What is the immediate treatment for Hemolytic Uremic Syndrome (HUS)?

Immediate Treatment for Hemolytic Uremic Syndrome (HUS)

Begin immediate supportive care while urgently distinguishing between STEC-HUS (Shiga toxin E. coli) and atypical HUS (aHUS), as this determines whether complement inhibitor therapy with eculizumab is required—a life-saving intervention for aHUS that must not be delayed. 1, 2, 3

Emergency Diagnostic Workup (Obtain Immediately)

The following tests must be ordered stat to guide treatment decisions:

• Complete blood count with peripheral blood smear for schistocytes (>1% supports TMA diagnosis, but absence does not exclude it) 1, 2, 4
• ADAMTS13 activity level to exclude thrombotic thrombocytopenic purpura (TTP)—if <10%, this is TTP requiring plasma exchange, not HUS 1, 2, 4
• Stool testing for Shiga toxin/verocytotoxin-producing E. coli (VTEC/STEC) to distinguish typical from atypical HUS 1, 2
• Hemolysis markers: LDH (elevated), haptoglobin (reduced), indirect bilirubin (elevated), direct Coombs test (negative) 1, 2
• Renal function: creatinine, urinalysis for hematuria and proteinuria 1, 2
• Complement testing: C3, C4, CH50, AP50 (for aHUS evaluation) 1, 4

Immediate Supportive Management (All HUS Types)

Initiate these measures immediately while awaiting diagnostic results:

• Fluid and electrolyte management with careful monitoring of volume status 5, 6, 7
• Antihypertensive therapy for blood pressure control 5, 6
• Red blood cell transfusions only for symptomatic anemia or hemoglobin <7-8 g/dL in stable patients—do not transfuse more than minimum necessary 1, 4
• Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy 1, 4
• Initiate renal replacement therapy (dialysis) when indicated for acute kidney injury 5, 6, 7
• Avoid antidiarrheal medications and consider avoiding antibiotics in suspected STEC-HUS 6

Critical Decision Point: STEC-HUS vs Atypical HUS

STEC-HUS (Typical HUS) Indicators:

• Diarrhea onset 4-5 days BEFORE HUS symptoms 2
• Positive stool VTEC/STEC testing 1, 2
• Management: Supportive care only—eculizumab is NOT indicated and FDA-labeled specifically states it is not for STEC-HUS 3, 5

Atypical HUS (aHUS) Indicators:

• Negative VTEC testing OR short diarrhea period OR simultaneous onset of diarrhea and HUS 2
• ADAMTS13 activity >10% (excludes TTP) 1, 2
• Management: Requires immediate complement inhibitor therapy 1, 3

Specific Treatment for Atypical HUS (Medical Emergency)

Do not delay eculizumab therapy while awaiting genetic testing results—genetic mutations are found in only 50-60% of cases, and treatment delay increases mortality and irreversible organ damage. 1

Eculizumab Dosing for Adults (≥18 years):

• Induction: 900 mg IV weekly for 4 weeks 3
• Week 5: 1200 mg IV (one week after 4th dose) 3
• Maintenance: 1200 mg IV every 2 weeks thereafter 3

Mandatory Meningococcal Prophylaxis:

• Vaccinate against meningococcal serogroups A, C, W, Y, and B at least 2 weeks before first eculizumab dose if possible 1, 3
• If urgent therapy cannot be delayed: Administer vaccines immediately AND provide antibacterial prophylaxis (long-term penicillin) 1, 3
• Monitor for early signs of meningococcal infection throughout treatment—this is a life-threatening risk with complement inhibition 3

Pediatric aHUS Dosing (<18 years):

Weight-based dosing differs significantly from adults:

• ≥40 kg: Same as adult dosing 3
• 30-<40 kg: 600 mg weekly × 2 doses, then 900 mg at week 3, then 900 mg every 2 weeks 3
• 20-<30 kg: 600 mg weekly × 2 doses, then 600 mg at week 3, then 600 mg every 2 weeks 3
• 10-<20 kg: 600 mg × 1 dose, then 300 mg at week 2, then 300 mg every 2 weeks 3
• 5-<10 kg: 300 mg × 1 dose, then 300 mg at week 2, then 300 mg every 3 weeks 3

Monitoring Treatment Response

Assess response by tracking these parameters every 2-4 weeks initially:

• Platelet count normalization (target >150,000/mm³) 1
• Resolution of hemolysis (LDH normalization, disappearance of schistocytes) 1
• Stabilization or improvement in renal function (serum creatinine) 1
• Complete blood count with differential 1, 4

Critical Pitfalls to Avoid

• Never delay eculizumab in suspected aHUS while awaiting genetic testing—only 50-60% have identifiable mutations 1
• Never discontinue eculizumab prematurely—carries 10-20% risk of relapse with potential renal failure 1
• Never dismiss diagnosis based on "rare" schistocytes alone—low sensitivity of this test, especially early in disease 2, 4
• Never give platelet transfusions routinely—may worsen microangiopathy 1, 4
• Never use eculizumab for STEC-HUS—FDA-labeled contraindication, not indicated 3

Special Clinical Contexts

Pregnancy-Associated aHUS:

• Initiate eculizumab immediately—C5 inhibitors have been instrumental in resolving TMA in pregnancy-triggered aHUS 1

Pediatric Considerations:

• In children <1 year: Test for complement-unrelated genes (DGKE, WT1) and consider methylmalonic acidemia with homocystinuria (MMACHC) 2
• HUS may present with incomplete triad in up to 50% of pediatric cases at onset—do not wait for all three features 1, 2

Neurological Involvement (10-20% of aHUS cases):

• Obtain neurology consultation, EEG, and brain MRI with FLAIR/T2 sequences if motor symptoms, weakness, vision changes, seizures, or encephalopathy present 2
• Look for bilateral symmetric hyperintensities in basal ganglia, cerebral peduncles, caudate nuclei, putamen, thalami, hippocampi, insulae, or brainstem 2

Plasma Exchange Consideration

For aHUS, eculizumab has replaced plasma exchange as standard of care—plasma therapy is now historical treatment with inferior outcomes compared to complement inhibition 1, 5, 6, 7, 8

However, if eculizumab is unavailable and aHUS is confirmed:

• Fresh frozen plasma contains factor H at physiological concentrations and may induce remission in some cases 6
• Supplemental eculizumab dosing required if plasma exchange is performed concurrently 3