陣發性夜間血紅素尿症

Buzzwords → Dx

Diagnostic Criteria

• Flow cytometry on PB: CD55 + CD59 deficiency on RBCs (PNH II partial, PNH III complete) + FLAER negative on granulocytes/monocytes (most sensitive).
• Clone size: ≥1 % (clinically relevant); large clones ≥50 % typically symptomatic.
• Categories:
  • Classic PNH: intravascular hemolysis predominant.
  • PNH/AA overlap: marrow failure + clone.
  • Subclinical PNH: small clone, no hemolysis or marrow failure.

Workup

• CBC + smear + retic (chronic hemolysis with iron deficiency picture).
• LDH, haptoglobin (low), indirect bili (high).
• Urinalysis with hemosiderin (Prussian blue stain; chronic hemoglobinuria).
• Iron studies (often deficient from urine loss).
• DAT (negative).
• PNH flow cytometry with FLAER + CD55 + CD59 — RBCs + granulocytes + monocytes.
• Marrow biopsy to assess for AA or MDS.
• Doppler abdominal vessels + brain MRI/V if thrombosis suspected.
• Folate supplementation.
• Pre-eculizumab vaccinations: meningococcal ACWY + B + PCV20 + PPSV23 + Hib + influenza.

Treatment Algorithm

flowchart TD
  A[Confirmed PNH<br>flow cytometry] --> B{Clinical phenotype}
  B -- subclinical small clone, no hemolysis/thrombosis --> C[Observation<br>q3-12 mo flow + CBC]
  B -- AA overlap dominant --> D[Treat as aplastic anemia<br>+ eculizumab if hemolysis]
  B -- classic hemolytic PNH --> E[Anti-C5: eculizumab or ravulizumab<br>+ MENINGOCOCCAL VACCINATION + ABX PROPHYLAXIS]
  E --> F{Breakthrough hemolysis or extravascular hemolysis on anti-C5?}
  F -- yes --> G[Add proximal complement inhibitor:<br>pegcetacoplan anti-C3<br>or iptacopan anti-factor B (PO)<br>or danicopan anti-factor D (PO adjunct)]
  E --> H{Thrombosis?}
  H -- yes --> I[Anticoagulation indefinite<br>+ continue complement inhibitor]
  C --> J{Progression to symptomatic PNH?}
  J -- yes --> E
  K[Curative: allo-HCT for refractory or with severe AA] --> L[Reserved for failure of complement therapy or severe AA]

Pearls / Pitfalls

• PNH flow cytometry must include FLAER on granulocytes/monocytes — most sensitive (>0.01 % clones); RBC CD55/CD59 may miss small clones due to ongoing hemolysis (hemolyzed type III RBCs disappear).
• Always check PNH flow in unexplained:
  • Splanchnic vein thrombosis (Budd-Chiari, portal, mesenteric)
  • Aplastic anemia (~50 % have PNH clone)
  • MDS-hypocellular
  • Hemolysis with iron deficiency (chronic Hb urinary loss)
  • Recurrent abdominal pain + dark urine
• Eculizumab / ravulizumab require meningococcal vaccination 2 wk pre-start (ACWY + B) + antibiotic prophylaxis until vaccine response established. Lifelong N. meningitidis infection risk ~1000-fold higher.
• Breakthrough hemolysis on anti-C5 = LDH rises again; usually due to extravascular hemolysis (C3-coated RBCs cleared by spleen/liver) → switch to or add proximal inhibitors (pegcetacoplan, iptacopan, danicopan).
• Anticoagulation for PNH-associated thrombosis is indefinite; warfarin or DOAC; eculizumab dramatically reduces new thrombosis risk.
• PNH causes secondary iron deficiency from chronic urinary Hb loss — supplement iron (oral or IV).
• PNH clones can fluctuate — monitor clone size periodically.
• HCT only curative, but high mortality; reserved for severe AA + PNH or complement-therapy failures.
• PNH in pregnancy: high VTE + pre-eclampsia risk; eculizumab considered safe in pregnancy.
• Anti-FH (Factor H autoantibody) HUS can present similarly — distinguish by flow + complement panel.

Cross-references

• Aplastic anemia overlap
• VTE — splanchnic thrombosis screening
• Thrombophilia — PNH
• aHUS — complement-mediated DDx
• Meningococcal vaccination + ppx

相關題目

• Q-135 — AA — PNH clone monitoring
• Q-136 — PNH — diagnostic flow cytometry
• Q-137 — PNH — eculizumab and breakthrough hemolysis
• Q-138 — PNH — anticoagulation duration

Sources