Hemolytic Uremic Syndrome (HUS) is a serious condition characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). It is most commonly triggered by Shiga toxin-producing Escherichia coli (STEC-HUS), but other causes exist. Below is a concise overview of HUS, including its pathophysiology, causes, clinical features, diagnosis, and management, tailored to provide a clear understanding.
Pathophysiology
- Mechanism:
- HUS involves endothelial damage, typically in small blood vessels (microvasculature), especially in the kidneys.
- Damage leads to:
- Microangiopathic hemolytic anemia: Red blood cells (RBCs) are fragmented (schistocytes) as they pass through damaged vessels.
- Thrombocytopenia: Platelets are consumed in microthrombi formation.
- AKI: Renal microvascular thrombosis and inflammation impair kidney function.
- Key Trigger (STEC-HUS):
- Shiga toxin (from E. coli O157:H7 or other strains) binds to endothelial cells, causing cell injury and activating the coagulation cascade.
- Other Forms:
- Atypical HUS (aHUS): Caused by complement dysregulation (genetic mutations or autoantibodies).
- Secondary HUS: Triggered by drugs, infections (e.g., HIV), or systemic diseases.
Causes
- Typical HUS (STEC-HUS):
- Most common, especially in children.
- Associated with Shiga toxin-producing E. coli (e.g., O157:H7) from contaminated food (undercooked beef, leafy greens) or water.
- Less commonly, Shigella dysenteriae.
- Atypical HUS (aHUS):
- Caused by complement system dysregulation (e.g., mutations in CFH, CFI, or MCP genes).
- May be triggered by infections, pregnancy, or drugs.
- Secondary HUS:
- Infections: HIV, Streptococcus pneumoniae, influenza.
- Drugs: Chemotherapy (e.g., gemcitabine), immunosuppressants (e.g., cyclosporine), quinine.
- Systemic Diseases: Systemic lupus erythematosus (SLE), malignancy.
- Pregnancy-Related: Postpartum or preeclampsia-associated.
- Other Rare Causes:
- Cobalamin C deficiency (metabolic disorder).
- Genetic mutations (e.g., DGKE gene).
Clinical Features
- Prodrome (STEC-HUS):
- Bloody diarrhea, abdominal pain, and fever 3–7 days after E. coli exposure.
- Classic Triad:
- Hemolytic Anemia: Fatigue, pallor, jaundice; schistocytes on blood smear.
- Thrombocytopenia: Bruising, petechiae, or bleeding.
- Acute Kidney Injury: Oliguria, anuria, edema, hypertension, or uremia.
- Other Symptoms:
- Neurological: Seizures, confusion (due to microthrombi or uremia).
- Cardiac: Hypertension or heart failure (from fluid overload).
- Gastrointestinal: Persistent abdominal pain (STEC-HUS).
Diagnosis
- Clinical Suspicion:
- Triad of anemia, thrombocytopenia, and AKI, especially after bloody diarrhea (STEC-HUS).
- Family history or recurrent episodes suggest aHUS.
- Laboratory Findings:
- CBC:
- Anemia (low hemoglobin, e.g., <10 g/dL).
- Thrombocytopenia (platelets <150,000/µL).
- Peripheral Smear: Schistocytes (fragmented RBCs), helmet cells.
- Renal Function:
- Elevated creatinine and BUN.
- Electrolyte imbalances (e.g., hyperkalemia, hyponatremia).
- Hemolysis Markers:
- Elevated lactate dehydrogenase (LDH).
- Low haptoglobin.
- Indirect hyperbilirubinemia.
- Urinalysis: Hematuria, proteinuria.
- Stool Culture/PCR: Detects STEC (E. coli O157:H7) in typical HUS.
- Complement Testing (for aHUS):
- Low C3, normal C4, or genetic testing for complement mutations.
- CBC:
- Differential Diagnosis:
- Thrombotic Thrombocytopenic Purpura (TTP): Distinguished by low ADAMTS13 activity (<10%) and prominent neurological symptoms.
- Disseminated Intravascular Coagulation (DIC): Abnormal coagulation (low fibrinogen, high D-dimer).
- Other Microangiopathies: Malignant hypertension, scleroderma.
Management
- Supportive Care (STEC-HUS):
- Fluid and Electrolyte Management:
- Correct dehydration carefully to avoid fluid overload.
- Manage hyperkalemia, acidosis, or uremia.
- Dialysis: For severe AKI (oliguria, uremia, or electrolyte imbalances).
- Blood Transfusions: For severe anemia (hemoglobin <6–7 g/dL); avoid over-transfusion.
- Hypertension Control: ACE inhibitors or calcium channel blockers.
- Avoid Antibiotics (in STEC-HUS): May increase Shiga toxin release, worsening HUS.
- Avoid Anti-Motility Agents: Increase toxin retention in STEC-HUS.
- Fluid and Electrolyte Management:
- Atypical HUS (aHUS):
- Eculizumab:
- Monoclonal antibody against C5, blocking complement activation.
- First-line for confirmed aHUS; dramatically improves outcomes.
- Plasma Exchange: Temporarily used if eculizumab is unavailable or diagnosis is unclear (also removes autoantibodies).
- Immunosuppression: For aHUS with autoantibodies (e.g., anti-CFH antibodies).
- Kidney Transplant: May be needed for end-stage renal disease (ESRD); recurrence risk in aHUS.
- Eculizumab:
- Secondary HUS:
- Treat underlying cause (e.g., stop offending drug, treat infection).
- Supportive care similar to STEC-HUS.
- Monitoring:
- Daily renal function, CBC, and LDH.
- Watch for complications (e.g., seizures, heart failure).
Prognosis
- STEC-HUS:
- Most children recover with supportive care; ~5–10% mortality in severe cases.
- ~20–30% develop chronic kidney disease (CKD) or hypertension.
- aHUS:
- Higher risk of ESRD without eculizumab.
- Relapses common without ongoing complement inhibition.
- Secondary HUS: Prognosis depends on underlying cause.
Key Points
- HUS is a triad of hemolytic anemia (schistocytes), thrombocytopenia, and AKI.
- Causes: STEC-HUS (most common, post-diarrhea), aHUS (complement dysregulation), or secondary (drugs, infections).
- Diagnosis: Confirmed by labs (schistocytes, high LDH, low platelets, elevated creatinine) and stool PCR for STEC.
- Management: Supportive care for STEC-HUS; eculizumab for aHUS; treat underlying cause in secondary HUS.
- Avoid: Antibiotics in STEC-HUS; unnecessary plasma exchange in confirmed STEC-HUS.
Disclaimer: owerl is not a doctor; please consult one.
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