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heme.sickle-cell.core.v1PRODUCTION
heme.sickle-cell.core.v1

Sickle Cell Disease (chronic management + acute crisis)

hematologychronicacuteadultpediatric
Hard-required inputs
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Care setting:

Encounter flow

12/12 authored

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

Current phase

Frame

Detailed

Determine presentation type — VOC / ACS / sequestration / aplastic / stroke / priapism / chronic visit (ASH 2020)

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Presentation type assigned

Patient inputs (9)

Pediatric vs adult management; functional asplenia by age 5; gene therapy candidacy (NHLBI 2014; ASH 2020)

HbSS / HbSC / HbS-beta-zero / HbS-beta-plus — severity differs (ASH 2020)

ACS triage; hypoxia drives transfusion threshold (ASH 2020)

Fever = empirical broad-spectrum abx; functional asplenia (ASH 2020; NHLBI 2014)

Hb baseline + retic + WBC for sepsis; aplastic crisis (low retic) (NHLBI 2014)

Chronic transfusion vs gene therapy planning (Adams NEJM 1998 STOP)

Chelation thresholds (ferritin >1000 + LIC) (NHLBI 2014)

Aplastic crisis (parvo B19) vs splenic sequestration vs hemolytic crisis (NHLBI 2014)

ACS criteria (new infiltrate) (ASH 2020)

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

Severity triggers (7)

7 need judgement
  • informationallife_threateningacute_chest_syndrome
    Fever + cough/dyspnea/hypoxia + new pulmonary infiltrate (ASH 2020)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningstroke_in_scd
    Acute neurologic deficit in SCD patient (ASH 2020)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningmulti_organ_failure
    Acute organ dysfunction in 2+ systems during VOC (ASH 2020)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverefever_in_scd
    Temperature ≥38.5°C in SCD patient (ASH 2020; NHLBI 2014)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepriapism_over_4h
    Sustained priapism >4 hours (ASH 2020)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresplenic_sequestration
    Acute Hb drop >2 below baseline + splenomegaly + pancytopenia/cytopenia (NHLBI 2014)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereaplastic_crisis
    Hb drop with absolute reticulocyte count <1% (NHLBI 2014)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

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Recommended regimen

Disease-modifying therapy (chronic)
axis: scd_disease_modifying
Selected axis "Disease-modifying therapy (chronic)" by default fallback (first axis)
  • hydroxyurea
    first line
    antimetabolite
    triggers: HbSS_or_HbS_b0, recurrent_voc_or_acs_or_severe_anemia
    MSH NEJM 1995; BABY HUG; ASH 2020; foundation of DMT
    rxcui 5552
  • l_glutamine
    add on
    amino_acid
    triggers: recurrent_voc_on_hydroxyurea
    BEACON NEJM 2018
    rxcui 4885
  • crizanlizumab
    add on
    p_selectin_inhibitor
    triggers: us_only, verify_local_availability
    SUSTAIN NEJM 2017 — STAND phase 3 FAILED; EU/UK revoked 2023–2024; clinical benefit questioned
    rxcui 2262279
  • exa_cel_casgevy
    rescue
    gene_therapy_crispr
    triggers: transfusion_dependent_or_severe_voc, gene_therapy_eligible
    FDA approval Dec 2023; one-time CRISPR-edited autologous HSC
    rxcui 2671667
  • lovo_cel_lyfgenia
    rescue
    gene_therapy_lentiviral
    triggers: transfusion_dependent_or_severe_voc, gene_therapy_eligible
    FDA approval Dec 2023; lentiviral β-globin
    rxcui 2671958

outpatient playbook — drug actions (6)

  1. 1. hydroxyurea
    15-20 mg/kg PO daily, titrate to 35 mg/kg or MTD • PO • daily
    trigger: HbSS or HbS-β° (consider in HbSC with severe disease)
    MSH NEJM 1995; ASH 2020 foundation
  2. 2. L-glutamine
    0.3 g/kg PO BID • PO • BID
    trigger: Recurrent VOC despite hydroxyurea
    BEACON NEJM 2018
  3. 3. penicillin V (peds)
    125 mg PO BID until age 5 • PO • BID
    trigger: Pediatric SCD (HbSS/HbSβ°)
    Functional asplenia prophylaxis (NHLBI 2014)
  4. 4. gene therapy referral
    Casgevy or Lyfgenia per protocol • IV cellular • one-time
    trigger: Severe disease + transplant-eligible
    FDA approval Dec 2023 (ASH 2020)
  5. 5. chronic transfusion
    Simple or exchange to HbS <30% • IV • q3-6 weeks
    trigger: Stroke prevention (TCD positive) or refractory crises
    STOP NEJM 1998
  6. 6. iron chelation
    Deferasirox 14-28 mg/kg PO daily • PO • daily
    trigger: Ferritin >1000 + LIC elevated
    Iron overload prevention (NHLBI 2014; ASH 2020)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Vaso-occlusive pain crisis (ASH 2020; NHLBI 2014); Fever in SCD (functional asplenia — sepsis until proven otherwise) (ASH 2020); Chest pain / dyspnea / hypoxia → ACS workup (ASH 2020).

Objective

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

Assessment

**Sickle Cell Disease (chronic management + acute crisis)** (heme.sickle-cell.core.v1).
Phenotype framing: Crisis types (VOC / ACS / sequestration / aplastic / hemolytic / stroke / priapism / nephropathy / pulm HTN / AVN) (ASH 2020)
Scope: Determine presentation type — VOC / ACS / sequestration / aplastic / stroke / priapism / chronic visit (ASH 2020)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Disease-modifying therapy (chronic)**.
1. hydroxyurea (antimetabolite, first line) — MSH NEJM 1995; BABY HUG; ASH 2020; foundation of DMT
2. l_glutamine (amino_acid, add on) — BEACON NEJM 2018
3. crizanlizumab (p_selectin_inhibitor, add on) — SUSTAIN NEJM 2017 — STAND phase 3 FAILED; EU/UK revoked 2023–2024; clinical benefit questioned
4. exa_cel_casgevy (gene_therapy_crispr, rescue) — FDA approval Dec 2023; one-time CRISPR-edited autologous HSC
5. lovo_cel_lyfgenia (gene_therapy_lentiviral, rescue) — FDA approval Dec 2023; lentiviral β-globin

Setting playbook (outpatient) — Disease modification, infection prevention, complication surveillance, transition to gene therapy if eligible (ASH 2020; NASCC 2024)
6. hydroxyurea 15-20 mg/kg PO daily, titrate to 35 mg/kg or MTD PO daily — HbSS or HbS-β° (consider in HbSC with severe disease) (MSH NEJM 1995; ASH 2020 foundation)
7. L-glutamine 0.3 g/kg PO BID PO BID — Recurrent VOC despite hydroxyurea (BEACON NEJM 2018)
8. penicillin V (peds) 125 mg PO BID until age 5 PO BID — Pediatric SCD (HbSS/HbSβ°) (Functional asplenia prophylaxis (NHLBI 2014))
9. gene therapy referral Casgevy or Lyfgenia per protocol IV cellular one-time — Severe disease + transplant-eligible (FDA approval Dec 2023 (ASH 2020))
10. chronic transfusion Simple or exchange to HbS <30% IV q3-6 weeks — Stroke prevention (TCD positive) or refractory crises (STOP NEJM 1998)
11. iron chelation Deferasirox 14-28 mg/kg PO daily PO daily — Ferritin >1000 + LIC elevated (Iron overload prevention (NHLBI 2014; ASH 2020))

Non-pharmacologic actions:
- Annual TCD (peds) (Adams NEJM 1998 STOP)
- Annual ophthalmologic exam (NASCC 2024)
- Annual echo for pulmonary HTN (NASCC 2024)
- Genetic counseling (NASCC 2024)
- Pregnancy planning (ASH 2020)
- Education on hydration, avoiding cold/hypoxia/altitude (NHLBI 2014)

AVOID / contraindication checks:
- Hydroxyurea monitor CBC q4w then q8w (ASH 2020)
- Crizanlizumab availability check (Ataga NEJM 2017 SUSTAIN)
- Gene therapy fertility counselling (ASH 2020)

Monitoring

Regimen monitoring:
- CBC q2-4w during HU titration then q8-12w (ASH 2020)
- HbF q3m to assess HU response (ASH 2020)

Setting (outpatient) monitoring:
- CBC + retic q1-3m on hydroxyurea (ASH 2020)
- HbS% q3m on chronic transfusion (ASH 2020)
- Ferritin q3m if chronic transfusion (NHLBI 2014)
- Urinalysis annually (NASCC 2024)

Follow-up plan: Health maintenance per NASCC 2024: vaccinations (penicillin prophylaxis ages <5), TCD, retinopathy screen, baseline echo, contraception/pregnancy planning, cognitive assessment, transition to adult care
- Close-out criterion: Maintenance plan documented

Monitoring phase: Daily Hb + retic during admission; HbS% on chronic transfusion; TCD annually peds (Adams NEJM 1998 STOP); ferritin q3m on chronic transfusion; eGFR for SCD nephropathy (ASH 2020; NHLBI 2014)

Disposition

Current setting: outpatient — Disease modification, infection prevention, complication surveillance, transition to gene therapy if eligible (ASH 2020; NASCC 2024)

Disposition criteria:
- Continue current regimen if stable (ASH 2020)
- Refer to gene therapy if severe + eligible (ASH 2020)
- Refer to chronic transfusion if stroke risk (Adams NEJM 1998 STOP)

Escalation triggers (move to higher acuity):
- New stroke symptoms → ED + exchange (ASH 2020)
- Severe pain crisis not controlled at home → ED (NHLBI 2014)
- Fever → ED (sepsis prophylaxis) (ASH 2020; NHLBI 2014)
- Acute drop in Hb >2 below baseline → workup splenic sequestration / aplastic (NHLBI 2014)

Patient Action Plan

**SCD Crisis Action Plan + Home Management**
Personalised values: baseline_hemoglobin, home_pain_regimen, genotype, last_crisis_date, gene_therapy_eligibility.

**Stable — feeling well** (green):
Triggers:
- No pain or pain at baseline (ASH 2020)
- No fever (ASH 2020)
- Eating and drinking well (NHLBI 2014)
- Taking hydroxyurea/L-glutamine as prescribed (ASH 2020)
Actions:
- Continue hydroxyurea/L-glutamine as prescribed (ASH 2020)
- Stay well hydrated (3-4 L/day for adults) (NHLBI 2014)
- Avoid extreme cold, high altitude, dehydration (NHLBI 2014)
- Continue penicillin (peds) and all vaccinations (NHLBI 2014; NASCC 2024)
- Keep all clinic appointments (NASCC 2024)

**Caution — early crisis warning** (yellow):
Triggers:
- Mild pain in usual sites (legs, back, chest, abdomen) (NHLBI 2014)
- Fatigue more than usual (NHLBI 2014)
- Decreased appetite (NHLBI 2014)
- Slight fever (<38.5 C) (ASH 2020)
- Mild URI symptoms (ASH 2020)
Actions:
- Increase fluids (NHLBI 2014)
- Take home pain regimen as prescribed (NSAIDs cautiously, opioids per home plan) (NHLBI 2014)
- Continue all baseline medications (ASH 2020)
- Use heat packs to affected areas (NHLBI 2014)
- Call SCD clinic within 4-8 hours (ASH 2020)
- If home regimen ineffective in 4 hours → ED (ASH 2020)
Contact provider when:
- Pain not controlled with home regimen (NHLBI 2014)
- Persistent fever (ASH 2020)
- Cough or shortness of breath (ASH 2020)
- Decreased urine output (NHLBI 2014)

**Medical alert — go to ED now** (red):
Triggers:
- Severe pain not controlled by home regimen (ASH 2020)
- Fever ≥38.5 C (ASH 2020; NHLBI 2014)
- Chest pain or trouble breathing (ASH 2020)
- Acute neurologic symptoms (weakness, slurred speech, confusion, vision changes) (ASH 2020)
- Priapism (sustained erection >2 hours) (ASH 2020)
- Severe abdominal pain or sudden splenic enlargement (NHLBI 2014)
- Sudden worsening of anemia (severe pallor, dizziness) (NHLBI 2014)
Actions:
- Go to ED immediately (ASH 2020)
- Transfer criteria — request transfer to SCD-specialized center if local ED limited (ASH 2020)
- Bring home medication list and last clinic notes (ASH 2020)
- Tell ED you have SCD genotype (HbSS/HbSC/HbS-beta-zero/HbS-beta-plus) (ASH 2020)
- Request hematology consult (ASH 2020)
Contact provider when:
- Any red zone symptom — go to ED immediately (ASH 2020)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Fever + cough/dyspnea/hypoxia + new pulmonary infiltrate (ASH 2020)
- [LIFE_THREATENING] Acute neurologic deficit in SCD patient (ASH 2020)
- [LIFE_THREATENING] Acute organ dysfunction in 2+ systems during VOC (ASH 2020)

Citations

- ASH 2020 SCD Guidelines (multiple Blood Advances) + NHLBI 2014 + NASCC 2024 Health Maintenance + ASH 2025 draft hydroxyurea [PMID:7715639](https://pubmed.ncbi.nlm.nih.gov/7715639/)
- Cited evidence (PMID 9647873) [PMID:9647873](https://pubmed.ncbi.nlm.nih.gov/9647873/)
- Cited evidence (PMID 30021096) [PMID:30021096](https://pubmed.ncbi.nlm.nih.gov/30021096/)
- Cited evidence (PMID 38661449) [PMID:38661449](https://pubmed.ncbi.nlm.nih.gov/38661449/)
- Cited evidence (PMID 27959701) [PMID:27959701](https://pubmed.ncbi.nlm.nih.gov/27959701/)

Last reconciled with current guidelines: 2026-05-22.
References
  • ASH 2020 SCD Guidelines (multiple Blood Advances) + NHLBI 2014 + NASCC 2024 Health Maintenance + ASH 2025 draft hydroxyurea — PMID:7715639
  • Cited evidence (PMID 9647873) — PMID:9647873
  • Cited evidence (PMID 30021096) — PMID:30021096
  • Cited evidence (PMID 38661449) — PMID:38661449
  • Cited evidence (PMID 27959701) — PMID:27959701