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symptom.anemia-workup.v1PRODUCTION
symptom.anemia-workup.v1

Anemia symptom-triage (outpatient ddx + ED escalation for severe)

symptomchronicsubacuteundifferentiatedacuteadultgeriatricpregnancy
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Severity by Hgb (severe <7 or <8 cardiac → ED + transfusion; moderate 7-9.9 outpatient; mild 10-normal outpatient); MCV stratification (micro <80 / normo 80-100 / macro >100); retic index direction (hypo vs hyper-productive) (Camaschella NEJM 2015 PMID 32513860 verify)

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severity + MCV bucket stratified

Patient inputs (28)

Age shifts priors: pediatric → IDA from formula transition / prematurity; adolescent female → menstrual IDA; elderly → ACD / MDS / GI malignancy (Camaschella PMID 32513860 verify)

Sex shifts: pre-menopausal female → menstrual IDA + pregnancy; men + post-menopausal women with IDA → MUST workup occult GI malignancy (endoscopy + colonoscopy)

Pregnancy → physiologic dilution + iron/folate demand; Hgb thresholds <11 (1st/3rd tri) or <10.5 (2nd tri); avoid IV iron in 1st trimester

Melena, hematochezia, hematemesis, hematuria, menorrhagia, trauma, recent surgery, NSAIDs → blood-loss anemia; volume + chronicity drives workup

Vegan/vegetarian → B12 deficiency; alcohol → folate/B12/non-megaloblastic macrocytosis; malnutrition / post-bariatric → mixed deficiency

MTX, AZT, hydroxyurea, 5-FU, capecitabine → megaloblastic/non-megaloblastic macrocytosis; PPI → B12 malabsorption + IDA; NSAIDs → GI bleed; methyldopa/cefotetan/penicillin → drug AIHA

CKD → EPO-deficient anemia (route neph.ckd.core.v1); RA/IBD → ACD/AI; HIV/HCV → suppression; malignancy → ACD + chemo-induced + paraneoplastic

Hypotension + low Hgb + tachycardia → acute blood loss / hemodynamic compromise → ED + transfusion + cause workup

Tachycardia → severe anemia / acute blood loss / hemolysis; bradycardia → hypothyroidism contributor

Fatigue, dyspnea on exertion, pica (clay/ice), pallor, restless legs (IDA marker), glossitis (B12/iron), tachycardia, syncope → severity + cause clues

Severity by Hgb: severe <7 (or <8 cardiac) → ED + transfusion; moderate 7-9.9 → outpatient workup + monitor; mild 10-normal → outpatient workup (TRICC threshold)

MCV-anchored stratification: <80 microcytic (IDA/thal/ACD/sideroblastic/lead); 80-100 normocytic (ACD/early IDA/blood loss/hemolytic/aplastic/mixed/CKD); >100 macrocytic (megaloblastic vs non-megaloblastic)

Retic index <2 → hypoproductive (IDA, ACD, CKD, marrow failure, megaloblastic); retic index >3 → hyperproductive (hemolysis, acute blood loss with response); discriminates production vs destruction

CBC + differential + platelets + smear (spherocytes, schistocytes, bite cells, hypersegmented neut, blasts, target cells, sickle, basophilic stippling) — central diagnostic study

Ferritin <30 specific for IDA; TSAT <20 supports; high TIBC + low TSAT classic IDA; sTfR high in IDA + normal in ACD; sTfR/log(ferritin) >2 → IDA even with inflammation

B12 <200 deficient; B12 200-300 borderline → check MMA + homocysteine; MMA high + homocysteine high → B12 def; MMA normal + homocysteine high → folate def; B12 first ALWAYS before folate (Stabler PMID 22106456 verify)

Hemolysis labs: LDH high + haptoglobin low + indirect bili high + retic high → hemolysis; DAT (Coombs) positive → AIHA (warm IgG / cold IgM)

eGFR <60 → CKD anemia; EPO level if Hgb low + eGFR <60; iron repletion to TSAT >20, ferritin >100 before ESA; target Hgb 10-11.5 (not >13 — TREAT/CHOIR/CREATE trials)

Hb electrophoresis → thalassemia (Hb A2 elevated for beta-thal; alpha-thal needs DNA); Hb SS / SC / S-beta-thal → sickle cell (route heme.sickle-cell.core.v1)

G6PD deficiency screen if hemolysis + bite cells + Heinz bodies + drug/food trigger (fava, primaquine, dapsone, sulfa, rasburicase); WAIT 8 wk post-hemolysis for accurate level (young RBC have normal G6PD)

Pernicious anemia workup: anti-IF specific but insensitive; anti-parietal sensitive but nonspecific; Schilling test obsolete; B12 absorption studies if needed

Lead level if pediatric (paint, soil) or occupational (battery, plumber, smelter) + microcytic + basophilic stippling on smear

IDA in men + post-menopausal women → MANDATORY upper + lower endoscopy for occult bleed / CRC / celiac; capsule if negative endoscopy

BMBx if pancytopenia + unclear cause; MDS (dysplasia, ringed sideroblasts); aplastic (hypocellular); leukemia (blasts >20%); ITP/TTP exclusions

Mediterranean/Asian/African ancestry → thalassemia, hemoglobinopathies; sickle cell (African); HS autosomal dominant; G6PD X-linked Mediterranean/African/Asian male

Parvovirus B19 → transient aplastic crisis in HS/sickle; PRCA; Mycoplasma/EBV → cold agglutinin AIHA; HIV/CMV → various cytopenias

TSH high → hypothyroidism (non-megaloblastic macrocytosis); levothyroxine replacement typically normalizes Hgb

LFT + albumin → liver disease (macrocytosis from acanthocytes); hypersplenism with cirrhosis (route gi.cirrhosis.core.v1)

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Severity triggers (8)

8 need judgement
  • informationallife_threateningsevere_symptomatic_hgb_lt_7_or_lt_8_cardiac
    Hgb <7 + symptoms (chest pain, dyspnea, AMS, hypotension) OR Hgb <8 + cardiac disease — ED + STAT pRBC transfusion (TRICC threshold PMID 9971864 verify) + cause workup
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningttp_pentad_stat_plex
    Microangiopathic hemolytic anemia (schistocytes) + thrombocytopenia + neuro/renal/fever — TTP pentad; STAT plasma exchange (PLEX) — DO NOT delay for ADAMTS13; route heme.ttp.core.v1
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningacute_blood_loss_with_hemodynamic_compromise
    Acute Hgb drop + tachycardia/hypotension + melena/hematochezia/hematemesis/trauma — acute blood loss; ED + IVF + STAT pRBC transfusion + endoscopy + identify source; route gi.ugib.core.v1 / gi.lgib.core.v1
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebrisk_hemolysis_aiha_dat_positive
    Hgb low + retic high + LDH high + haptoglobin low + indirect bili high + DAT (Coombs) positive — autoimmune hemolytic anemia (AIHA); prednisone 1 mg/kg PO daily × 2-4 wk taper; IV methylpred if severe; rituximab if refractory; cold AIHA → keep WARM
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepancytopenia_leukemia_aplastic_workup
    Pancytopenia (low Hgb + low WBC + low plt) + smear (blasts → leukemia; hypocellular → aplastic) + BMBx — emergent hematology; route heme.acute-leukemia.core.v1 if blasts; aplastic anemia → IST or HSCT; PRCA → IVIG / thymectomy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepernicious_anemia_b12_before_folate_KEY_SAFETY
    Megaloblastic anemia (MCV >100 + hypersegmented neut + macro-ovalocytes) — ALWAYS start B12 BEFORE folate (folate alone in B12 deficiency precipitates subacute combined degeneration of cord — irreversible neurologic); cyanocobalamin 1000 mcg IM weekly × 8 then monthly OR 1000-2000 mcg PO daily; check anti-IF + anti-parietal for pernicious anemia (Stabler NEJM 2013 PMID 22106456 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereida_in_men_or_post_meno_women_mandate_gi_workup
    IDA in adult male OR post-menopausal female — MANDATORY upper + lower endoscopy (occult GI bleed, colorectal cancer, celiac); capsule endoscopy if both negative; assume malignancy until proven otherwise (BSH 2021 PMID 30303080 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateckd_anemia_esa_target_hgb_10_to_11_5
    CKD (eGFR <60) + low Hgb + low retic + low EPO → ESA (epoetin/darbepoetin) when Hgb <10 + iron sufficient (TSAT >20%, ferritin >100); target Hgb 10-11.5 NOT >13 (TREAT/CHOIR/CREATE — increased CV/stroke/mortality at higher targets); route neph.ckd.core.v1
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

outpatient playbook — drug actions (12)

  1. 1. ferrous sulfate (oral iron — IDA first-line)
    325 mg (65 mg elemental) PO every other day (QOD) • PO • QOD
    trigger: IDA confirmed (low ferritin <30, low TSAT, high TIBC, microcytic)
    Stoffel 2017 PMID 26627933 verify — QOD better tolerated (less GI sx) + equivalent absorption vs daily (down-regulated hepcidin after 24h). Continue × 3-6 months past ferritin normalization to replete stores.
  2. 2. ferric carboxymaltose (IV iron — IDA refractory/intolerant)
    750 mg IV × 2 (1500 mg total) over ≥15 min separated by ≥7 days • IV • q7d × 2
    trigger: IDA + PO intolerance OR refractory (Hgb non-response at 4 wk) OR severe (Hgb <8) OR pregnancy 2nd/3rd tri OR CKD/dialysis
    IV iron rapid repletion; monitor hypophosphatemia (ferric carboxymaltose) + anaphylaxis (test dose for iron dextran; less common with carboxymaltose); avoid 1st-trimester pregnancy
  3. 3. cyanocobalamin (B12 — megaloblastic/pernicious)
    1000 mcg IM weekly × 8 weeks then monthly indefinitely OR 1000-2000 mcg PO daily • IM or PO • weekly → monthly OR daily
    trigger: B12 deficiency confirmed (B12 <200 or borderline + high MMA + high homocysteine + megaloblastic features)
    Stabler NEJM 2013 PMID 22106456 verify — Vidal-Alaball Cochrane 2005 shows PO equally effective for pernicious anemia (1% absorption via passive diffusion sufficient); IM faster recovery in severe/neuro; LIFELONG replacement for pernicious anemia
  4. 4. folic acid (folate deficiency)
    1-5 mg PO daily • PO • daily
    trigger: Folate deficiency confirmed (low folate + normal MMA + high homocysteine + B12 EXCLUDED first)
    CRITICAL: ALWAYS start B12 BEFORE folate in unclear megaloblastic — folate alone in B12 deficiency precipitates subacute combined degeneration of cord (irreversible neurologic)
  5. 5. epoetin alfa (CKD anemia)
    50-100 U/kg SC 3x/week • SC • 3x/week
    trigger: CKD (eGFR <60) + Hgb <10 + iron sufficient (TSAT >20%, ferritin >100) — KDIGO 2012
    Replete iron FIRST (TSAT >20, ferritin >100); target Hgb 10-11.5 NOT >13 (TREAT PMID 19880844 verify, CHOIR PMID 17108342 verify, CREATE PMID 17108343 verify — increased CV/stroke at higher targets); titrate by 25% q4 wk
  6. 6. darbepoetin alfa (CKD anemia — longer half-life)
    0.45 mcg/kg SC weekly • SC • weekly
    trigger: Alternative to epoetin; preference for q1-2 week dosing
    Same target Hgb 10-11.5; same boxed warning (CV / stroke / tumor progression); dose-adjust based on response
  7. 7. prednisone (AIHA first-line)
    1 mg/kg PO daily × 2-4 weeks then taper over 3-6 months • PO • daily then taper
    trigger: Warm AIHA (DAT+ IgG ± C3) with hemolysis confirmed; severe → IV methylprednisolone
    Warm AIHA — 70-85% respond; PCP/Strongyloides screen before high-dose steroids; bone protection; gastric protection; taper slowly; relapse common
  8. 8. rituximab (AIHA refractory)
    375 mg/m2 IV weekly × 4 doses • IV • weekly × 4
    trigger: AIHA refractory to steroids OR steroid-dependent OR contraindication to long steroids
    Anti-CD20; effective in warm AND cold AIHA; screen HBV/HCV/HIV/TB before; IVIG concurrent if life-threatening
  9. 9. IVIG (PRCA from parvovirus, life-threatening hemolysis bridge)
    400 mg/kg/day × 5 days (PRCA) or 1-2 g/kg over 2-5 days (bridge) • IV • daily × 2-5
    trigger: Pure red cell aplasia from parvovirus B19 (immunocompromised); life-threatening hemolysis bridging definitive treatment
    PRCA: parvovirus-specific; thymoma → thymectomy; drug-induced → stop drug + IVIG; pre-medicate (acetaminophen + diphenhydramine)
  10. 10. transfusion (severe symptomatic anemia)
    1-2 units PRBC; recheck Hgb 4-6 h post; goal Hgb >7 (or >8 cardiac dz) • IV • one-time then reassess
    trigger: Hgb <7 + symptoms (chest pain, dyspnea, AMS, hypotension) OR Hgb <8 + cardiac disease OR acute blood loss with hemodynamic instability
    TRICC PMID 9971864 verify — restrictive (Hgb 7) non-inferior to liberal (Hgb 10) for most ICU patients; risk hyperkalemia in massive transfusion; warm IVF; AVOID over-transfusion in chronic stable anemia
  11. 11. discontinue offending drug (drug-induced)
    N/A • medication management • one-time
    trigger: Drug-induced anemia (methyldopa AIHA, cefotetan/ceftriaxone/penicillin AIHA; MTX/AZT/hydroxyurea macrocytic; PPI B12; NSAID GI bleed; chemo cytopenia)
    Critical step; substitute non-offending agent; counsel future avoidance; monitor for recovery (4-12 wk for AIHA; 8-12 wk for macrocytosis)
  12. 12. AVOID empiric folate in unclear megaloblastic (KEY SAFETY)
    N/A • medication management • one-time
    trigger: Megaloblastic anemia with B12 status unclear
    CRITICAL SAFETY RULE — folate alone in B12 deficiency precipitates SCD myelopathy (irreversible); check B12 first; treat B12 first; add folate AFTER B12 normalizes if folate also deficient

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: MCV <80 + low ferritin (<30) + low TSAT + high TIBC + high sTfR — iron-deficiency anemia (IDA); oral ferrous sulfate 325 mg QOD (better tolerated) or IV iron if refractory/intolerant; men + post-menopausal women MUST get GI evaluation for occult bleeding/malignancy (Camaschella NEJM 2015 PMID 32513860 verify; BSH iron 2021 PMID 30303080 verify); MCV <80 + Mentzer <13 + normal iron studies + family hx Mediterranean/Asian/African — thalassemia trait (alpha/beta); confirm Hb electrophoresis; no iron unless concurrent IDA; genetic counseling for partner screen; MCV <80-95 + chronic inflammation (RA, IBD, CKD, malignancy) + normal/high ferritin + low TSAT + sTfR/log(ferritin) <1 — anemia of chronic disease/inflammation (ACD/AI); treat underlying; ESA if CKD + Hgb <10.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Anemia symptom-triage (outpatient ddx + ED escalation for severe)** (symptom.anemia-workup.v1).
Phenotype framing: Microcytic: IDA, thalassemia, ACD (late), sideroblastic, lead. Normocytic: ACD, early IDA, acute blood loss, hemolytic (AIHA + intrinsic), aplastic, mixed, CKD. Macrocytic megaloblastic: B12, folate, pernicious, MTHFR, drug. Macrocytic non-megaloblastic: alcohol, liver, hypothyroid, MDS. Hemolytic: AIHA (warm IgG / cold IgM), HS, G6PD, sickle, thalassemia, TTP, DIC, drug-induced. Marrow failure: PRCA, aplastic. Special: pregnancy, peds, acute blood loss.
Scope: Severity by Hgb (severe <7 or <8 cardiac → ED + transfusion; moderate 7-9.9 outpatient; mild 10-normal outpatient); MCV stratification (micro <80 / normo 80-100 / macro >100); retic index direction (hypo vs hyper-productive) (Camaschella NEJM 2015 PMID 32513860 verify)

No severity triggers fired against current inputs.

Plan

No regimen axis selected (engine has no regimen_axes or could not match).

Setting playbook (outpatient) — MCV-anchored + retic-anchored anemia ddx + cause-specific treatment (IDA oral/IV iron, B12 IM/PO, folate PO, ACD treat-underlying, CKD ESA, AIHA steroids) + downstream routing (sickle, leukemia, TTP, CKD, GI bleed); men + post-menopausal women with IDA → MANDATORY GI workup; ALWAYS B12 before folate to avoid SCD myelopathy (Camaschella NEJM 2015 PMID 32513860 verify; Stabler NEJM 2013 PMID 22106456 verify; BSH iron 2021 PMID 30303080 verify)
1. ferrous sulfate (oral iron — IDA first-line) 325 mg (65 mg elemental) PO every other day (QOD) PO QOD — IDA confirmed (low ferritin <30, low TSAT, high TIBC, microcytic) (Stoffel 2017 PMID 26627933 verify — QOD better tolerated (less GI sx) + equivalent absorption vs daily (down-regulated hepcidin after 24h). Continue × 3-6 months past ferritin normalization to replete stores.)
2. ferric carboxymaltose (IV iron — IDA refractory/intolerant) 750 mg IV × 2 (1500 mg total) over ≥15 min separated by ≥7 days IV q7d × 2 — IDA + PO intolerance OR refractory (Hgb non-response at 4 wk) OR severe (Hgb <8) OR pregnancy 2nd/3rd tri OR CKD/dialysis (IV iron rapid repletion; monitor hypophosphatemia (ferric carboxymaltose) + anaphylaxis (test dose for iron dextran; less common with carboxymaltose); avoid 1st-trimester pregnancy)
3. cyanocobalamin (B12 — megaloblastic/pernicious) 1000 mcg IM weekly × 8 weeks then monthly indefinitely OR 1000-2000 mcg PO daily IM or PO weekly → monthly OR daily — B12 deficiency confirmed (B12 <200 or borderline + high MMA + high homocysteine + megaloblastic features) (Stabler NEJM 2013 PMID 22106456 verify — Vidal-Alaball Cochrane 2005 shows PO equally effective for pernicious anemia (1% absorption via passive diffusion sufficient); IM faster recovery in severe/neuro; LIFELONG replacement for pernicious anemia)
4. folic acid (folate deficiency) 1-5 mg PO daily PO daily — Folate deficiency confirmed (low folate + normal MMA + high homocysteine + B12 EXCLUDED first) (CRITICAL: ALWAYS start B12 BEFORE folate in unclear megaloblastic — folate alone in B12 deficiency precipitates subacute combined degeneration of cord (irreversible neurologic))
5. epoetin alfa (CKD anemia) 50-100 U/kg SC 3x/week SC 3x/week — CKD (eGFR <60) + Hgb <10 + iron sufficient (TSAT >20%, ferritin >100) — KDIGO 2012 (Replete iron FIRST (TSAT >20, ferritin >100); target Hgb 10-11.5 NOT >13 (TREAT PMID 19880844 verify, CHOIR PMID 17108342 verify, CREATE PMID 17108343 verify — increased CV/stroke at higher targets); titrate by 25% q4 wk)
6. darbepoetin alfa (CKD anemia — longer half-life) 0.45 mcg/kg SC weekly SC weekly — Alternative to epoetin; preference for q1-2 week dosing (Same target Hgb 10-11.5; same boxed warning (CV / stroke / tumor progression); dose-adjust based on response)
7. prednisone (AIHA first-line) 1 mg/kg PO daily × 2-4 weeks then taper over 3-6 months PO daily then taper — Warm AIHA (DAT+ IgG ± C3) with hemolysis confirmed; severe → IV methylprednisolone (Warm AIHA — 70-85% respond; PCP/Strongyloides screen before high-dose steroids; bone protection; gastric protection; taper slowly; relapse common)
8. rituximab (AIHA refractory) 375 mg/m2 IV weekly × 4 doses IV weekly × 4 — AIHA refractory to steroids OR steroid-dependent OR contraindication to long steroids (Anti-CD20; effective in warm AND cold AIHA; screen HBV/HCV/HIV/TB before; IVIG concurrent if life-threatening)
9. IVIG (PRCA from parvovirus, life-threatening hemolysis bridge) 400 mg/kg/day × 5 days (PRCA) or 1-2 g/kg over 2-5 days (bridge) IV daily × 2-5 — Pure red cell aplasia from parvovirus B19 (immunocompromised); life-threatening hemolysis bridging definitive treatment (PRCA: parvovirus-specific; thymoma → thymectomy; drug-induced → stop drug + IVIG; pre-medicate (acetaminophen + diphenhydramine))
10. transfusion (severe symptomatic anemia) 1-2 units PRBC; recheck Hgb 4-6 h post; goal Hgb >7 (or >8 cardiac dz) IV one-time then reassess — Hgb <7 + symptoms (chest pain, dyspnea, AMS, hypotension) OR Hgb <8 + cardiac disease OR acute blood loss with hemodynamic instability (TRICC PMID 9971864 verify — restrictive (Hgb 7) non-inferior to liberal (Hgb 10) for most ICU patients; risk hyperkalemia in massive transfusion; warm IVF; AVOID over-transfusion in chronic stable anemia)
11. discontinue offending drug (drug-induced) N/A medication management one-time — Drug-induced anemia (methyldopa AIHA, cefotetan/ceftriaxone/penicillin AIHA; MTX/AZT/hydroxyurea macrocytic; PPI B12; NSAID GI bleed; chemo cytopenia) (Critical step; substitute non-offending agent; counsel future avoidance; monitor for recovery (4-12 wk for AIHA; 8-12 wk for macrocytosis))
12. AVOID empiric folate in unclear megaloblastic (KEY SAFETY) N/A medication management one-time — Megaloblastic anemia with B12 status unclear (CRITICAL SAFETY RULE — folate alone in B12 deficiency precipitates SCD myelopathy (irreversible); check B12 first; treat B12 first; add folate AFTER B12 normalizes if folate also deficient)

Non-pharmacologic actions:
- Dietary counseling: iron-rich foods (meat, beans, fortified cereal); vitamin C with iron; AVOID tea/coffee with iron
- Pregnancy supplementation: prenatal vitamin + folic acid 400-800 mcg + iron 30-60 mg elemental daily
- Deprescribe / substitute offending medication (PPI, NSAID, MTX, methyldopa)
- GI workup for IDA in men + post-menopausal women: upper + lower endoscopy + capsule if negative
- Hematology consult: refractory IDA, hemolytic, pancytopenia, MDS suspicion, hemoglobinopathy, PRCA
- Genetic counseling: thalassemia, sickle, HS, G6PD — partner screen
- Pregnancy: maternal-fetal medicine if severe / refractory
- Nephrology consult: CKD anemia + ESA initiation
- Endocrinology consult: pernicious anemia + autoimmune polyendocrine screen
- Avoid trigger exposures: G6PD avoid fava, primaquine, dapsone, sulfa, rasburicase, naphthalene
- Cold AIHA: keep warm (avoid cold exposure → hemolysis); discontinue cold cardioplegia
- PCP/Strongyloides screen before high-dose steroids
- Bone protection (Ca + Vit D + bisphosphonate) for chronic steroids; gastric protection

Monitoring

Setting (outpatient) monitoring:
- CBC + retic at 2-4 weeks after iron initiation (expect retic surge by week 1; Hgb rise 1-2 g/dL by 4 wk)
- Ferritin at 8-12 weeks (target >50 general OR >100 CKD; continue iron 3-6 months past normalization)
- B12 + MMA + homocysteine: B12 within days normalizes; MMA + homocysteine + neuro recovery weeks-months
- CKD anemia: Hgb q4 weeks; titrate ESA by 25%; target 10-11.5 NOT >13
- AIHA: CBC + retic + LDH + haptoglobin + bili + DAT weekly until response; steroid taper carefully
- Smear review for hemoglobinopathies / MDS evolution
- Endoscopy yield: men + post-menopausal women — colonoscopy + upper endoscopy

Follow-up plan: Hematology referral for refractory / hemolytic / pancytopenia / MDS / hemoglobinopathy. GI for IDA + occult blood loss workup (men + post-menopausal women → endoscopy + colonoscopy; capsule if negative). Dietitian for vegan / alcohol / malnutrition / pregnancy. Pregnancy nutrition + iron supplementation. Chronic CKD / RA / IBD optimization (route neph.ckd.core.v1). Genetic counseling for thalassemia / sickle / HS. Recurrence prevention (deprescribe NSAID/PPI if drug-induced); dietary counseling; partner thalassemia screen.
- Close-out criterion: long-term plan in place + follow-up scheduled

Monitoring phase: CBC + retic at 2-4 weeks (response check; expect retic surge by week 1 in IDA on iron); ferritin at 8-12 weeks (target normalization >50 general or >100 CKD); B12 / MMA + homocysteine + neuro recovery; CKD anemia Hgb target 10-11.5 (NOT >13); transfusion threshold Hgb 7 (8 cardiac) — TRICC; ESA dose titration q4 weeks

Disposition

Current setting: outpatient — MCV-anchored + retic-anchored anemia ddx + cause-specific treatment (IDA oral/IV iron, B12 IM/PO, folate PO, ACD treat-underlying, CKD ESA, AIHA steroids) + downstream routing (sickle, leukemia, TTP, CKD, GI bleed); men + post-menopausal women with IDA → MANDATORY GI workup; ALWAYS B12 before folate to avoid SCD myelopathy (Camaschella NEJM 2015 PMID 32513860 verify; Stabler NEJM 2013 PMID 22106456 verify; BSH iron 2021 PMID 30303080 verify)

Disposition criteria:
- Continue outpatient: chronic stable mild-moderate anemia + cause identified + responsive
- ED escalation: severe symptomatic + brisk hemolysis + TTP + pancytopenia + acute blood loss
- Inpatient: severe IDA needing IV iron + workup; new AIHA on steroids; CKD anemia inpatient stabilization
- Telemetry: hemodynamic monitoring during transfusion; rapid hemolysis
- ICU: severe symptomatic + hemodynamic compromise; TTP on PLEX
- Route to: heme.sickle-cell.core.v1; heme.acute-leukemia.core.v1; neph.ckd.core.v1; heme.ttp.core.v1; heme.dic.v1; gi.ugib.core.v1; gi.cirrhosis.core.v1

Escalation triggers (move to higher acuity):
- Hgb <7 + symptoms (chest pain, dyspnea, AMS, hypotension) → ED + transfusion
- Hgb <8 + cardiac disease → ED + transfusion + cardiology consult
- Brisk hemolysis with hemodynamic instability → ED + transfusion + ICU monitoring
- TTP pentad (MAHA + thrombocytopenia + neuro/renal/fever) → STAT PLEX (route heme.ttp.core.v1)
- DIC features (coag + thrombocytopenia + bleeding/thrombosis) → route heme.dic.v1
- Pancytopenia + blasts on smear → STAT hematology + BMBx + route heme.acute-leukemia.core.v1
- Acute GI bleed → ED + endoscopy (route gi.ugib.core.v1)
- Severe AIHA (Hgb <6 + ongoing hemolysis) → admit + IV steroid + ?IVIG bridge
- Refractory IDA to PO iron at 4 wk → IV iron OR GI workup
- CKD anemia + Hgb >13 on ESA → reduce ESA + reassess target
- IV iron anaphylaxis / severe hypersensitivity → stop infusion + epinephrine + supportive + report
- IV iron hypophosphatemia (ferric carboxymaltose) symptomatic → phosphate repletion + monitoring
- Sickle cell crisis confirmed → route heme.sickle-cell.core.v1

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Hgb <7 + symptoms (chest pain, dyspnea, AMS, hypotension) OR Hgb <8 + cardiac disease — ED + STAT pRBC transfusion (TRICC threshold PMID 9971864 verify) + cause workup
- [LIFE_THREATENING] Microangiopathic hemolytic anemia (schistocytes) + thrombocytopenia + neuro/renal/fever — TTP pentad; STAT plasma exchange (PLEX) — DO NOT delay for ADAMTS13; route heme.ttp.core.v1
- [LIFE_THREATENING] Acute Hgb drop + tachycardia/hypotension + melena/hematochezia/hematemesis/trauma — acute blood loss; ED + IVF + STAT pRBC transfusion + endoscopy + identify source; route gi.ugib.core.v1 / gi.lgib.core.v1

Citations

- 2015 Camaschella iron NEJM + 2013 Stabler B12 NEJM + 2021 BSH iron + KDIGO 2012 anemia of CKD + TRICC transfusion + ASH AIHA/PRCA/TTP guidelines [PMID:36827619](https://pubmed.ncbi.nlm.nih.gov/36827619/)
- Cited evidence (PMID 17375513) [PMID:17375513](https://pubmed.ncbi.nlm.nih.gov/17375513/)

Last reconciled with current guidelines: 2026-05-31.
References
  • 2015 Camaschella iron NEJM + 2013 Stabler B12 NEJM + 2021 BSH iron + KDIGO 2012 anemia of CKD + TRICC transfusion + ASH AIHA/PRCA/TTP guidelines — PMID:36827619
  • Cited evidence (PMID 17375513) — PMID:17375513