遺傳性紅血球膜缺陷

Buzzwords → Dx

Diagnostic Criteria

• CBC + smear: spherocytes (HS), elliptocytes (HE), stomatocytes; ↑MCHC + ↑RDW.
• DAT negative (excludes AIHA).
• EMA flow cytometry (eosin-5-maleimide binding to band 3) — sensitive and specific for HS.
• Osmotic fragility test (older) — RBCs lyse at higher saline tonicity in HS.
• Family history — AD in 75 % of HS.
• Genetic testing for atypical or compound forms.

Workup

• CBC + smear + reticulocyte count.
• DAT (rule out AIHA).
• LDH, haptoglobin, indirect bilirubin (hemolysis labs).
• Iron + ferritin (chronic hemolysis can deplete folate; iron usually adequate or elevated).
• Folate level.
• EMA flow cytometry + osmotic fragility.
• Abdominal US (splenomegaly + gallstones).
• Genetic testing if atypical.

Treatment Algorithm

flowchart TD
  A[Confirmed HS] --> B[Folate supplementation 1 mg/d<br>chronic hemolysis]
  B --> C{Severity}
  C -- mild (Hb >11) --> D[Observation; folate]
  C -- moderate (Hb 8-11) --> E[Splenectomy considered<br>esp. with gallstones / cholecystitis]
  C -- severe / transfusion-dependent --> F[Splenectomy after age 5-6<br>OR partial splenectomy in young]
  E --> G[Vaccinations 2 wk pre-op<br>PCV20 + PPSV23 + MenACWY + MenB + Hib]
  F --> G
  G --> H[Lifelong infection precautions<br>penicillin ppx in children<br>aggressive febrile workup]
  G --> I[Cholecystectomy if symptomatic gallstones<br>often combined with splenectomy]
  D --> J{Aplastic crisis (parvovirus B19)?}
  E --> J
  F --> J
  J -- yes --> K[Supportive transfusion × 2-4 wk<br>self-limited]

Pearls / Pitfalls

• Spherocytes + DAT negative = HS, NOT AIHA. Classic board distinction.
• MCHC elevated is highly specific for HS (cell shape causing volume mismatch in counter).
• Osmotic fragility false negative with concomitant iron deficiency or jaundice; EMA flow more reliable.
• Splenectomy reduces hemolysis (RBCs survive longer outside spleen) — Hb normalizes, no longer transfuse-dependent. Spherocytes remain on smear (bone marrow continues to make them).
• Splenectomy timing: delay to age 5–6 (immune system maturity). Partial splenectomy preserves immune function in young children.
• Splenectomy increases lifelong infection risk (encapsulated organisms — pneumococcus, H. influenzae, meningococcus). Vaccinate 2 wk pre-op (PCV20 + PPSV23 + MenACWY + MenB + Hib + influenza). Penicillin V prophylaxis in children. Lifelong fever workup.
• Aplastic crisis with parvovirus B19 is dramatic — sudden Hb drop, low retic count → supportive care + transfusions; self-limited 2–4 wk.
• Pigment gallstones are common; combine cholecystectomy with splenectomy when feasible.
• Hereditary xerocytosis (DHS, PIEZO1): splenectomy CONTRAINDICATED — worsens thrombosis (pulmonary HTN, splanchnic thrombosis). Distinguish from HS!
• Hereditary elliptocytosis (HE) — mild hemolysis; usually no treatment. HPP variant in newborns is severe (severe poikilocytes, neonatal jaundice).
• Southeast Asian ovalocytosis (SAO) — band 3 deletion; usually asymptomatic; malaria-resistant.
• Folate supplementation is critical in chronic hemolysis to prevent megaloblastic crisis.

Cross-references

• AIHA — DAT-positive spherocyte differential
• G6PD — oxidative hemolysis differential
• Post-splenectomy infection prophylaxis
• Hemolysis Workup algorithm

相關題目

• Q-118 — HS — distinguishing from warm AIHA
• Q-119 — Hereditary xerocytosis (DHS) — splenectomy contraindication
• Q-120 — HS — parvovirus B19 aplastic crisis

Sources