Pregnancy, Childbirth & Puerperium

Anemia in pregnancy: workup and management

Clinical Overview and When to Suspect Anemia in Pregnancy

— 1st trimester: Hb <11.0 g/dL (Hct <33%)

— 2nd trimester: Hb <10.5 g/dL (Hct <32%)

— 3rd trimester: Hb <11.0 g/dL (Hct <33%)

— Postpartum: Hb <10.0 g/dL

— Fatigue, exertional dyspnea, pica (ice = pagophagia is classic for IDA), restless legs

— Pallor of conjunctivae/nail beds, glossitis, koilonychia

— Multiparity, short interpregnancy interval (<18 months), adolescent pregnancy, twin gestation, vegetarian/vegan diet

— Heavy menses prior to conception, GI disease (IBD, celiac, prior bariatric surgery)

— African, Mediterranean, or Southeast Asian ancestry (hemoglobinopathy/thalassemia risk)

Board pearl: A pregnant patient with Hb 10.2 g/dL at 26 weeks who craves ice cubes has iron deficiency anemia until proven otherwise — order ferritin first, do not stop at MCV.

Definition (CDC/ACOG trimester-specific cutoffs):

Physiologic vs pathologic: Plasma volume expands ~50% while RBC mass expands only ~25%, producing dilutional anemia that nadirs around 28–32 weeks. A modest Hb drop is expected; values below the cutoffs are pathologic.

Epidemiology: Anemia affects ~25% of pregnancies in the US; iron deficiency (IDA) is by far the most common cause (>75%), followed by folate deficiency, thalassemia trait, anemia of chronic disease, and hemoglobinopathies (sickle cell).

When to suspect beyond routine screening:

Universal screening: CBC at the initial prenatal visit and again at 24–28 weeks (paired with the glucose tolerance test). Repeat any time symptoms or risk factors arise.

Why it matters: Maternal anemia raises risk of preterm birth, low birth weight, postpartum hemorrhage decompensation, transfusion, postpartum depression, and impaired neurodevelopment in the infant.

Presentation Patterns and Key History

— Disproportionate fatigue, lightheadedness, palpitations, exertional dyspnea, headache

— Pica (ice, clay, starch) — highly specific for iron deficiency

— Restless legs syndrome — strongly linked to low ferritin (<75 ng/mL)

— Hair shedding, brittle nails, cheilosis, sore tongue

— Cold intolerance, poor concentration ("brain fog")

— Vegetarian/vegan, low red meat, excess milk/tea (inhibits iron absorption)

— Celiac, IBD, H. pylori, prior Roux-en-Y bypass or sleeve gastrectomy → impaired iron, B12, folate absorption

— Chronic NSAID/PPI use → blunted iron uptake

— Heavy menstrual bleeding before conception (depleted stores entering pregnancy)

— Short interpregnancy interval, grand multiparity

— Twin/triplet gestation (doubled iron demand)

— Prior postpartum hemorrhage

— Mediterranean, Middle Eastern, African, Southeast Asian → thalassemia, sickle cell, G6PD

— Family history of splenectomy, gallstones in youth, transfusion dependence → hereditary hemolytic anemia

— Sulfa drugs, nitrofurantoin (G6PD-mediated hemolysis)

— Methyldopa, penicillins (immune hemolysis)

— Antiepileptics (phenytoin, valproate) → folate depletion

— Metformin, prolonged PPI → B12 deficiency

— Melena, hematochezia, hematemesis, hematuria

— Jaundice, dark urine (hemolysis)

— Severe pallor with tachycardia >110 or SBP <100 → acute blood loss

Key distinction: Physiologic anemia of pregnancy is normocytic and asymptomatic; if the patient has symptoms or an abnormal MCV, it is pathologic. Always ask about pica and restless legs — they are nearly pathognomonic clues.

Symptom profile — often subtle in pregnancy because fatigue and dyspnea overlap with normal gestation:

Dietary and GI history:

Reproductive history:

Family/ancestry history:

Medication and exposure history:

Red flag symptoms demanding urgent workup:

Physical Exam Findings and Hemodynamic Assessment

— Pallor of conjunctivae, palmar creases, nail beds, oral mucosa

— Jaundice/scleral icterus → hemolysis or B12/folate deficiency (ineffective erythropoiesis)

— Glossitis, angular cheilitis, atrophic tongue — iron, B12, or folate deficiency

— Koilonychia (spoon nails) — chronic severe IDA

— Resting tachycardia (HR >100) common with Hb <9

— Wide pulse pressure, bounding pulses, systolic flow murmur at left sternal border (hyperdynamic state — often physiologic but accentuated)

— Orthostatic changes suggest volume loss in addition to anemia

— S3 gallop in severe anemia (high-output state)

— Pulmonary crackles raise concern for high-output failure or coexistent peripartum cardiomyopathy

— Splenomegaly → thalassemia, hemolytic anemia, hemoglobinopathy

— Hepatomegaly → chronic hemolysis, infiltrative disease

— Decreased vibratory and proprioceptive sense, ataxia, positive Romberg

— Hyperreflexia, paresthesias — subacute combined degeneration

— Cognitive slowing, depression

— Petechiae, ecchymoses → consider concurrent thrombocytopenia (HELLP, TTP, ITP)

— Leg ulcers in sickle cell disease

— Fundal height for IUGR (chronic anemia → placental insufficiency)

— Fetal heart tones; consider NST/BPP if Hb <8 or symptomatic

— Estimated blood loss tracking if peripartum

Step 3 management: Any pregnant patient with Hb <7, hemodynamic instability, ongoing bleeding, or signs of fetal compromise needs inpatient admission, type & screen, IV access ×2, and OB consultation. Outpatient oral iron is appropriate only for stable, mildly–moderately anemic patients without active bleeding.

General appearance:

Vital signs:

Cardiopulmonary:

Abdominal:

Neurologic (B12 specific):

Skin and mucosa:

Obstetric assessment:

Diagnostic Workup — Initial Labs

— CBC with RBC indices (MCV, MCH, MCHC, RDW)

— Peripheral smear

— Reticulocyte count (or reticulocyte production index)

— Ferritin — single best test for iron deficiency in pregnancy

— Serum iron, TIBC, transferrin saturation

— CMP (renal/hepatic function affects EPO, drug dosing)

— Microcytic (MCV <80): IDA, thalassemia, anemia of chronic disease (late), lead, sideroblastic

— Normocytic (MCV 80–100): acute blood loss, early IDA, ACD, hemolysis, dilutional, renal

— Macrocytic (MCV >100): folate, B12, hypothyroidism, liver disease, drugs (HU, MTX, AZT)

— <30 ng/mL = iron deficiency (sensitivity ~90%, specificity ~99%) — diagnostic, do not need further iron studies

— 30–100 ng/mL with elevated CRP → may still be deficient (ferritin is acute-phase)

— Transferrin saturation <16% supports IDA when ferritin equivocal

— High RDW + low MCV → IDA (anisocytosis from mixed populations)

— Normal RDW + low MCV + normal-to-high RBC count → thalassemia trait (Mentzer index MCV/RBC <13)

— Hypochromic microcytic + pencil cells → IDA

— Target cells, basophilic stippling → thalassemia, lead

— Hypersegmented neutrophils, oval macrocytes → B12/folate

— Schistocytes → MAHA (HELLP, TTP, DIC) — obstetric emergency

— Sickle cells, Howell-Jolly bodies → sickle cell disease

Board pearl: In a pregnant patient with microcytic anemia, ferritin <30 confirms IDA — start oral iron without ordering hemoglobin electrophoresis first. Reserve electrophoresis for non-responders or those with normal ferritin.

First-line panel (order simultaneously to avoid sequential delays):

MCV-based framework:

Ferritin interpretation in pregnancy:

RDW clue:

Peripheral smear pearls:

Always check prenatal records for baseline Hb at intake (compare with 24–28 week screen).

Diagnostic Workup — Advanced/Confirmatory Studies

— Normal/high ferritin + microcytosis → hemoglobin electrophoresis with HPLC

— Universal hemoglobinopathy screening is recommended at first prenatal visit for at-risk ancestry (ACOG); offer partner testing if positive.

— Serum B12 (<200 pg/mL deficient; 200–400 borderline → check methylmalonic acid and homocysteine)

— RBC folate or serum folate (less reliable, affected by recent intake)

— TSH, LFTs

— Reticulocyte count — low in nutritional, high in hemolysis/recovery

— LDH (elevated), haptoglobin (low), indirect bilirubin (elevated)

— Direct antiglobulin test (Coombs) — positive in autoimmune hemolysis

— G6PD level (defer testing during acute hemolysis — false normal)

— Peripheral smear for schistocytes vs spherocytes vs sickle cells

— Differentiate HELLP, preeclampsia with severe features, AFLP, TTP, HUS with: BP, urine protein, AST/ALT, platelets, PT/PTT/fibrinogen, ADAMTS13 if TTP suspected

— Fibrinogen <200 in pregnancy is abnormal — consider DIC/abruption

— Stool occult blood if IDA out of proportion to gestation, age >35, or refractory

— Endoscopy/colonoscopy generally deferred until postpartum unless life-threatening bleeding

— Celiac serology (tissue transglutaminase IgA) if refractory IDA

Key distinction: B12 deficiency in pregnancy mimics folate on CBC, but only B12 causes neurologic deficits — and giving folate alone in B12 deficiency worsens neurologic disease. Always check B12 before treating empirically with folate alone.

When iron studies don't fit:

HbA2 >3.5% → β-thalassemia trait

Normal electrophoresis with microcytosis → suspect α-thalassemia (need genetic testing: α-globin gene deletion analysis)

HbS, HbC, HbE bands → hemoglobinopathy

Macrocytic workup:

Hemolysis workup (if jaundice, elevated retic, or schistocytes):

MAHA/obstetric-specific:

GI evaluation:

Bone marrow biopsy: rarely needed; reserve for unexplained pancytopenia or suspected hematologic malignancy.

Risk Stratification and First-Line Management Logic

— Mild (Hb 10–10.9): outpatient oral iron, dietary counseling, recheck in 4 weeks

— Moderate (Hb 7–9.9): oral iron trial first; if no response in 2–4 weeks or 3rd trimester → IV iron

— Severe (Hb <7): IV iron preferred; consider transfusion if symptomatic, near delivery, or active bleeding

— Critical (Hb <6 or symptomatic): transfuse PRBCs

— Early pregnancy → time for oral iron to work (8–10 weeks to correct)

— >34 weeks with moderate-severe anemia → IV iron (oral too slow; need adequate Hb for delivery)

— Goal: Hb ≥11 entering labor to tolerate average 500 mL (vaginal) or 1000 mL (cesarean) blood loss

— Hb <9 in 2nd/3rd trimester

— Intolerance or non-response to oral iron after 2–4 weeks

— Malabsorption (IBD, celiac, post-bariatric)

— Need rapid correction (<8 weeks to delivery, planned cesarean)

— Severe symptoms or restless legs not responding to oral

— IDA → iron repletion + dietary counsel

— B12 → IM cyanocobalamin 1000 mcg, then maintenance

— Folate → 1–5 mg daily oral (most prenatal vitamins have 0.4–1 mg)

— Thalassemia trait → no iron unless coexistent IDA proven by ferritin; genetic counseling

— Hemolysis → treat underlying cause; folate supplementation 1 mg daily

Step 3 management: A patient at 35 weeks with Hb 8.2 and ferritin 9 has failed 6 weeks of oral iron — switch to IV iron (ferric carboxymaltose or iron sucrose), not continued oral, to ensure adequate Hb before delivery.

Stratify by severity and gestational age:

Gestational age modifies urgency:

Choose oral vs IV iron — favor IV when:

Treat the cause, not just the number:

Multidisciplinary triggers: MFM consult for Hb <8, hemoglobinopathy, hemolytic anemia, transfusion-dependent disease, or planned IV iron in patients with prior reactions.

Pharmacotherapy — First-Line Iron Regimens

— Ferrous sulfate 325 mg (65 mg elemental iron) — cheapest, most studied

— Alternatives: ferrous gluconate (36 mg elemental), ferrous fumarate (106 mg elemental)

— Dose: 40–100 mg elemental iron — current evidence supports alternate-day dosing (improves absorption by reducing hepcidin spike) and equal Hb response with fewer side effects

— Take on empty stomach with vitamin C (orange juice); avoid milk, calcium, tea, coffee, PPIs within 2 hours

— Expected reticulocytosis in 7–10 days; Hb rise of ~1 g/dL per 2–3 weeks

— Continue 3 months after Hb normalizes to replenish stores

— Nausea, constipation, dark stools, metallic taste, epigastric pain

— Manage: lower dose, take with small snack, add stool softener, alternate-day dosing, switch formulation

— Iron sucrose (Venofer): 200 mg per infusion, multiple sessions; well-studied in pregnancy

— Ferric carboxymaltose (Injectafer): 750 mg × 2 doses one week apart — efficient, but risk of hypophosphatemia

— Ferric derisomaltose (Monoferric): up to 1000 mg single dose

— Low-molecular-weight iron dextran: total dose infusion possible; test dose required

— Avoid IV iron in 1st trimester generally — limited safety data; use after 13 weeks

— Vital signs; watch for Fishbane reaction (transient flushing, myalgia) — pause, do not give steroids/antihistamines reflexively

— True anaphylaxis is rare with newer formulations

— Folate: 1 mg PO daily (5 mg if hemoglobinopathy, multiple gestation, MTHFR)

— B12: 1000 mcg IM weekly × 4, then monthly; oral 1000–2000 mcg daily if dietary cause

Board pearl: Alternate-day oral iron dosing (e.g., 65 mg every other day) produces equivalent Hb improvement with fewer GI side effects than daily dosing — high-yield 2024 update.

Oral iron — first line for mild-moderate IDA in early pregnancy:

Oral iron side effects (40–70% of patients):

IV iron formulations — pregnancy-relevant:

Monitoring during IV iron:

Other deficiencies:

Transfusion, IV Iron Practicalities, and Peripartum Pharmacology

— Hb <6 g/dL (almost always transfuse)

— Hb 6–7 with symptoms, cardiac disease, or anticipated delivery

— Active hemorrhage with hemodynamic instability

— Sickle cell crisis with severe anemia or stroke risk (consider exchange transfusion)

— Goal post-transfusion Hb: 7–8 (non-bleeding); >8 if cardiac/symptomatic; ≥10 peripartum if ongoing bleed

— Type & screen at admission for any labor patient with Hb <10

— Leukoreduced, CMV-safe, Rh-matched products

— Anti-D prophylaxis if Rh-negative receives Rh-positive blood (emergency situations)

— 1 unit PRBC raises Hb ~1 g/dL

— Infusion center or outpatient OB infusion suite

— Premedication generally not required; counsel on Fishbane reaction

— Recheck CBC and ferritin 4 weeks post-infusion

— Check phosphate at 2 weeks after ferric carboxymaltose if repeat dosing planned

— Reserved for CKD-associated anemia, Jehovah's Witnesses refusing transfusion, or selected refractory cases

— Epoetin alfa or darbepoetin; iron repletion must be adequate first

— Target Hb 10–11, not higher (thrombotic risk)

— Tranexamic acid 1 g IV within 3 hours of PPH (WOMAN trial)

— Active management of third stage: oxytocin 10 U IM/IV after delivery

— Cell salvage acceptable in obstetrics (cesarean with anticipated large loss)

— Strongly consider for Hb <9 postpartum, especially with PPH; faster recovery than oral iron, improves fatigue and breastfeeding success.

CCS pearl: For a laboring patient with Hb 6.5, the CCS sequence is: two large-bore IVs, type & cross 2 units PRBC, transfuse, continuous fetal monitoring, anesthesia and OB consult, location: Labor & Delivery → consider OR if bleeding.

PRBC transfusion indications in pregnancy:

Transfusion practicalities:

IV iron — administration logistics:

Erythropoiesis-stimulating agents (ESAs):

Adjuncts in peripartum hemorrhage with anemia:

Postpartum IV iron:

Special Populations — Renal, Hepatic, and Older Gravidas

— Anemia is multifactorial: EPO deficiency, iron deficiency, blood loss from dialysis, uremic platelet dysfunction

— Check iron studies, EPO levels, PTH, vitamin D

— Target Hb 10–11 with ESAs + IV iron (oral often inadequate)

— Coordinate with nephrology; intensified dialysis (≥36 hours/week) improves maternal and fetal outcomes

— Pre-eclampsia risk markedly elevated; preconception counseling essential

— Cirrhosis or AFLP → coagulopathy compounds bleeding risk

— Acute fatty liver of pregnancy: anemia + thrombocytopenia + transaminitis + hypoglycemia + coagulopathy → deliver promptly

— Avoid iron overload in chronic liver disease; monitor ferritin trends

— Higher baseline rates of fibroids, heavy menses pre-pregnancy → entering pregnancy iron-depleted

— Higher rates of GI pathology — lower threshold for celiac serology, FOBT, and postpartum endoscopy if anemia disproportionate

— Consider screening for occult malignancy if anemia refractory or weight loss present

— Roux-en-Y, sleeve gastrectomy → impaired iron, B12, folate, thiamine, vitamin D absorption

— Baseline and trimester-by-trimester labs for all micronutrients

— Often need IV iron and parenteral B12; oral rarely sufficient

— Pregnancy ideally delayed 12–24 months post-bariatric surgery

— Higher anemia rates due to ongoing growth and competing iron demands

— Diet often deficient; aggressive supplementation and nutrition counseling

— Iron sucrose: no renal adjustment needed

— Ferric carboxymaltose: caution with hypophosphatemia in CKD

— ESAs: titrate slowly; avoid Hb >11.5 (thrombotic risk)

Key distinction: In CKD-related anemia of pregnancy, iron alone won't correct it — you need ESAs because EPO production is impaired. In contrast, dilutional anemia in healthy pregnancy needs no treatment if Hb above trimester cutoff.

CKD in pregnancy:

Hepatic disease:

Advanced maternal age (≥35):

Obesity and post-bariatric pregnancy:

Adolescent pregnancy:

Drug dosing adjustments:

Special Populations — Hemoglobinopathies, Multiples, and Postpartum

— Continue folic acid 4–5 mg daily (high-dose); avoid iron unless ferritin proven low

— Increased risk: VTE, preeclampsia, IUGR, preterm birth, pain crises, ACS

— Prophylactic transfusion not routine; reserve for stroke history, severe anemia, recurrent ACS, or before cesarean

— Hydroxyurea discontinued preconception (teratogenic); continue ACE inhibitors only if benefit outweighs (usually stop)

— Pneumococcal, meningococcal, influenza vaccines current

— Multidisciplinary care: hematology + MFM

— Trait carriers usually require only folate; iron supplementation only if proven IDA by ferritin (avoid iron overload)

— β-thalassemia major: chelation paused or modified (deferoxamine considered safer than deferasirox); transfusion-dependent; cardiac surveillance

— Partner screening and genetic counseling essential — risk of hydrops fetalis (α-thal major) or transfusion-dependent offspring

— Iron demand nearly doubled; routine prenatal vitamin insufficient

— Start prophylactic iron 60–100 mg elemental + folate 1 mg by 2nd trimester

— Screen for anemia each trimester; lower threshold for IV iron

— Document specific blood-product preferences (some accept albumin, factor concentrates, cell salvage)

— Aggressive preoperative optimization — IV iron, ESAs, target Hb >12 before delivery

— Consider tranexamic acid, cell salvage, hemostatic surgery techniques

— Affects ~20–30% of mothers; linked to fatigue, depression, impaired bonding/lactation

— Oral iron 3 months if mild

— IV iron if moderate-severe — superior recovery; safe during lactation

— Transfuse if Hb <7 with symptoms

Step 3 management: A G2P1 with sickle cell disease at 12 weeks needs folate 4 mg daily, stop hydroxyurea (if not already), hematology + MFM co-management, baseline labs (CBC, retic, LDH, ferritin, type & screen with extended phenotype), and vaccines updated.

Sickle cell disease:

Thalassemia:

Twin/multiple gestation:

Jehovah's Witness patients:

Postpartum anemia (Hb <10 within 48 hours of delivery):

Complications and Adverse Outcomes

— Increased peripartum mortality when Hb <7

— Decreased reserve for hemorrhage; PPH morbidity amplified

— Higher transfusion rates; transfusion reactions and alloimmunization

— Postpartum depression (1.5–3× risk with anemia)

— Impaired lactation, prolonged fatigue, delayed return to baseline function

— Cardiac decompensation in pre-existing heart disease (high-output failure)

— Infection susceptibility — endometritis, wound infection

— Preterm birth (RR ~1.6 with moderate IDA)

— Low birth weight / SGA from placental insufficiency

— Neonatal iron stores compromised when maternal Hb <9 in 3rd trimester

— Impaired neurodevelopment, lower cognitive and motor scores at 1–2 years

— Increased perinatal mortality at Hb <6

— B12 deficiency: irreversible neurologic damage if untreated; neonatal B12 deficiency from breastfeeding mother → developmental regression

— Folate deficiency: neural tube defects (if periconceptional), placental abruption, possible preterm labor

— Sickle cell: acute chest syndrome, stroke, VTE, fetal demise, IUGR

— Thalassemia major: cardiac iron overload exacerbated by pregnancy, heart failure

— Hemolytic anemia: hyperbilirubinemia in neonate, hydrops in alloimmune cases

— IV iron: anaphylactoid reactions (rare with modern products), hypophosphatemia

— Transfusion: TRALI, TACO (especially in pregnancy with high cardiac output), alloimmunization affecting future pregnancies

— Over-supplementation: iron overload in thalassemia trait given empiric iron without ferritin check

Board pearl: Anti-D alloimmunization from a transfusion in pregnancy can complicate future gestations with hemolytic disease of the newborn — always use Rh-matched blood and document antibody screen postpartum.

Maternal complications:

Fetal/neonatal complications:

Specific etiology complications:

Iatrogenic:

When to Escalate Care — Inpatient Triage and Consults

— Hb <7 with symptoms (tachycardia, dyspnea, chest pain, syncope)

— Active bleeding (GI, vaginal, postpartum)

— Hemolytic crisis with hemodynamic instability, jaundice progression, or organ dysfunction

— Schistocytes + thrombocytopenia → rule out HELLP, TTP, AFLP, HUS — obstetric emergency

— Sickle cell vaso-occlusive crisis, ACS, or stroke symptoms

— Severe B12 deficiency with neurologic symptoms

— Massive transfusion protocol activation (>4 units in 1 hour or anticipated >10 units)

— Hemodynamic instability despite resuscitation

— Coagulopathy/DIC

— Concurrent severe preeclampsia/eclampsia, pulmonary edema, or sepsis

— Hematology: unclear etiology, hemoglobinopathy, hemolysis, transfusion-dependent disease, refractory anemia, planned IV iron in complex patients

— MFM: Hb <8 anytime, multiple gestation with anemia, sickle cell, thalassemia major, prior PPH

— Anesthesia: delivery planning when Hb <9 or high-risk transfusion scenario

— Nephrology: CKD-associated anemia

— Gastroenterology: refractory IDA, suspected GI bleeding (typically postpartum workup)

— Genetic counseling: any hemoglobinopathy or carrier status

— Hb ≥8, asymptomatic, no active bleeding

— Tolerating oral iron or accessing IV iron infusion center

— Adherent with follow-up; reliable transportation

— No fetal compromise on monitoring

CCS pearl: A 32-week G3P2 with Hb 6.8, dizziness, and reticulocytes 8% needs CCS orders: admit to L&D, IV access ×2, type & cross 2 units, CBC + retic + LDH + haptoglobin + DAT + smear, continuous fetal monitoring, OB and hematology consults, transfuse PRBC, advance to delivery planning if instability persists.

Admit immediately for:

ICU/L&D high-acuity triage:

Consultations:

Outpatient management appropriate when:

Key Differentials — Same-Category (Anemia Subtypes)

— Microcytic, hypochromic; high RDW; low ferritin (<30); low transferrin saturation; elevated TIBC

— Pica, restless legs, response to iron

— Microcytic with normal or elevated RBC count; Mentzer index <13; normal RDW; normal ferritin

— HbA2 elevated (β-trait) on electrophoresis; α-trait requires genetic testing

— No response to iron; do not iron-overload

— Normocytic (sometimes microcytic); normal-to-high ferritin, low iron, low TIBC, low transferrin saturation

— Underlying inflammation (autoimmune, chronic infection, malignancy)

— Hepcidin elevated

— Macrocytic, MCV often >110; hypersegmented neutrophils; oval macrocytes

— Neurologic symptoms distinguish from folate

— Elevated MMA and homocysteine; low B12

— Macrocytic; elevated homocysteine but normal MMA

— Common with poor diet, alcohol, antiepileptics, hemolysis

— No neurologic findings

— Elevated retic, LDH, indirect bilirubin; low haptoglobin

— Coombs-positive (autoimmune) vs Coombs-negative (G6PD, hereditary spherocytosis, PNH, sickle, MAHA)

— Sickled cells on smear; HbS on electrophoresis; chronic hemolysis with vaso-occlusion

— Pancytopenia, low reticulocytes; hypocellular marrow on biopsy

— Drug-induced (chloramphenicol, sulfa), viral (parvovirus, hepatitis), idiopathic

— Microcytic or dimorphic; high ferritin; ringed sideroblasts on marrow

— Lead, alcohol, isoniazid, congenital

Key distinction: Iron studies separate IDA, ACD, and thalassemia trait — ferritin low (IDA), ferritin high with low Fe and low TIBC (ACD), ferritin normal with normal Fe (thalassemia trait). This triad is heavily tested.

Iron deficiency anemia:

Thalassemia trait:

Anemia of chronic disease/inflammation:

B12 deficiency:

Folate deficiency:

Hemolytic anemias (general):

Sickle cell disease:

Aplastic anemia / bone marrow failure:

Sideroblastic anemia:

Key Differentials — Other-Category (Pregnancy-Specific and Mimics)

— Hb 10.5–11; normocytic; no symptoms; nadir 28–32 weeks

— Not pathologic — no workup or treatment needed

— Pregnancy plasma volume expansion drops Hct ~3–5 points — expected; check trimester-specific cutoffs

— Hemolysis, Elevated LFts, Low Platelets

— MAHA with schistocytes, elevated LDH, low haptoglobin

— Hypertension, RUQ pain, proteinuria

— Delivery is definitive treatment

— Anemia + thrombocytopenia + elevated transaminases + hypoglycemia + coagulopathy + hyperammonemia

— Swansea criteria

— Urgent delivery and supportive ICU care

— MAHA + thrombocytopenia + fever + neurologic symptoms + renal dysfunction

— ADAMTS13 <10% confirms; treat with plasma exchange, not delivery

— Renal failure predominant; complement dysregulation; eculizumab

— Placenta previa, abruption, ectopic, uterine rupture, PPH

— Acute drop in Hb with hemodynamic changes — resuscitate first, then workup

— GI bleed, trauma, ruptured ovarian cyst

— Hypothyroidism: macrocytic anemia, fatigue

— Addison's: normocytic anemia with hyperkalemia, hyponatremia, hyperpigmentation

— Methyldopa, penicillins → immune hemolysis

— Sulfa, nitrofurantoin, dapsone → oxidative hemolysis (G6PD)

— Trimethoprim, phenytoin, MTX → megaloblastic via folate antagonism

Board pearl: Schistocytes + thrombocytopenia in pregnancy = HELLP vs TTP vs AFLP vs aHUS — distinguish by BP, LFTs, glucose, ADAMTS13, and creatinine because management diverges sharply (delivery vs plasma exchange vs eculizumab).

Physiologic anemia of pregnancy:

Dilutional vs true anemia:

HELLP syndrome:

Acute fatty liver of pregnancy (AFLP):

TTP in pregnancy:

Postpartum HUS / atypical HUS:

Hemorrhage-related anemia:

Acute blood loss anemia (non-obstetric):

Endocrine mimics:

Drug-induced:

Secondary Prevention, Discharge Meds, and Long-Term Plan

— After Hb normalizes, continue oral iron 3 months to replenish stores

— Postpartum, especially after PPH or breastfeeding multiples: continue 6+ months

— Recheck ferritin at end of treatment — goal >50 ng/mL

— Standard PNV contains ~27 mg elemental iron and 0.4–1 mg folate — insufficient for treating IDA but adequate for prophylaxis

— Higher-iron PNVs or supplemental iron separate from PNV

— Folate 4 mg/day if prior NTD, on AEDs, or hemoglobinopathy

— Check at 6-week postpartum visit for all anemic patients

— Earlier (1–2 weeks) if PPH, transfusion, or severe anemia at delivery

— Oral iron, IV iron, B12, folate all safe during breastfeeding

— Maternal anemia → fatigue impairs lactation success; treat aggressively

— Counsel ≥18–24 months between pregnancies to allow iron replenishment

— Contraception counseling at postpartum visit; IUD or implant ideal for spacing

— Heavy menstrual bleeding before next pregnancy: workup with TVUS, consider OCPs, levonorgestrel IUD, endometrial evaluation

— Celiac, IBD: optimize before conception

— H. pylori: test and treat if recurrent IDA

— Post-bariatric: lifelong multivitamin + iron + B12 monitoring

— Influenza, Tdap, COVID-19 per CDC schedules

— Hemoglobinopathy carriers: partner testing, genetic counseling before next pregnancy

Step 3 management: Discharge orders after delivery with Hb 8.5 and PPH: ferrous sulfate 325 mg PO daily (or alternate-day) × 3 months, recheck CBC + ferritin at 6 weeks postpartum, contraception counseling for interpregnancy interval ≥18 months, lactation support referral.

Continue iron supplementation:

Prenatal vitamin selection:

Postpartum CBC:

Lactation considerations:

Interpregnancy interval:

Address upstream causes:

Vaccinations and labs:

Follow-Up, Monitoring, and Counseling

— Reticulocyte count at 1–2 weeks confirms marrow response

— CBC at 4 weeks — expect Hb rise ≥1 g/dL

— If no response: assess adherence, GI side effects, dosing schedule, ongoing blood loss, malabsorption, or alternate diagnosis

— Ferritin at end of repletion (~3 months) → goal >50

— CBC and reticulocyte at 2–4 weeks post-infusion

— Ferritin at 4–8 weeks; if persistent deficiency, repeat dose

— Phosphate at 2 weeks for repeat ferric carboxymaltose

— Repeat anemia screening at 28 weeks universally

— Growth ultrasound if Hb <9 sustained (IUGR screening) at 28 and 32–34 weeks

— Antenatal testing (NST/BPP) if Hb <8 or fetal concerns

— Day-of-discharge CBC if PPH or transfusion

— 6-week postpartum visit: CBC, screen for depression (EPDS), contraception, lactation

— Repeat at 3 months if still anemic

— Iron absorption tips: empty stomach, vitamin C, avoid milk/calcium/tea/coffee/antacids within 2 hours

— Expect dark stools (not melena); constipation manageable with stool softeners

— Adherence is the #1 reason for "treatment failure" — explore barriers

— Dietary sources: red meat, poultry, fish (heme iron); legumes, leafy greens, fortified cereals (non-heme)

— Avoid iron stored within reach of children — leading cause of pediatric poisoning death

— Address postpartum fatigue, depression screening at every visit through 12 months

— Exercise resumption guided by recovery, not Hb alone

Board pearl: A reticulocyte count that fails to rise within 2 weeks of oral iron suggests non-adherence, ongoing blood loss, malabsorption, or misdiagnosis — not insufficient dosing. Re-examine the case before escalating.

Oral iron monitoring:

IV iron monitoring:

Pregnancy-specific surveillance:

Postpartum:

Patient counseling:

Rehabilitation:

Ethical, Legal, and Patient Safety Considerations

— Discuss risks (TRALI, TACO, infection ~1:1–2 million, alloimmunization affecting future pregnancies), benefits, and alternatives (IV iron, ESAs, autologous donation, cell salvage)

— Jehovah's Witness patients: document specific products accepted/refused; engage hospital ethics committee preemptively; recognize a competent adult's refusal even when life-threatening

— In emergencies with incapacitated patient, transfuse under implied consent unless prior valid refusal document exists

— Most states allow minors to consent to prenatal care independently

— Confidentiality maintained around partner notification, social services involvement

— Mandatory reporting for suspected abuse or trafficking

— Use certified medical interpreters for consent discussions — family members are not appropriate for medical interpretation

— Recognize cultural practices around pregnancy nutrition (e.g., avoidance of certain foods affecting iron intake)

— Anemic patients discharged after delivery without iron prescription have 40% non-adherence; ensure medication in hand at discharge, not just on the printed list

— Postpartum follow-up appointment confirmed before discharge

— Closed-loop communication with primary care and OB for hemoglobinopathy carriers and ongoing iron therapy

— Two-patient identifiers before transfusion; bedside verification

— Iron poisoning in children — safe storage counseling at every prescription

— IV iron in infusion centers — emergency equipment available; monitor for Fishbane reaction

— Hemoglobinopathy carrier results have implications for partners, future pregnancies, and extended family — offer formal genetic counseling, respect non-directive approach

— Severe anemia may warrant work modifications under FMLA/ADA; document medical necessity

— Substance use causing anemia (e.g., alcohol-related folate deficiency) — supportive referral; reporting laws vary by state and pregnancy status

Step 3 management: A Jehovah's Witness at 36 weeks with Hb 7.5 requires aggressive IV iron, ESA initiation, tranexamic acid plan for delivery, anesthesia and ethics consults, and a clearly documented blood-product directive in the chart and the L&D handoff.

Informed consent for transfusion:

Pediatric/adolescent gravida:

Cultural and language access:

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

Patient safety:

Genetic counseling ethics:

Workplace and disability:

Mandatory reporting:

High-Yield Associations and Rapid-Fire Facts

Board pearl: When a stem says "pregnant, microcytic anemia, normal MCV/RBC ratio, no response to iron, Mediterranean ancestry" → think thalassemia trait — order hemoglobin electrophoresis, not more iron.

Trimester Hb cutoffs: 1st 11.0 / 2nd 10.5 / 3rd 11.0 / postpartum 10.0

Ferritin <30 ng/mL = iron deficiency in pregnancy (most sensitive single test)

Mentzer index <13 → thalassemia trait; >13 → IDA

High RDW + microcytic = IDA; normal RDW + microcytic = thalassemia

Alternate-day oral iron dosing improves absorption and tolerability (lower hepcidin)

Pica (ice = pagophagia) and restless legs → highly specific for iron deficiency

Vitamin C enhances non-heme iron absorption; calcium, tea, coffee, PPIs inhibit

B12 deficiency: hypersegmented neutrophils, neurologic findings, elevated MMA + homocysteine

Folate deficiency: macrocytic, elevated homocysteine only, no neuro findings

NEVER give folate alone if B12 deficiency possible — risks neurologic worsening

Folate 4 mg/day in: prior NTD, AED use, sickle cell, thalassemia, multiple gestation

Sickle cell pregnancy: folate 4–5 mg, stop hydroxyurea, no routine iron, hematology + MFM

HELLP: hemolysis + ↑LFTs + ↓platelets → delivery

TTP: ADAMTS13 <10% → plasma exchange (not delivery)

AFLP: anemia + thrombocytopenia + ↑LFTs + hypoglycemia + coagulopathy

Twin pregnancy: nearly doubled iron requirement — supplement prophylactically

Post-bariatric pregnancy: routinely deficient in iron, B12, folate, thiamine, D

IV iron preferred over oral when: Hb <9 in late pregnancy, oral intolerance/failure, malabsorption, near delivery

Ferric carboxymaltose → watch for hypophosphatemia

Tranexamic acid within 3 hours of PPH (WOMAN trial)

1 unit PRBC raises Hb ~1 g/dL

Goal Hb ≥11 entering labor; transfuse if <7 with symptoms

Interpregnancy interval ≥18 months prevents recurrent IDA

Postpartum depression risk is 1.5–3× higher with anemia

Universal hemoglobinopathy screening at first prenatal visit for at-risk ancestry

Continue iron 3 months after Hb normalizes to replenish stores

Board Question Stem Patterns

Key distinction: Step 3 stems will test the management pivot — when to switch from oral to IV iron, when to transfuse, when to deliver, when to consult. Identifying the correct next step, not the diagnosis, is the high-yield skill.

Stem 1 (Classic IDA): 28-week G2P1 with fatigue, Hb 9.8, MCV 72, RDW 17, ferritin 8, craves ice → Answer: oral ferrous sulfate, alternate-day dosing, recheck in 4 weeks.

Stem 2 (Thalassemia trait): 24-week G1 of Mediterranean ancestry with Hb 10.4, MCV 68, RBC 5.6, ferritin 80, no response to iron → Answer: hemoglobin electrophoresis (HbA2 elevated → β-thalassemia trait), offer partner screening.

Stem 3 (Late-pregnancy moderate anemia): 34-week patient, Hb 8.4, failed 6 weeks of oral iron, planned induction at 39 weeks → Answer: IV iron (e.g., ferric carboxymaltose or iron sucrose).

Stem 4 (Severe symptomatic anemia): 32-week, Hb 6.5, tachycardic, dyspneic → Answer: PRBC transfusion, admit, type & cross, fetal monitoring.

Stem 5 (B12 deficiency masked): Vegan G1 with Hb 9.5, MCV 112, paresthesias, low B12, normal folate → Answer: IM B12; folate alone would worsen neurologic disease.

Stem 6 (HELLP mimic): 36-week, BP 162/108, RUQ pain, Hb 9, platelets 75, AST 220, schistocytes → Answer: deliver.

Stem 7 (TTP): Pregnant patient, MAHA, thrombocytopenia, fever, neuro changes, creatinine bump, ADAMTS13 <10% → Answer: plasma exchange, NOT delivery.

Stem 8 (Sickle cell pregnancy): SCD G2P1 at 10 weeks on hydroxyurea → Answer: stop hydroxyurea, start folate 4 mg, hematology + MFM, update vaccines.

Stem 9 (Postpartum anemia): Day 2 postpartum after PPH, Hb 8.2, asymptomatic → Answer: oral iron 3 months, recheck at 6-week postpartum visit; consider IV iron if symptomatic.

Stem 10 (Jehovah's Witness): 28-week, Hb 8, refuses transfusion → Answer: IV iron + erythropoietin, document directive, anesthesia/ethics consults.

Stem 11 (Post-bariatric): Roux-en-Y patient at 16 weeks, Hb 8.7, MCV 84, low ferritin and low B12 → Answer: IV iron + parenteral B12 + folate; oral inadequate.

Stem 12 (Refractory IDA): Hb 9 despite 3 months oral iron, family history of celiac → Answer: tissue transglutaminase IgA, consider IV iron in interim.

One-Line Recap

Anemia in pregnancy is iron deficiency until proven otherwise; diagnose with ferritin <30, treat early with oral iron (alternate-day dosing preferred), escalate to IV iron when severe, late in pregnancy, or intolerant of oral, and transfuse only for hemodynamic instability or Hb <7 with symptoms — always confirming the underlying cause rather than treating the number alone.

Step 3 management: Anemia management in pregnancy is a longitudinal, multidisciplinary, ambulatory-to-inpatient continuum — the testable skill is knowing which pivot to make at which gestational age, and ensuring closed-loop follow-up at the 6-week postpartum visit to prevent recurrence in subsequent pregnancies.

Diagnosis: Trimester-specific Hb cutoffs (11/10.5/11); ferritin <30 = IDA; check MCV, RDW, reticulocytes, and peripheral smear; hemoglobin electrophoresis for unexplained microcytosis or at-risk ancestry.

First-line treatment: Oral ferrous sulfate (65 mg elemental) alternate-day with vitamin C on empty stomach; expect reticulocytosis at 1–2 weeks and Hb rise ≥1 g/dL at 4 weeks; continue 3 months after normalization.

Escalation: IV iron for Hb <9 in 2nd/3rd trimester, oral failure/intolerance, malabsorption, or late gestation; transfuse PRBC for Hb <7 with symptoms, active hemorrhage, or critical Hb <6; goal Hb ≥11 entering labor.

Don't miss: B12 deficiency (neurologic findings, never give folate alone), thalassemia trait (normal ferritin, high RBC, low Mentzer — don't iron-overload), hemoglobinopathies (folate 4 mg, hematology co-management), MAHA syndromes (HELLP/TTP/AFLP/aHUS — schistocytes demand emergent workup), and post-bariatric/CKD patients (need parenteral nutrients and ESAs).