12-phase flow (12)

1. 1FRAME
   Frame the patient as chronic normocytic anaemia in the context of systemic inflammation / chronic disease; the engine’s job is to (a) confirm an inflammatory mechanism, (b) decide whether absolute or functional iron deficiency coexists, (c) identify and treat the underlying disease (Weiss NEJM 2019 PMID 31532961)
   inputs: underlying_inflammatory_disease, age
   advance: Anaemia confirmed chronic and inflammatory context identified
2. 2ENTRY
   Triggered by low Hb on routine labs, the high-ferritin/low-TSAT iron-study pattern, anaemia in a known CKD/RA/SLE/IBD/cancer/HF patient, or symptomatic fatigue/dyspnoea (Weiss NEJM 2005 PMID 15758012)
   inputs: 718-7
   actions: panel.cbc
   advance: Anaemia entry confirmed and chronicity established
3. 3CONTEXT
   Capture the underlying disease (CKD stage via eGFR, RA/SLE/IBD activity, chronic infection, malignancy, HF, obesity-inflammation, ageing), bleeding/menstrual history, medications (PPIs, ACEi/ARB, immunosuppression, chemotherapy, ESA, iron), prior transfusions, baseline Hb, frailty (KDIGO 2026; Weiss NEJM 2019 PMID 31532961)
   inputs: underlying_inflammatory_disease, age, 20570-8, 2823-3
   actions: panel.cmp, calc.ckd_epi_2021
   advance: Underlying disease, CKD stage, and reversible contributors documented
4. 4RED_FLAGS
   Symptomatic anaemia (angina / decompensated HF / syncope / Hb critically low) → urgent restrictive transfusion (AABB 2023 PMID 37824153). New unexplained anaemia in an elderly patient → occult GI malignancy / MDS / myeloma workup BEFORE attributing to chronic disease. Brisk Hb fall or melaena → acute bleeding source (the inflammatory label must never mask a treatable bleed). Pancytopenia / blasts / dysplastic indices → marrow pathology (Weiss NEJM 2019 PMID 31532961)
   inputs: 718-7, age
   actions: workup.chronic_ida
   advance: Emergencies excluded or stabilised
5. 5INITIAL_WORKUP
   CBC + indices + reticulocyte count (inappropriately low retic supports hypoproliferative ACD); peripheral smear; iron panel (ferritin, TSAT, transferrin/TIBC, serum iron); CRP/ESR; renal & hepatic panels; B12/folate baseline (Weiss NEJM 2005 PMID 15758012; Weiss NEJM 2019 PMID 31532961)
   inputs: 718-7, 787-2, 2276-4, 2502-3, 1988-5
   actions: panel.cbc, panel.iron, panel.inflammation, panel.renal, panel.lft, workup.chronic_ida
   advance: CBC, iron studies, inflammatory markers, and renal/hepatic panels resulted
6. 6BRANCHING_WORKUP
   THE LOAD-BEARING DISCRIMINATION (ACD vs IDA vs ACD+IDA): when ferritin is equivocal (30–100 ng/mL with raised CRP), add soluble transferrin receptor and compute the sTfR/log-ferritin (Thomas) index — index <1 favours pure ACD, index >2 favours IDA or ACD+IDA (combined ferritin+sTfR+index lifts IDA detection from ~41% to ~92%; Skikne Am J Hematol 2011 PMID 21812017). Reticulocyte-Hb content (CHr/Ret-He) <28–29 pg flags functional iron deficiency unaffected by acute phase. Underlying-cause branches: occult-GI / MDS / myeloma workup in elderly or unexplained (workup.chronic_ida → source); AKI-on-CKD workup if renal function deteriorating (workup.aki_on_ckd); fever-of-unknown-origin / chronic-infection workup if febrile or TB/HIV/osteomyelitis suspected (workup.fuo). Always exclude B12/folate deficiency and haemolysis (Weiss NEJM 2019 PMID 31532961)
   inputs: 30248-9, 2132-9
   actions: workup.chronic_ida, workup.aki_on_ckd, workup.fuo, cascade.labs_command
   advance: ACD vs IDA vs ACD+IDA resolved and underlying-cause workup directed
7. 7DIFFERENTIAL
   Partition: pure anaemia of inflammation (high/normal ferritin, low TSAT, low retic, raised CRP, normocytic); ACD + concomitant absolute IDA (ferritin <100, high sTfR, high Thomas index, often microcytic); anaemia of CKD (relative EPO deficiency + hepcidin); anaemia of malignancy / chemotherapy; anaemia of chronic infection (TB/HIV/osteomyelitis); plus the always-exclude set — B12/folate deficiency, haemolysis, occult bleeding, MDS, myeloma, hypothyroidism, thalassaemia trait (Weiss NEJM 2019 PMID 31532961)
   advance: Terminal anaemia phenotype assigned with iron status and underlying cause
8. 8RISK_STRATIFICATION
   Severity by Hb and cardiopulmonary reserve; CKD stage (calc.ckd_epi_2021) drives ESA candidacy and Hb target band (~10–11.5 g/dL, individualised; KDIGO 2026). Screen depression/quality-of-life burden (calc.phq9) because fatigue and ESA/iron decisions hinge on symptom impact. Identify ESA-hyporesponsiveness (ongoing inflammation, functional iron deficiency, occult blood loss) (KDIGO 2026; ASCO/ASH 2019 PMID 30969847)
   inputs: 718-7, 20570-8
   actions: calc.ckd_epi_2021, calc.phq9
   advance: Severity tier, CKD-driven target, and ESA candidacy/hyporesponsiveness determined
9. 9TREATMENT
   TREAT THE UNDERLYING DISEASE FIRST (control inflammation — DMARDs/biologics for RA/SLE/IBD, antimicrobials for chronic infection, oncologic therapy, GDMT for HF; anaemia often resolves). Repletion of iron when absolute or functional ID (TSAT <20%; ferritin <100–200 ng/mL context-dependent) — IV iron preferred when inflammation impairs oral absorption / oral failed / CKD-HD / IBD active / HF (ferric carboxymaltose, ferric derisomaltose, ferumoxytol, iron sucrose; AFFIRM-AHF PMID 33197395). ESAs (epoetin/darbepoetin) per KDIGO 2026 for CKD anaemia not normalising on iron — target Hb ~10–11.5 g/dL, NOT normalisation (overshoot → stroke/VTE/HTN); per ASCO/ASH 2019 only for chemotherapy-induced anaemia with non-curative intent and Hb <10 (discuss thromboembolism + tumour-progression risk, shared decision — PMID 30969847). HIF-PHI daprodustat for CKD anaemia (ASCEND-ND non-inferior to darbepoetin on Hb and MACE — PMID 34739196; ASCEND-D dialysis — PMID 34739194) with cardiovascular/thrombosis caveats; roxadustat is non-US (no FDA approval) — narrative only. Restrictive transfusion threshold ~7 g/dL (8 g/dL with cardiac disease) — AABB 2023 PMID 37824153
   inputs: 718-7, 2502-3, 2276-4, 20570-8
   actions: cascade.labs_command
   advance: Underlying disease addressed and iron / ESA / HIF-PHI / transfusion plan executed
10. 10DISPOSITION
    Outpatient haematology / nephrology / oncology / rheumatology co-management for stable chronic anaemia; admit for symptomatic anaemia requiring transfusion, suspected acute bleed, or new anaemia requiring expedited malignancy/MDS workup; route by underlying disease engine (KDIGO 2026; AABB 2023 PMID 37824153)
    inputs: 718-7
    advance: Disposition set and specialty co-management arranged
11. 11MONITORING
    On IV iron: recheck TSAT + ferritin no sooner than 4 weeks post-dose (avoid spurious post-infusion ferritin rise) and Hb at 4–8 weeks. On ESA/HIF-PHI: Hb every 2–4 weeks during titration then monthly — hold/down-titrate if Hb >11.5 g/dL or rising >1 g/dL per 2 weeks; monitor BP and thrombotic events. Track inflammatory markers and underlying-disease activity; reassess for emergent IDA/bleeding if response is blunted (KDIGO 2026; ASCO/ASH 2019 PMID 30969847)
    inputs: 718-7, 2502-3, 2276-4
    actions: panel.cbc, panel.iron, cascade.labs_command
    advance: Monitoring cadence documented and Hb trajectory within target band
12. 12FOLLOWUP
    Interval review tied to underlying-disease control; periodic iron studies and CBC; re-evaluate ESA/HIF-PHI dose against the individualised Hb target; in elderly maintain a low threshold to re-investigate for occult malignancy/MDS if anaemia worsens or fails to track inflammation; patient education on adherence, transfusion-sparing goals, and red-flag symptoms (KDIGO 2026; Weiss NEJM 2019 PMID 31532961)
    inputs: 718-7, age
    actions: panel.cbc
    advance: Follow-up interval, education, and re-investigation triggers documented