鐮刀型紅血球病

Buzzwords → Dx

Diagnostic Criteria

• Newborn screening (US): mandatory (HPLC). HbSS, HbSC, HbS-β-thal vs HbAS (trait).
• Adult diagnosis (immigrant or unscreened): Hb electrophoresis or HPLC.
• Genetic counseling for HbAS partners — fetal SCD risk.

Workup

• CBC + retic (chronic hemolysis baseline).
• Hb electrophoresis or HPLC.
• Iron studies, B12, folate (chronic hemolysis can deplete folate).
• TCD in children 2–16 yo annually (stroke screening).
• Echo with TRJV (PHTN).
• Renal: UA, microalbumin, eGFR.
• Vaccinations: PCV20 + PPSV23 + MenACWY + MenB + Hib + influenza + RZV (functional asplenia).
• Eye exam annually (proliferative retinopathy esp. HbSC).
• Iron overload monitoring (ferritin, MRI T2*) if chronic transfusions.

Treatment Algorithm

flowchart TD
  A[Confirmed SCD] --> B[Disease-modifying baseline:<br>hydroxyurea start age 9 mo<br>+ folate + penicillin until age 5]
  B --> C{Acute presentation?}
  C -- VOC pain crisis --> D[IV fluids + opioids + warmth<br>incentive spirometry<br>r/o ACS]
  C -- ACS new infiltrate + fever/hypoxia --> E[O₂ + abx + IVF + analgesia<br>exchange transfusion if severe<br>NIV / intubation as needed]
  C -- splenic sequestration --> F[Transfuse + splenectomy if recurrent<br>vaccinate first]
  C -- aplastic crisis (parvovirus B19) --> G[Supportive RBC transfusion<br>self-limited 2-4 wk]
  C -- stroke / TCD high --> H[Exchange transfusion target HbS <30%<br>chronic ppx until age 16-18 (STOP)<br>or hydroxyurea TWITCH]
  C -- priapism >4 h --> I[Exchange transfusion + urology]
  B --> J{Disease-modifying escalation}
  J -- still painful/anemic on HU --> K[+ L-glutamine OR crizanlizumab<br>+ voxelotor for symptomatic anemia]
  J -- frequent ACS / strokes / PHTN<br>or transfusional iron overload --> L[Curative options:<br>allo-HCT (sibling match)<br>OR gene therapy (exa-cel Casgevy / lovo-cel Lyfgenia)]

Pearls / Pitfalls

• Hydroxyurea is foundational — start age 9 mo for HbSS regardless of severity. Increases HbF, reduces sickling, VOC, ACS, mortality. Mandatory contraception (teratogenic). Watch CBC for myelosuppression.
• ACS is the leading cause of adult mortality. Triggers: VOC, infection, post-op atelectasis. Exchange transfusion (vs simple) for severe ACS; aim HbS <30 %.
• Hb in SCD is not the right number to chase. Avoid over-transfusion (target Hb 9–10 g/dL during exchange; >10 worsens viscosity).
• Penicillin V prophylaxis until age 5 (functional asplenia → encapsulated organisms — pneumococcus, H. influenzae, meningococcus). Vaccinate aggressively (PCV20, PPSV23, MenACWY, MenB, Hib).
• Sickle trait (HbAS): generally asymptomatic. Splenic infarction at altitude, exertional rhabdomyolysis, renal medullary carcinoma association (rare). Renal: hyposthenuria, hematuria.
• HbSC disease: milder than HbSS but higher rate of proliferative retinopathy + avascular necrosis. Eye exam mandatory.
• HbS-β-thal: S-β⁰ (severe, like HbSS) vs S-β⁺ (milder).
• Voxelotor binds HbS → keeps R-state → reduces polymerization. Increases Hb but interferes with HbS quantitation; monitor by Hb only, not HbS%.
• Crizanlizumab (anti-P-selectin) reduces VOC frequency (SUSTAIN trial); SC monthly.
• Gene therapy approvals: Casgevy (exa-cel, CRISPR BCL11A → ↑HbF) and Lyfgenia (lovo-cel, lentiviral βT87Q) — FDA-approved 2023 for severe SCD ≥12 yo. One-time after myeloablation; high cost; emerging long-term safety.
• Allo-HCT (matched sibling) has been curative for decades; still gold standard if available + young + minimal organ damage.
• Iron chelation for transfusion-dependent SCD: deferasirox preferred (also reduces some SCD-specific complications).
• Pregnancy in SCD: high-risk; transfusion threshold debated; hydroxyurea held during pregnancy.
• Avoid hypoxia, dehydration, cold, altitude — common VOC triggers.
• Surgical preparation: simple transfusion to Hb 10 g/dL (TAPS trial).

Cross-references

• SCD Crises — ACS, VOC, splenic sequestration, priapism
• Allo-HCT for SCD
• Gene therapy — Casgevy, Lyfgenia
• Iron chelation for chronic transfusions
• Penicillin + vaccinations
• Hemoglobinopathy DDx

相關題目

• Q-124 — SCD — acute chest syndrome management
• Q-125 — SCD — hydroxyurea indication in pediatric
• Q-126 — SCD — gene therapy options
• Q-170 — SCD — RBC exchange (erythrocytapheresis)
• Q-174 — SCD — antigen-matched RBC transfusion
• Q-193 — SCD vaso-occlusive pain crisis — pain management

Sources