Makindo Medical Notes

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

⚠️ Important: HUS is often triggered by E. coli 0157:H7 producing Shiga toxin. Antibiotics 🚫 and antimotility drugs 🚫 should be avoided as they worsen outcomes. Mortality is highest in the elderly, due to intravascular haemolysis 🩸, thrombocytopenia 🩸, and acute kidney injury (AKI) ⚡. Severe cases may require plasma exchange 🔄 or haemofiltration 💧.

📖 Overview

• HUS = triad of microangiopathic haemolytic anaemia (MAHA) 🩸, thrombocytopenia 🩸, and acute kidney injury (AKI) ⚡.
• RBC fragmentation → anaemia; platelet consumption → bleeding risk; renal microthrombi → AKI.

🧬 Aetiology

• Most common in children (after diarrhoea 💩) or elderly (with AKI).
• Verocytotoxin-producing E. coli (VTEC), esp. strain 0157:H7 🦠.
• Adults: may follow drug exposure (e.g. ciclosporin, quinine).
• Familial HUS: deficiency of Factor H (a complement regulator) ➡️ uncontrolled complement activation.

⚙️ Pathophysiology

• Shiga toxin damages endothelium → renal microvascular thrombosis 🧱.
• Platelet activation + aggregation → thrombocytopenia 🩸.
• Shear stress in narrowed vessels → RBC fragmentation ✂️ (schistocytes).

📊 Classification: Diarrhoea vs No Diarrhoea

• D+ HUS (95%): Diarrhoea-associated, typically post-E. coli infection in children 👧. ADAMTS13 levels usually normal.
• D- HUS (5%): Atypical form (aHUS) due to complement dysregulation 🌀. Affects all ages; often recurrent and more severe.

Haemolytic Uremic Syndrome (HUS) is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury (AKI). It can be classified into typical (D+), atypical (D−), and secondary forms.

🧪 Types of Haemolytic Uraemic Syndrome (HUS)

⚠️ UK Clinical Pearls

• 🧪 Notifiable disease: STEC/E. coli O157 must be reported to public health.
• 👶 Children: HUS is the leading cause of AKI in children in the UK – urgent paediatric nephrology input required.
• 💉 Transfusions: Red cells often needed; avoid platelet transfusion unless life-threatening bleeding.
• 📊 Monitoring: Daily U&E, FBC, BP, and strict fluid balance are essential.
• 🌱 Prognosis: Mortality <5% in children with D+ HUS; poorer in atypical/secondary forms (risk of ESRD).

Comparison — HUS vs TTP

🧾 Causes of Atypical HUS (D-)

• 💊 Medications: Mitomycin C, Ticlopidine, Cyclosporine, Tacrolimus, Quinine
• Combination chemotherapy 💉
• Radiotherapy ☢️ or congenital causes 🧬
• Malignancy: prostate, gastric, pancreatic cancers 🎗️
• Connective tissue disease: scleroderma, antiphospholipid syndrome 🤲

🔍 Differential Diagnosis

• DIC vs HUS: DIC shows abnormal coagulation (↑ PT/APTT, ↓ fibrinogen). HUS → coagulation profile remains normal ✅.

⚡ Clinical Features

• Prodrome: gastroenteritis with bloody diarrhoea 💩.
• Signs: jaundice 🟡, pallor 😓, bruising/petechiae 🔴.
• Red/brown urine ⚫, rash, hypertension 📈, uraemia 🧪.
• Mostly children, but also seen in adults (esp. aHUS).

🔬 Investigations

• FBC: Anaemia (Hb < 8 g/dL), thrombocytopenia 📉.
• Blood film: Schistocytes ✂️, polychromasia.
• Biochemistry: ↑ LDH, ↑ unconjugated bilirubin, ↓ haptoglobin.
• Coagulation profile: PT/APTT/fibrinogen normal (distinguishes from DIC ✅).
• Stool culture: Look for E. coli 0157:H7 🦠.
• Kidney biopsy: Consider if diagnosis uncertain or severe disease 🧾.
• ADAMTS13: Typically normal in HUS (reduced in TTP).

🩺 Management

• Immediate care: Specialist unit transfer 🚑. Avoid antibiotics 🚫, antimotility drugs 🚫, and routine platelet transfusions 🚫.
• Renal support: Dialysis required in ~50% of AKI cases 💧. Up to 85% recover renal function in D+ HUS ✅.
• Plasma exchange: Daily plasmapheresis with FFP is treatment of choice in severe/atypical HUS 🔄.
• Adjuncts: If refractory, consider agents like eculizumab 💉 (complement inhibitor, esp. for aHUS). Steroids are not effective 🚫.
• Supportive: Manage hypertension 💊, anaemia (transfusion if necessary), fluids ⚖️.
• Prognosis: Most children recover 🌱, but atypical HUS has poorer outcomes and high recurrence risk ⚠️.

📚 References

• NICE CKS – Haemolytic Uraemic Syndrome
• UpToDate – HUS overview
• Diagnostic Approach to Microangiopathic Haemolytic Disorders

Cases — Haemolytic Uraemic Syndrome (HUS)

• Case 1 — Typical (Post-Diarrhoeal HUS): A 4-year-old boy develops bloody diarrhoea after eating undercooked beef at a barbecue. A week later, he presents with pallor, oliguria, and petechiae. FBC shows Hb 6.5 g/dL, platelets 40 ×10⁹/L, creatinine 240 µmol/L. Blood film: fragmented RBCs (schistocytes). Stool culture positive for E. coli O157:H7. Diagnosis: Typical HUS.
• Case 2 — Atypical HUS (Complement-Mediated): A 25-year-old woman presents with hypertension, oliguria, and microangiopathic haemolytic anaemia. No diarrhoeal prodrome. Family history reveals her mother required dialysis in her 30s. Complement studies show low C3. Genetic testing later confirms complement factor H mutation. Diagnosis: Atypical HUS (genetic complement dysregulation).
• Case 3 — Secondary HUS (Drug-Associated): A 60-year-old man treated with gemcitabine for pancreatic cancer presents with anaemia, thrombocytopenia, and acute kidney injury. Blood film shows schistocytes; LDH markedly elevated. No diarrhoeal prodrome. Diagnosis: Secondary HUS induced by chemotherapy.

Teaching Commentary 🧬

HUS is defined by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. - Typical HUS follows Shiga toxin–producing E. coli infection in children. - Atypical HUS arises from uncontrolled complement activation (often genetic). - Secondary HUS may be triggered by drugs (gemcitabine, quinine), pregnancy, or autoimmune disease. On blood film, schistocytes are key. Management differs: typical HUS is supportive (dialysis, fluids, no antibiotics or antimotility drugs), while atypical HUS may respond to eculizumab (anti-C5 monoclonal antibody). Prognosis is excellent in children with typical HUS, but atypical/secondary forms carry higher relapse and renal failure risk.