Clinical Commander

Back to dossier
heme.anemia-of-chronic-disease.core.v1PRODUCTION
heme.anemia-of-chronic-disease.core.v1

Anaemia of Chronic Disease / Anaemia of Inflammation (incl. anaemia of CKD, malignancy, chronic infection, functional iron deficiency)

hematologychronicadultgeriatric
Hard-required inputs
0 / 8
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

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
2
Actions
0
Advance rule
Set
Advance when

Anaemia confirmed chronic and inflammatory context identified

Patient inputs (11)

Geriatric anaemia mandates exclusion of MDS / occult GI malignancy / myeloma even when an inflammatory cause is plausible (Weiss NEJM 2019 PMID 31532961)

eGFR / creatinine — CKD stage drives ESA & iron strategy and the Hb target band (KDIGO 2026 anaemia-in-CKD)

CKD / RA / SLE / IBD / chronic infection / malignancy / HF identifies the disease to treat first (Weiss NEJM 2019 PMID 31532961)

Haemoglobin defines anaemia severity and transfusion thresholds (AABB 2023 PMID 37824153)

MCV — ACD is normocytic; frank microcytosis raises probability of concomitant IDA or thalassaemia trait (Weiss NEJM 2005 PMID 15758012)

Ferritin — high/normal in pure ACD, low (<30 ng/mL) in IDA; acute-phase confounder pushes the ACD+IDA threshold up to <100 ng/mL (Weiss NEJM 2019 PMID 31532961)

Transferrin saturation (TSAT) — low in both ACD and IDA; <20% defines functional or absolute iron-restricted erythropoiesis (KDIGO 2026 anaemia-in-CKD)

CRP — anchors the inflammatory prior and reframes ferritin interpretation as an acute-phase reactant (Weiss NEJM 2019 PMID 31532961)

Soluble transferrin receptor — unaffected by inflammation; the sTfR/log-ferritin (Thomas) index is the load-bearing ACD-vs-IDA discriminator (Skikne Am J Hematol 2011 PMID 21812017)

B12 and folate — co-existing deficiency is a common reversible contributor in elderly/chronic-disease patients (Weiss NEJM 2019 PMID 31532961)

Potassium / electrolytes for CMP context when staging CKD and screening for tumour lysis / renal dysfunction

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationalseveresymptomatic_anemia_needs_transfusion
    Anaemia with angina / decompensated HF / syncope / Hb <7 g/dL (or <8 g/dL with cardiac disease) (AABB 2023 PMID 37824153)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereesa_hb_overshoot_or_vte_risk
    Hb >11.5 g/dL or rising >1 g/dL per 2 weeks on ESA/HIF-PHI, or new thrombotic event / uncontrolled HTN (KDIGO 2026)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenew_anemia_elderly_malignancy_mds
    New or worsening unexplained anaemia in an elderly patient, or pancytopenia / dysplastic indices / blasts (Weiss NEJM 2019 PMID 31532961)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesuspected_concomitant_ida_source_workup
    Ferritin <100 ng/mL with inflammation, high sTfR / high Thomas index, or microcytosis — suspected concomitant absolute IDA requiring bleeding-source workup (Skikne Am J Hematol 2011 PMID 21812017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateesa_hyporesponsiveness
    Inadequate Hb response despite adequate ESA dose and iron repletion (ongoing inflammation, occult blood loss, functional iron deficiency) (KDIGO 2026)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONrequiredDrives risk stratification
Loading…

Recommended regimen

Anaemia of chronic disease / inflammation management (IV iron + ESA + HIF-PHI + transfusion)
axis: acd_management
Selected axis "Anaemia of chronic disease / inflammation management (IV iron + ESA + HIF-PHI + transfusion)" by default fallback (first axis)
  • treat_underlying_inflammatory_disease
    first line
    disease_directed_therapy
    triggers: active_underlying_disease
    TREAT THE CAUSE FIRST — controlling inflammation (DMARD/biologic for RA/SLE/IBD, antimicrobials for chronic infection, oncologic therapy, GDMT for HF) lowers hepcidin and frequently corrects the anaemia (Weiss NEJM 2019 PMID 31532961)
  • ferric carboxymaltose
    first line
    IV iron
    750 mg (≥50 kg) or weight-based • IV • two doses ≥7 days apart (per total iron deficit) (max: max 1500 mg per course)
    triggers: TSAT_under_20, ferritin_under_100_to_200_context, oral_iron_failed_or_inflammation, IBD_active, HF_with_iron_deficiency
    IV iron preferred when inflammation impairs oral absorption; AFFIRM-AHF showed FCM reduced HF hospitalisations (RR 0.74, 95% CI 0.58–0.94) in iron-deficient HFrEF (Ponikowski Lancet 2020 PMID 33197395)
    rxcui 1433693
  • ferric derisomaltose
    first line
    IV iron
    20 mg/kg (single high-dose infusion typical) • IV • single dose (repeat per deficit)
    triggers: TSAT_under_20, high_single_dose_replacement_preferred, oral_iron_intolerant
    High single-dose IV iron repletion option; effective in inflammation-impaired absorption (KDIGO 2026 anaemia-in-CKD)
    rxcui 2274394
  • ferumoxytol
    second line
    IV iron
    510 mg • IV • two doses 3–8 days apart
    triggers: CKD_iron_deficiency, alternative_IV_iron_needed
    IV iron alternative, validated in CKD-associated functional/absolute iron deficiency (KDIGO 2026 anaemia-in-CKD)
    rxcui 473387
  • iron sucrose
    second line
    IV iron
    100–200 mg per session • IV • repeated sessions to total deficit
    triggers: CKD_hemodialysis, low_per_dose_protocol_preferred
    Established IV iron for haemodialysis-associated anaemia; per-session dosing fits HD schedule (KDIGO 2026; PIVOTAL strategy)
    rxcui 24909
  • ferrous sulfate
    second line
    oral iron
    325 mg (65 mg elemental) • PO • once daily or alternate-day
    triggers: mild_iron_deficiency_no_significant_inflammation, IV_access_unavailable
    Oral iron acceptable only when inflammation is mild (hepcidin-driven malabsorption blunts response in active inflammation); alternate-day dosing improves fractional absorption (Weiss NEJM 2019 PMID 31532961)
    rxcui 24947
  • epoetin alfa
    add on
    erythropoiesis-stimulating agent
    CKD: ~50 U/kg 1–3x/week or per protocol • SC • titrate to Hb target
    triggers: CKD_anemia_not_corrected_by_iron, chemo_induced_anemia_noncurative_Hb_under_10, iron_replete_persistent_symptomatic_anemia
    ESA for CKD anaemia not normalising on iron (KDIGO 2026, individualised Hb ~10–11.5 g/dL) or chemo-induced anaemia with non-curative intent and Hb <10 (ASCO/ASH 2019 PMID 30969847) — NOT curative, requires thromboembolism + tumour-progression shared decision
    rxcui 105694
  • darbepoetin alfa
    add on
    erythropoiesis-stimulating agent
    CKD: 0.45 mcg/kg weekly or 0.75 mcg/kg q2wk • SC • weekly to q2–4 weeks
    triggers: CKD_anemia_not_corrected_by_iron, less_frequent_dosing_preferred, chemo_induced_anemia_noncurative_Hb_under_10
    Long-acting ESA; comparator arm in ASCEND-ND (PMID 34739196); same Hb-ceiling and thrombosis caveats as epoetin (KDIGO 2026; ASCO/ASH 2019 PMID 30969847)
    rxcui 283838
  • methoxy polyethylene glycol-epoetin beta
    add on
    erythropoiesis-stimulating agent
    CKD: 0.6 mcg/kg q2wk or per protocol • SC • q2–4 weeks (monthly maintenance)
    triggers: CKD_anemia_maintenance, monthly_dosing_preferred
    Continuous erythropoietin receptor activator — monthly maintenance option for CKD anaemia (KDIGO 2026 anaemia-in-CKD)
    rxcui 729596
  • daprodustat
    second line
    HIF prolyl-hydroxylase inhibitor (HIF-PHI)
    oral, per CKD/dialysis-status protocol • PO • once daily
    triggers: CKD_anemia_oral_route_preferred, ESA_alternative_in_CKD, dialysis_or_non_dialysis_CKD
    Oral HIF-PHI; ASCEND-ND non-inferior to darbepoetin on Hb and MACE in non-dialysis CKD (PMID 34739196) and ASCEND-D in dialysis CKD (PMID 34739194); cardiovascular/thrombosis caveats apply, restricted to CKD anaemia
    rxcui 2628210
  • restrictive_red_cell_transfusion
    rescue
    blood product
    triggers: symptomatic_anemia, Hb_under_7, Hb_under_8_with_cardiac_disease, acute_bleeding
    Restrictive strategy — transfuse at Hb ~7 g/dL (8 g/dL with cardiac disease), single-unit then reassess; conditional lower-certainty in haematologic/oncologic adults (AABB 2023 PMID 37824153)

outpatient playbook — drug actions (4)

  1. 1. treat underlying disease
    disease-directed (DMARD/biologic/antimicrobial/oncologic/GDMT) • per disease • per disease protocol
    trigger: Active underlying inflammatory disease
    Lowers hepcidin; anaemia often resolves (Weiss NEJM 2019 PMID 31532961)
  2. 2. IV iron (ferric carboxymaltose)
    750 mg x2 (or weight-based) • IV • doses ≥7 days apart
    trigger: TSAT <20% and/or ferritin <100–200 with inflammation / oral failed
    IV preferred when inflammation impairs oral absorption (KDIGO 2026; AFFIRM-AHF PMID 33197395)
  3. 3. oral ferrous sulfate
    325 mg (65 mg elemental) • PO • daily or alternate-day
    trigger: Mild iron deficiency, minimal inflammation, IV unavailable
    Alternate-day improves fractional absorption; limited in active inflammation (Weiss NEJM 2019 PMID 31532961)
  4. 4. ESA (darbepoetin / epoetin) or HIF-PHI (daprodustat)
    per CKD protocol, titrate to Hb ~10–11.5 • SC (ESA) / PO (HIF-PHI) • weekly–monthly
    trigger: CKD anaemia not corrected by iron, or chemo-induced anaemia non-curative Hb <10
    KDIGO 2026; ASCO/ASH 2019 PMID 30969847; ASCEND-ND PMID 34739196 — individualised target, NOT normalisation

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Low haemoglobin — normocytic (sometimes mildly microcytic) anaemia (Weiss NEJM 2019 PMID 31532961); Anaemia in CKD on problem list (KDIGO 2026 anaemia-in-CKD); RA / SLE / IBD / chronic infection / malignancy / HF on problem list with anaemia (Weiss NEJM 2019 PMID 31532961).

Objective

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

Assessment

**Anaemia of Chronic Disease / Anaemia of Inflammation (incl. anaemia of CKD, malignancy, chronic infection, functional iron deficiency)** (heme.anemia-of-chronic-disease.core.v1).
Phenotype framing: 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)
Scope: 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)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Anaemia of chronic disease / inflammation management (IV iron + ESA + HIF-PHI + transfusion)**.
1. treat_underlying_inflammatory_disease (disease_directed_therapy, first line) — TREAT THE CAUSE FIRST — controlling inflammation (DMARD/biologic for RA/SLE/IBD, antimicrobials for chronic infection, oncologic therapy, GDMT for HF) lowers hepcidin and frequently corrects the anaemia (Weiss NEJM 2019 PMID 31532961)
2. ferric carboxymaltose 750 mg (≥50 kg) or weight-based IV two doses ≥7 days apart (per total iron deficit) (IV iron, first line) — IV iron preferred when inflammation impairs oral absorption; AFFIRM-AHF showed FCM reduced HF hospitalisations (RR 0.74, 95% CI 0.58–0.94) in iron-deficient HFrEF (Ponikowski Lancet 2020 PMID 33197395)
3. ferric derisomaltose 20 mg/kg (single high-dose infusion typical) IV single dose (repeat per deficit) (IV iron, first line) — High single-dose IV iron repletion option; effective in inflammation-impaired absorption (KDIGO 2026 anaemia-in-CKD)
4. ferumoxytol 510 mg IV two doses 3–8 days apart (IV iron, second line) — IV iron alternative, validated in CKD-associated functional/absolute iron deficiency (KDIGO 2026 anaemia-in-CKD)
5. iron sucrose 100–200 mg per session IV repeated sessions to total deficit (IV iron, second line) — Established IV iron for haemodialysis-associated anaemia; per-session dosing fits HD schedule (KDIGO 2026; PIVOTAL strategy)
6. ferrous sulfate 325 mg (65 mg elemental) PO once daily or alternate-day (oral iron, second line) — Oral iron acceptable only when inflammation is mild (hepcidin-driven malabsorption blunts response in active inflammation); alternate-day dosing improves fractional absorption (Weiss NEJM 2019 PMID 31532961)
7. epoetin alfa CKD: ~50 U/kg 1–3x/week or per protocol SC titrate to Hb target (erythropoiesis-stimulating agent, add on) — ESA for CKD anaemia not normalising on iron (KDIGO 2026, individualised Hb ~10–11.5 g/dL) or chemo-induced anaemia with non-curative intent and Hb <10 (ASCO/ASH 2019 PMID 30969847) — NOT curative, requires thromboembolism + tumour-progression shared decision
8. darbepoetin alfa CKD: 0.45 mcg/kg weekly or 0.75 mcg/kg q2wk SC weekly to q2–4 weeks (erythropoiesis-stimulating agent, add on) — Long-acting ESA; comparator arm in ASCEND-ND (PMID 34739196); same Hb-ceiling and thrombosis caveats as epoetin (KDIGO 2026; ASCO/ASH 2019 PMID 30969847)
9. methoxy polyethylene glycol-epoetin beta CKD: 0.6 mcg/kg q2wk or per protocol SC q2–4 weeks (monthly maintenance) (erythropoiesis-stimulating agent, add on) — Continuous erythropoietin receptor activator — monthly maintenance option for CKD anaemia (KDIGO 2026 anaemia-in-CKD)
10. daprodustat oral, per CKD/dialysis-status protocol PO once daily (HIF prolyl-hydroxylase inhibitor (HIF-PHI), second line) — Oral HIF-PHI; ASCEND-ND non-inferior to darbepoetin on Hb and MACE in non-dialysis CKD (PMID 34739196) and ASCEND-D in dialysis CKD (PMID 34739194); cardiovascular/thrombosis caveats apply, restricted to CKD anaemia
11. restrictive_red_cell_transfusion (blood product, rescue) — Restrictive strategy — transfuse at Hb ~7 g/dL (8 g/dL with cardiac disease), single-unit then reassess; conditional lower-certainty in haematologic/oncologic adults (AABB 2023 PMID 37824153)

Setting playbook (outpatient) — Primary-care / specialty co-management: confirm inflammatory mechanism, resolve ACD-vs-IDA, treat the underlying disease, replete iron and titrate ESA/HIF-PHI to an individualised Hb target while sparing transfusion (KDIGO 2026; Weiss NEJM 2019 PMID 31532961)
12. treat underlying disease disease-directed (DMARD/biologic/antimicrobial/oncologic/GDMT) per disease per disease protocol — Active underlying inflammatory disease (Lowers hepcidin; anaemia often resolves (Weiss NEJM 2019 PMID 31532961))
13. IV iron (ferric carboxymaltose) 750 mg x2 (or weight-based) IV doses ≥7 days apart — TSAT <20% and/or ferritin <100–200 with inflammation / oral failed (IV preferred when inflammation impairs oral absorption (KDIGO 2026; AFFIRM-AHF PMID 33197395))
14. oral ferrous sulfate 325 mg (65 mg elemental) PO daily or alternate-day — Mild iron deficiency, minimal inflammation, IV unavailable (Alternate-day improves fractional absorption; limited in active inflammation (Weiss NEJM 2019 PMID 31532961))
15. ESA (darbepoetin / epoetin) or HIF-PHI (daprodustat) per CKD protocol, titrate to Hb ~10–11.5 SC (ESA) / PO (HIF-PHI) weekly–monthly — CKD anaemia not corrected by iron, or chemo-induced anaemia non-curative Hb <10 (KDIGO 2026; ASCO/ASH 2019 PMID 30969847; ASCEND-ND PMID 34739196 — individualised target, NOT normalisation)

Non-pharmacologic actions:
- Shared decision-making on ESA risk (VTE, tumour progression) before starting in cancer (ASCO/ASH 2019 PMID 30969847)
- Co-manage with nephrology / oncology / rheumatology / GI by underlying disease
- Patient education: adherence, transfusion-sparing goals, fatigue tracking, red-flag symptoms

AVOID / contraindication checks:
- ESA Hb ceiling — do NOT target normalisation; hold/down titrate if Hb >11.5 g/dL or rising >1 g/dL per 2 weeks (KDIGO 2026; overshoot → stroke/VTE/HTN)
- ESA contraindicated in uncontrolled hypertension (KDIGO 2026)
- ESA active malignancy nuance — only chemo induced anaemia, non curative intent, Hb <10, shared decision re tumour progression + thromboembolism; avoid when curative intent therapy (ASCO/ASH 2019 PMID 30969847)
- ESA history of thrombosis/stroke — individualise, lowest effective dose (KDIGO 2026)
- HIF PHI daprodustat — cardiovascular/thrombosis surveillance; restrict to CKD anaemia indication (ASCEND ND PMID 34739196)
- IV iron — ensure absolute/functional iron deficiency before dosing; recheck ferritin/TSAT ≥4 weeks post infusion to avoid spurious overshoot (KDIGO 2026)
- Do not give iron/ESA without addressing occult bleeding or malignancy in unexplained/elderly anaemia (Weiss NEJM 2019 PMID 31532961)
- Roxadustat excluded — no FDA approval / no resolvable RxNorm CUI; not a US treatment option (narrative only)

Monitoring

Regimen monitoring:
- Hb q2-4w during ESA or HIFPHI titration then q1m
- TSAT and ferritin no sooner than 4w post IV iron
- BP each visit on ESA or HIFPHI
- CRP and underlying disease activity each review
- reassess for IDA or bleeding if response blunted

Setting (outpatient) monitoring:
- Hb q2–4w during titration then monthly (KDIGO 2026)
- TSAT + ferritin ≥4w after IV iron (KDIGO 2026)
- BP each visit on ESA/HIF-PHI (KDIGO 2026)
- Underlying-disease activity + CRP each review (Weiss NEJM 2019 PMID 31532961)

Follow-up plan: 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)
- Close-out criterion: Follow-up interval, education, and re-investigation triggers documented

Monitoring phase: 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)

Disposition

Current setting: outpatient — Primary-care / specialty co-management: confirm inflammatory mechanism, resolve ACD-vs-IDA, treat the underlying disease, replete iron and titrate ESA/HIF-PHI to an individualised Hb target while sparing transfusion (KDIGO 2026; Weiss NEJM 2019 PMID 31532961)

Disposition criteria:
- Continue chronic outpatient management if Hb in target band and underlying disease controlled
- Refer to disease-specific engine for primary management (CKD/cancer/IBD/SLE)
- Admit if symptomatic anaemia, suspected acute bleed, or expedited malignancy workup needed

Escalation triggers (move to higher acuity):
- Symptomatic anaemia (angina / dyspnoea at rest / syncope) → inpatient transfusion assessment (AABB 2023 PMID 37824153)
- Unexplained or worsening anaemia in elderly → expedite GI / MDS / myeloma workup (Weiss NEJM 2019 PMID 31532961)
- Hb overshoot >11.5 g/dL or rising >1 g/dL per 2 weeks on ESA/HIF-PHI → hold/down-titrate (KDIGO 2026)
- New thrombotic event on ESA → reassess indication (KDIGO 2026)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] Anaemia with angina / decompensated HF / syncope / Hb <7 g/dL (or <8 g/dL with cardiac disease) (AABB 2023 PMID 37824153)
- [SEVERE] Hb >11.5 g/dL or rising >1 g/dL per 2 weeks on ESA/HIF-PHI, or new thrombotic event / uncontrolled HTN (KDIGO 2026)
- [SEVERE] New or worsening unexplained anaemia in an elderly patient, or pancytopenia / dysplastic indices / blasts (Weiss NEJM 2019 PMID 31532961)

Citations

- KDIGO 2026 Anaemia in CKD + ASCO/ASH 2019 ESA in Cancer-Associated Anaemia + Weiss/Ganz/Goodnough NEJM 2019 Anaemia of Inflammation + AABB 2023 RBC Transfusion [PMID:15758012](https://pubmed.ncbi.nlm.nih.gov/15758012/)
- Cited evidence (PMID 31532961) [PMID:31532961](https://pubmed.ncbi.nlm.nih.gov/31532961/)
- Cited evidence (PMID 30401705) [PMID:30401705](https://pubmed.ncbi.nlm.nih.gov/30401705/)
- Cited evidence (PMID 21812017) [PMID:21812017](https://pubmed.ncbi.nlm.nih.gov/21812017/)
- Cited evidence (PMID 34739196) [PMID:34739196](https://pubmed.ncbi.nlm.nih.gov/34739196/)

Last reconciled with current guidelines: 2026-05-16.
References
  • KDIGO 2026 Anaemia in CKD + ASCO/ASH 2019 ESA in Cancer-Associated Anaemia + Weiss/Ganz/Goodnough NEJM 2019 Anaemia of Inflammation + AABB 2023 RBC Transfusion — PMID:15758012
  • Cited evidence (PMID 31532961) — PMID:31532961
  • Cited evidence (PMID 30401705) — PMID:30401705
  • Cited evidence (PMID 21812017) — PMID:21812017
  • Cited evidence (PMID 34739196) — PMID:34739196