溶血性尿毒症候群

Buzzwords → Dx

Diagnostic Criteria

• Triad: MAHA + thrombocytopenia + AKI.
• STEC-HUS: Shiga-toxin-producing E. coli (O157:H7 classic; O104:H4 outbreak strain) confirmed by stool culture or PCR; preceding bloody diarrhea.
• aHUS: No Shiga-toxin trigger; ADAMTS13 ≥10 % (rules out TTP); complement testing (C3, C4, factor H, factor I, MCP) and genetic panel (CFH, CFI, MCP, C3, CFB, DGKE, THBD).
• Workup ALWAYS includes:
  • Stool: shiga-toxin / EHEC PCR
  • ADAMTS13 activity
  • Complement: CH50, C3, C4, factor H/I/B, anti-factor H autoantibody
  • Genetic panel for aHUS

Workup

• CBC + smear (schistocytes), DAT (negative).
• LDH, haptoglobin, indirect bili, retic (hemolysis).
• Cr, BUN, urinalysis (AKI ± proteinuria).
• ADAMTS13 activity + inhibitor (rules out TTP).
• Stool studies: Shiga-toxin EIA + PCR + culture; recent diarrhea history.
• Complement panel + genetic testing for aHUS.
• Pregnancy test + obstetric workup if female reproductive age.
• Autoimmune workup: ANA, anti-dsDNA if SLE features.
• Bone marrow + flow if cytopenias atypical.
• Drug review for TMA-associated agents.

Treatment Algorithm

flowchart TD
  A[Suspected TMA] --> B[CBC + smear + Cr + LDH + ADAMTS13<br>+ stool Shiga toxin]
  B --> C{ADAMTS13 result + clinical?}
  C -- ADAMTS13 <10% --> D[See TTP — TPE + caplacizumab + steroids]
  C -- ADAMTS13 ≥10% + diarrhea --> E[STEC-HUS]
  C -- ADAMTS13 ≥10% no diarrhea --> F[aHUS — start eculizumab empirically<br>before genetic confirmation in severe cases]
  E --> G[Supportive care<br>NO antibiotics<br>NO antimotility agents<br>fluids + RBC/platelet support<br>dialysis if AKI severe]
  F --> H[Eculizumab 900 mg IV q1wk × 4<br>then 1200 mg q2wk maintenance<br>or ravulizumab q8wk maintenance]
  H --> I[Vaccination: meningococcal ACWY + B + PCV13 + HiB<br>ANTIBIOTIC PROPHYLAXIS until vax established]
  I --> J{Genetic confirmation?}
  J -- pathogenic CFH/CFI/CFB/C3 --> K[Lifelong therapy or trial discontinuation if stable + low-risk genotype]
  J -- MCP / DGKE pathogenic --> L[Time-limited therapy possible]
  J -- no mutation --> M[Likely autoantibody; immunosuppression + eculizumab]

Pearls / Pitfalls

• STEC-HUS — NO antibiotics: kill bacteria → release more Shiga toxin → worsens HUS. Supportive care only. Antimotility agents also harmful (delay toxin clearance).
• aHUS — ECULIZUMAB / RAVULIZUMAB anti-C5 is curative. Start empirically in severe cases before genetic confirmation; diagnose meningococcal vaccination + antibiotic prophylaxis (high meningococcal infection risk).
• Pneumococcal HUS: neuraminidase exposes T-antigen → IgM autoantibody → MAHA + AKI. Avoid plasma transfusions (contain anti-T-antigen) — washed RBCs/platelets if needed.
• Drug-induced TMA: calcineurin inhibitors, gemcitabine, mitomycin C, quinine, ticlopidine — discontinue offender, supportive care, eculizumab if persistent.
• Pregnancy / postpartum TMA with normal ADAMTS13 → consider aHUS (high complement-mediated risk peripartum). Differential: HELLP, AFLP, pre-eclampsia, sepsis.
• Cobalamin C deficiency in infants: methylmalonic acid + homocystinuria + HUS — treat with B12 + betaine.
• Plasma exchange has historical role in aHUS but is largely replaced by eculizumab/ravulizumab for genetic aHUS. PEX is still useful when complement therapy unavailable.
• Renal recovery after STEC-HUS is usually complete; ~5 % progress to ESRD. aHUS recovery depends on complement therapy timing.
• Renal transplant in aHUS has high recurrence — CFH/CFI mutations often need pre-emptive eculizumab. MCP mutations have lower recurrence (membrane-bound, donor kidney protected).

Cross-references

• TTP — DDx by ADAMTS13
• MAHA — broader framework
• DIC — coagulation-active TMA mimic
• Eculizumab + meningococcal prophylaxis
• Thrombocytopenia Workup

相關題目

• Q-094 — HUS — STEC vs aHUS distinction
• Q-095 — aHUS — eculizumab and meningococcal prophylaxis
• Q-096 — HUS — pneumococcal HUS in child

Sources