12-phase flow (12)

1. 1FRAME
   Frame the case: confirmed/suspected IDA in adult vs pediatric vs pregnancy; chronic outpatient repletion vs symptomatic anaemia vs anaemia secondary to active GI bleeding. IDA is a SYMPTOM — the engine commits up-front to a mandatory source-of-loss search (BSG 2021 PMID 34497146; AGA 2020 PMID 32810434).
   inputs: age, sex, pregnancy_status
   advance: Population + scenario (chronic vs symptomatic vs bleeding) assigned
2. 2ENTRY
   Trigger: low Hb / microcytosis / low ferritin on labs, iron-deficiency symptom cluster (fatigue, exertional dyspnoea, pica, restless legs), or IDA on the problem list for repletion follow-up.
   inputs: cbc_with_indices
   advance: Entry trigger characterised
3. 3CONTEXT
   Capture age/sex/pregnancy, menstrual history, GI symptoms, NSAID/anticoagulant use, diet (vegan/vegetarian), malabsorption history (coeliac, bariatric, IBD, atrophic gastritis, H. pylori), prior endoscopy, blood-donation, CKD/HF comorbidity. Context decides the source-evaluation pathway and oral-vs-IV route.
   inputs: age, sex, pregnancy_status, gi_symptoms, menstrual_history, nsaid_anticoagulant_use, malabsorption_history
   advance: History sufficient to choose source pathway
4. 4RED_FLAGS
   Bayesian pivots. (1) ACTIVE-BLEED pivot: melaena/haematemesis/haematochezia + haemodynamic compromise → this is acute GI bleeding, NOT chronic IDA — route to gi.ugib.core.v1 / gi.lgib.core.v1 and resuscitate first. (2) MALIGNANCY pivot: IDA in a man or post-menopausal woman without an obvious source carries a ~5-15% colorectal-cancer yield on colonoscopy (AGA 2020 PMID 32810434) — bidirectional endoscopy is mandatory, not optional. (3) Symptomatic severe anaemia (Hb <7, or <8 with cardiac disease, angina, syncope, decompensated HF) → restrictive transfusion per AABB 2023 (PMID 37824153) AND treat the deficit. (4) Pregnancy with severe anaemia near term → expedite (IV iron / transfusion planning for delivery). (5) Pica + restless-leg syndrome flags profound depletion warranting prompt repletion.
   inputs: cbc_with_indices, gi_symptoms
   actions: workup.ugib
   advance: Emergent bleeding/transfusion need excluded or routed
5. 5INITIAL_WORKUP
   CBC with indices (microcytic hypochromic, MCV <80, ↑RDW), ferritin, TSAT/transferrin, serum iron, CRP, peripheral smear. Diagnostic anchor: ferritin <30 ng/mL = absolute iron deficiency (BSG 2021); <15 highly specific (LR+ ≈ 50). When CRP elevated or CKD present, do not exclude IDA on a "normal" ferritin — use TSAT <20% + ferritin <100 (KDIGO 2026).
   inputs: cbc_with_indices, ferritin, transferrin_saturation, crp
   actions: panel.cbc, panel.iron, panel.inflammation
   advance: Iron-deficiency confirmed or reframed
6. 6BRANCHING_WORKUP
   MANDATORY source-of-loss search, branched by population. Men + post-menopausal women: bidirectional endoscopy (OGD + colonoscopy) to exclude GI malignancy (~5-15% CRC yield; AGA 2020 PMID 32810434), duodenal biopsy for coeliac. Pre-menopausal women: quantify menstrual loss + coeliac serology (anti-tTG) ± pregnancy; endoscopy if GI symptoms, ≥50 y, family CRC history, or refractory. All: coeliac serology, H. pylori testing, urinalysis (renal-tract loss), reticulocyte-Hb to confirm functional deficiency. sTfR / sTfR-ferritin index when ACD vs IDA remains ambiguous. Capsule endoscopy if bidirectional endoscopy negative + ongoing transfusion-dependent loss.
   inputs: gi_symptoms, menstrual_history, reticulocyte_hemoglobin, malabsorption_history
   actions: workup.chronic_ida, workup.colorectal_screening, workup.ugib
   advance: Source identified OR documented bidirectional-endoscopy-negative
7. 7DIFFERENTIAL
   Terminal pattern + cause: absolute IDA from GI occult loss (peptic ulcer, colorectal neoplasm, angiodysplasia, oesophagitis), menstrual/gynaecologic loss, malabsorption (coeliac, bariatric, atrophic gastritis, H. pylori, IBD), dietary insufficiency (infants/vegan), increased demand (pregnancy/growth), intravascular loss (mechanical valve, runner haematuria). Discriminate from anaemia of chronic disease (ferritin normal/high, TSAT low, CRP up, sTfR-F index low), thalassaemia trait (low MCV but NORMAL/low RDW, Mentzer index <13, normal/raised ferritin — do not iron-load), sideroblastic and lead.
   inputs: ferritin, transferrin_saturation
   advance: Cause + IDA-vs-mimic resolved
8. 8RISK_STRATIFICATION
   Stratify severity (Hb tier), symptom burden (QoL/fatigue — PHQ-9 surfaces overlapping depressive-fatigue), comorbidity that mandates IV iron (CKD by eGFR, HF, IBD, post-bariatric, 2nd/3rd-trimester pregnancy), and red-flag cause (malignancy). eGFR (CKD-EPI 2021) reframes monitoring thresholds and routes CKD-anaemia to neph.ckd.core.v1 (KDIGO 2026).
   inputs: cbc_with_indices, creatinine_egfr
   actions: calc.ckd_epi_2021, calc.phq9
   advance: Severity + route (oral vs IV) + cause-driven referrals set
9. 9TREATMENT
   Repletion + treat the cause. ORAL first-line in most: elemental iron ~40-60 mg (e.g., ferrous sulfate 325 mg = 65 mg elemental) as a single morning dose on ALTERNATE DAYS — Stoffel showed alternate-day single-dose maximises fractional absorption and roughly halves GI side-effects vs split daily dosing because each dose transiently raises hepcidin and blunts the next-day dose (Lancet Haematol 2017 PMID 29032957; Blood 2020 PMID 31413088). Expected Hb rise ~1 g/dL at 2 wk and ~2 g/dL by 3-4 wk; continue 3 months AFTER Hb normalises to replenish stores (target ferritin >100). IV iron when oral intolerant/failed, malabsorption, CKD, IBD, 2nd/3rd-trimester pregnancy, post-bariatric, or ongoing loss outpacing oral: ferric derisomaltose or ferric carboxymaltose (single high-dose), ferumoxytol, or iron sucrose — total-dose by Ganzoni/simplified table. FCM has a strong hypophosphataemia signal (Wolf JAMA 2020: 75% vs 8% with FDI, PMID 32016310) — check phosphate if repeat dosing/symptoms. FERWON-IDA: FDI gives faster haematologic response vs iron sucrose with low serious-hypersensitivity rate (PMID 31243803). Transfusion only for symptomatic/unstable anaemia, restrictive Hb 7 (8 with cardiac disease) per AABB 2023 (PMID 37824153) — transfusion does NOT treat iron deficiency. In HF with iron deficiency, IV FCM/FDI improves outcomes even without anaemia (AFFIRM-AHF PMID 33197395; IRONMAN PMID 36347265) — route to cardio.hf.core.v1.
   inputs: ferritin, transferrin_saturation, pregnancy_status
   actions: workup.chronic_ida
   advance: Repletion route chosen + cause-directed treatment / referral initiated
10. 10DISPOSITION
    Outpatient for the large majority (oral iron + scheduled source workup). Day-unit/infusion centre for IV iron. ED/inpatient for symptomatic severe anaemia, haemodynamic instability, or active GI bleeding (then route to gi.ugib/gi.lgib). Refer: GI for endoscopy/positive source, gynaecology for HMB, dietitian for dietary cause, and the relevant comorbidity engine (CKD/HF/IBD).
    inputs: cbc_with_indices
    advance: Disposition + referrals set
11. 11MONITORING
    Recheck Hb + reticulocytes at 2-4 weeks (expected Hb ↑ ~1 g/dL by 2 wk, ~2 g/dL by 3-4 wk) — a flat response signals non-adherence, continued loss, malabsorption, wrong diagnosis (thalassaemia/ACD), or need for IV iron. After Hb normal, check ferritin/TSAT to confirm store repletion (target ferritin >100); continue oral iron 3 months beyond. Post-IV-iron: reassess Hb + iron indices at 4-8 weeks; check phosphate after FCM if symptomatic/repeat dosing. CKD: TSAT/ferritin trends per KDIGO 2026; eGFR (CKD-EPI 2021) drives the threshold.
    inputs: cbc_with_indices, ferritin, transferrin_saturation
    actions: panel.cbc, panel.iron, calc.ckd_epi_2021
    advance: Response trajectory documented
12. 12FOLLOWUP
    Confirm source addressed (endoscopy result actioned, HMB managed, coeliac on gluten-free, H. pylori eradicated). Surveillance for recurrence (annual CBC ± ferritin in ongoing-risk patients), dietary counselling, vitamin-C co-administration tip, return precautions (recurrent fatigue, melaena, fresh PR bleeding). Pregnancy: confirm repletion before delivery and plan postpartum recheck. Pediatrics: re-screen at-risk infants/toddlers per schedule.
    inputs: ferritin
    advance: Cause addressed + surveillance plan documented