-normal

— Soluble transferrin receptor low in ACD, high in IDA

— Coexistence is common (IBD, RA, CKD, malignancy) — treat both

— Acquired (MDS, lead, alcohol, isoniazid, copper deficiency, zinc excess) or hereditary (X-linked, ALAS2)

— Ringed sideroblasts on bone marrow Prussian blue stain

— High serum iron, high ferritin, high TSAT (iron overload pattern)

— Pyridoxine trial for hereditary forms

— Microcytic anemia + basophilic stippling on smear

— Abdominal pain, neuropathy, cognitive effects; pediatric exposure to old paint

— Blood lead level; chelation if level high

Key distinction: TIBC direction is the cleanest separator: high TIBC = IDA, low TIBC = ACD, normal/high ferritin with high TSAT = thalassemia or sideroblastic. Master this single table and you will answer 80% of board questions on microcytic anemia.

Differential for microcytic anemia (MCV <80) — TAILS mnemonic: Thalassemia, Anemia of chronic disease (late), Iron deficiency, Lead poisoning, Sideroblastic anemia.

Thalassemia trait (α or β):

Anemia of chronic disease (anemia of inflammation):

Sideroblastic anemia:

Lead poisoning:

Copper deficiency: causes microcytic or macrocytic anemia + neutropenia; bariatric, excess zinc.

Key Differentials — Non-Microcytic Mimics and Coexisting Causes

— Often normocytic, normochromic; EPO deficiency primary

— Coexisting iron deficiency in 40–60% — always check iron studies before/with ESA

— Macrocytic by isolation, but mixed B12 + iron deficiency yields dimorphic smear with normal MCV — high RDW is the clue

— Always check B12 in post-bariatric, vegan, autoimmune atrophic gastritis (combines with iron loss)

— Reticulocytosis, ↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin

— IDA can develop in chronic intravascular hemolysis (PNH, prosthetic valves, march hemoglobinuria) from urinary hemosiderin loss — uniquely treated with iron

— Mild anemia (normocytic or macrocytic); always order TSH in anemia workup

— Elderly with cytopenias, dysplasia on smear; ferritin often elevated; refer hematology

— Pancytopenia, abnormal smear (teardrops, blasts, leukoerythroblastic picture)

— Normal MCV, ferritin normal, no treatment beyond prenatal vitamin

— Plasma volume expansion in endurance athletes; normal iron studies

— IRIDA (iron-refractory iron-deficiency anemia): TMPRSS6 mutations → high hepcidin → no response to oral iron; partial response to IV iron

— Hereditary hemorrhagic telangiectasia: recurrent epistaxis/GI bleeding; family history; mucocutaneous telangiectasias

— Von Willebrand disease: menorrhagia from menarche, mucocutaneous bleeding

Board pearl: A young woman with lifelong heavy menses, easy bruising, and IDA recurrent despite repletion should prompt vWF antigen, vWF activity (ristocetin cofactor), and factor VIII — von Willebrand disease is underdiagnosed and changes management (DDAVP, tranexamic acid, hormonal therapy choice).

Some patients present with fatigue and borderline normal MCV masking IDA, or with multifactorial anemia.

Anemia of CKD:

B12 / folate deficiency:

Hemolytic anemia:

Hypothyroidism:

MDS:

Bone marrow infiltration / aplastic anemia:

Pregnancy dilutional anemia:

Athletic / dilutional pseudoanemia:

Hereditary causes:

Secondary Prevention and Long-Term Plan

— H. pylori eradication if positive

— Celiac disease → gluten-free diet, expect ferritin normalization in 6–12 months

— Heavy menstrual bleeding → levonorgestrel IUD (first line for menorrhagia), combined oral contraceptive, tranexamic acid during menses, endometrial ablation, GnRH agonist, hysterectomy for refractory cases

— Discontinue/minimize NSAIDs; if anticoagulant is essential, optimize PPI cover and source control

— IBD: control inflammation to reduce bleeding and improve hepcidin

— Bariatric/atrophic gastritis → long-term scheduled iron monitoring; many require periodic IV iron

— Heme iron sources (red meat, poultry, fish) better absorbed than non-heme (legumes, leafy greens, fortified cereals)

— Vitamin C with non-heme iron meals

— Avoid tea, coffee, calcium-rich foods, dairy within 1–2 hours of iron-rich meals

— Vegan/vegetarian: consider routine supplementation, especially women

— Continue oral iron 3–6 months after Hb normalizes; target ferritin >50–100

— Document a "complete" iron course in chart before declaring repletion

— Pregnant patients: CBC postpartum 4–6 weeks

— Menorrhagia: CBC + ferritin q6–12 months

— Post-bariatric: CBC, ferritin, B12, folate, vitamin D yearly

— Hemodialysis: monthly Hb, TSAT/ferritin quarterly

— Recurrent IDA without identified source: repeat endoscopy or capsule study

— Colorectal cancer screening up to date — important when bidirectional endoscopy was done for IDA workup, document next screening interval

Step 3 management: When the source is heavy menstrual bleeding in a woman not desiring pregnancy, levonorgestrel-releasing IUD is the single most effective intervention — reduces blood loss by ~90% and often achieves amenorrhea. This is a more durable answer than oral iron alone.

Treat the cause, not just the lab:

Dietary counseling:

Iron stores replacement:

Ongoing monitoring schedule for high-risk patients:

Vaccinations and preventive care:

Follow-Up, Monitoring, and Counseling

— Phone or visit at 2 weeks: tolerance check, adherence, symptom response (pica resolution, energy)

— CBC at 4 weeks: expect Hb rise ≥1 g/dL; reticulocytosis at 1–2 weeks

— CBC + ferritin at 8–12 weeks: confirm normalization trajectory

— CBC + ferritin at end of treatment course (~6 months) to document repletion

— Then surveillance based on underlying cause

— Confirm adherence (most common cause)

— Review interfering medications and timing (PPI, calcium, levothyroxine, antacids, tea/coffee)

— Reconsider ongoing blood loss (occult GI, menstrual)

— Check for inflammation / ACD component

— Verify diagnosis: is this thalassemia trait or sideroblastic?

— Switch to IV iron

— Consider IRIDA, refer hematology

— Expected dark stools — not melena

— Constipation prevention: hydration, fiber, stool softener if needed

— Take iron in morning on empty stomach, with vitamin C

— Avoid concurrent dairy/calcium, coffee, tea, antacids

— Continue iron 3–6 months after Hb normalizes

— Store away from children (poison risk)

— Gradual return to exercise as Hb improves

— Reassure on cognitive symptoms — improve over weeks

— Iron studies and CBC are inexpensive — use them generously

— IV iron costs ($500–$3000 per course) often less than transfusion + length of stay; payer pre-authorization may be needed

CCS pearl: Schedule the follow-up CBC at 4 weeks and the iron studies at 8–12 weeks (not the same day). Order both on the CCS interface at the time of starting iron — anticipatory ordering scores points and reflects ambulatory continuity.

Standard follow-up cadence after starting iron:

Inadequate response evaluation (Hb rise <1 g/dL at 4 weeks):

Counseling points (document in chart):

Rehabilitation/lifestyle:

Health system context:

Ethical, Legal, and Patient Safety Considerations

— Disclose hypersensitivity risk (rare anaphylaxis), hypophosphatemia with ferric carboxymaltose, persistent skin staining from extravasation

— Document discussion; many institutions require written consent for first IV iron infusion

— Patients may refuse RBC transfusion but often accept IV iron, ESAs, and tranexamic acid as bloodless alternatives

— Document specific products patient accepts/refuses; involve patient advocate; respect autonomy in competent adults

— In pediatric patients of JW parents with life-threatening anemia, court order may be sought emergently — know your institutional pathway

— Severe iron deficiency in an infant from prolonged unmodified cow's milk feeding or food insecurity may trigger child protective services consideration when neglect is suspected

— Lead poisoning is reportable to public health in most states

— Hospitalized patient discharged after GI bleed with new IDA — must have outpatient GI follow-up arranged, iron prescription filled at discharge (medication reconciliation), repeat CBC scheduled within 1–2 weeks

— Pregnant patient identified with IDA late in pregnancy — confirm L&D team aware; postpartum Hb plan documented

— Failure to document colonoscopy recommendation in elderly patient with IDA is a recognized malpractice pattern when missed CRC presents later

— Pediatric iron overdose remains a leading cause of poisoning fatality — counsel on childproof storage at every prescription

— Drug interactions: levothyroxine absorption reduced — separate by 4 hours and recheck TSH after starting iron

— Religious dietary practices (vegetarian Hinduism, Lent fasting) affect dietary iron — incorporate into counseling without judgment.

Board pearl: In a Jehovah's Witness with Hb 6.5 and IDA, the correct combination is high-dose IV iron + erythropoiesis-stimulating agent ± tranexamic acid for source bleeding — never just "decline transfusion and discharge." Document the bloodless management plan and consult hematology.

Informed consent for IV iron:

Transfusion refusal — Jehovah's Witnesses:

Mandatory reporting and abuse considerations:

Transition-of-care risks (high-yield Step 3):

Patient safety in oral iron:

Cultural and dietary considerations:

High-Yield Associations and Rapid-Fire Facts

Key distinction: Ferritin <30 → IDA. Ferritin <100 with TSAT <20% in HF/CKD → functional iron deficiency → IV iron indicated. These are two different exam triggers — know both numerical cutoffs cold.

Plummer-Vinson = IDA + esophageal web + dysphagia → ↑ squamous cell carcinoma risk.

Pagophagia (ice craving) is the most specific pica for iron deficiency — resolves before lab values normalize.

Mentzer index = MCV / RBC count; >13 IDA, <13 thalassemia trait.

Ferritin <30 = iron deficiency in healthy adults; <45–100 with TSAT <20% in inflammation = functional iron deficiency.

TIBC: ↑ in IDA, ↓ in ACD — single best lab discriminator.

Thrombocytosis with IDA is reactive; resolves with iron repletion. Persistent thrombocytosis → reconsider myeloproliferative neoplasm.

Reticulocytosis at 7–10 days after starting iron = treatment working.

Restless legs syndrome — check ferritin; replete to ferritin >75–100 even if anemia is mild.

Oral iron is best absorbed on alternate days due to hepcidin physiology.

PPIs and antacids are major underrecognized causes of oral iron failure.

Bariatric surgery (especially Roux-en-Y): plan for lifelong iron monitoring; many patients need scheduled IV iron.

Hemodialysis patients: IV iron + ESA; oral iron is largely ineffective.

Ferric carboxymaltose → hypophosphatemia (check 2 weeks post).

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu): recurrent epistaxis + telangiectasias + IDA + AVMs.

Iron-refractory IDA (IRIDA): TMPRSS6 mutation → persistently high hepcidin; only partial response to IV iron.

Cow's milk before 12 months is the classic pediatric cause of IDA.

Post-gastrectomy/atrophic gastritis: low acid → reduced ferric to ferrous conversion → impaired absorption.

Celiac serology (tTG-IgA + total IgA) is part of every unexplained IDA workup.

AABB transfusion threshold: Hb <7 stable, <8 with cardiac disease.

Treatment of IDA in HF (FAIR-HF, AFFIRM-AHF): IV iron improves symptoms and reduces hospitalizations in HFrEF with iron deficiency, even without anemia (TSAT <20% or ferritin <100, or ferritin 100–300 with TSAT <20%).

Board Question Stem Patterns

Stem: 62-year-old man, fatigue, Hb 9.5, MCV 72, ferritin 8. Next step?

Answer: EGD + colonoscopy (not "start oral iron," not "fecal occult blood testing as next step"). Source must be found in any man or postmenopausal woman.

Stem: 35-year-old woman with menorrhagia, on ferrous sulfate 325 mg TID for 8 weeks, Hb 9 → 9.5, reports nausea and stops doses. Next step?

Answer: IV iron (and address menorrhagia with levonorgestrel IUD or hormonal therapy). Not "switch to ferrous gluconate," not "double the dose."

Stem: Mediterranean ancestry, MCV 65, Hb 11.5, RDW normal, ferritin 80. Next step?

Answer: Hemoglobin electrophoresis. Do not give iron.

Stem: Dialysis patient on epoetin, Hb 9, ferritin 250, TSAT 16%. Next step?

Answer: IV iron, not increase ESA dose.

Stem: 32 weeks pregnant, Hb 8.5, ferritin 6, oral iron intolerant. Next step?

Answer: IV iron (ferric carboxymaltose or ferric derisomaltose).

Stem: Hb 10 with low ferritin, elective hip arthroplasty in 5 weeks. Best management?

Answer: IV iron preoperatively — not transfusion, not delay surgery indefinitely.

Stem: Young woman with chronic diarrhea, IDA refractory to oral iron, bloating. Next step?

Answer: Tissue transglutaminase IgA + total IgA, then EGD with duodenal biopsy.

Stem: 14-month-old, pale, drinks 32 oz whole milk daily, Hb 8, MCV 65. Best initial step?

Answer: Limit cow's milk to <24 oz/day + start oral iron 3–6 mg/kg/day elemental; check lead level.

Answer features IV iron + ESA + tranexamic acid, not transfusion.

Step 3 management: Whenever the question gives ferritin <30 and asks for the next test, the answer is almost never another iron study — it is the source workup (endoscopy, celiac serology, gynecologic evaluation) or treatment initiation.

Pattern 1 — The classic GI source trap:

Pattern 2 — The treatment-failure switch:

Pattern 3 — The thalassemia mimic:

Pattern 4 — The CKD ESA hyporesponse:

Pattern 5 — The pregnancy late-trimester anemia:

Pattern 6 — The preop optimization:

Pattern 7 — The celiac giveaway:

Pattern 8 — The pediatric milk anemia:

Pattern 9 — The Jehovah's Witness bloodless management:

One-Line Recap

Iron deficiency anemia is diagnosed by ferritin <30 with microcytic anemia, demands a source workup (bidirectional endoscopy in men and postmenopausal women, gynecologic and celiac evaluation in younger women), and is treated with alternate-day oral iron first-line — escalating to IV iron for intolerance, malabsorption, CKD, IBD, late-trimester pregnancy, or preoperative optimization — with continued repletion 3–6 months beyond Hb normalization and ongoing surveillance directed at the underlying cause.

Board pearl: The single most tested IDA error on Step 3 is starting iron in an older adult without scheduling bidirectional endoscopy. The second is giving more oral iron to a non-responder instead of switching to IV iron and reassessing the source. Master those two moves and the topic is yours.

Diagnose: CBC + iron studies; ferritin <30 = IDA; high TIBC and RDW, low TSAT confirm. Always check celiac serology and consider H. pylori in unexplained cases.

Find the source: Bidirectional endoscopy is mandatory in men and postmenopausal women; gynecologic evaluation in menstruating women; capsule endoscopy if both negative and IDA persists.

Treat smart: Oral ferrous sulfate 65–100 mg elemental every other day on empty stomach with vitamin C; switch to IV iron (ferric carboxymaltose, ferric derisomaltose, iron sucrose) for intolerance, malabsorption, CKD/HF functional deficiency, late pregnancy, or preop optimization; continue 3–6 months post Hb normalization.

Prevent recurrence: Treat the cause (levonorgestrel IUD for menorrhagia, gluten-free diet for celiac, H. pylori eradication, NSAID discontinuation, lifelong monitoring after bariatric surgery), document follow-up CBC at 4 weeks and ferritin at 8–12 weeks, and never forget that anemia is the symptom — the bleeding lesion or malabsorption is the diagnosis.