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)

In cases of HUS, infection with E. coli strain 0157:H7 can cause endothelial damage, triggering a cascade that leads to microangiopathic haemolytic anaemia (MAHA). Avoid using antibiotics or antimotility agents in these patients, as these therapies have been shown to worsen the clinical course. Mortality is high—especially in the elderly—due to complications such as intravascular haemolysis, thrombocytopenia, and acute kidney injury (AKI). Some patients may require plasma exchange or haemofiltration.

Overview

• HUS is characterized by microangiopathic haemolytic anaemia (MAHA) with red cell fragmentation.
• Thrombocytopenia and acute kidney injury (AKI) are common findings.

Aetiology

• Most commonly seen in children (with diarrhea) or elderly patients with acute renal failure.
• Infection with verocytotoxin-producing E. coli (VTEC), especially strain 0157:H7.
• Can also occur in adults due to endothelial damage from drugs.
• Familial (congenital) HUS deficiency of Factor H, a complement-regulating protein produced by the liver.

Pathophysiology

• Toxins cause endothelial damage, leading to renal microvascular thrombosis.
• Activation of the coagulation cascade results in platelet aggregation and consumptive thrombocytopenia.
• Mechanical shear stress in occluded microcirculation leads to red blood cell fragmentation.

Classification: Do they have Diarrhoea

• 95% of cases associated With Diarrhoea (D+): Accounts for approximately 95% of HUS cases in children. Typically caused by Shiga toxin-associated HUS (Stx-HUS) from E. coli 0157:H7. ADAMTS13 levels are usually normal.
• 5% Without Diarrhoea (D-): Represents an atypical form of HUS (aHUS) due to defects in complement regulation, affecting all ages. This complement-mediated thrombotic microangiopathy (CM-TMA) often presents with low ADAMTS13 levels.

Causes of Atypical HUS (D-)

• Medications: Mitomycin C, Ticlopidine, Cyclosporine, Tacrolimus, Quinine
• Combination chemotherapy
• Radiotherapy and congenital causes
• Malignancies: Prostate, Gastric, and Pancreatic cancers
• Connective tissue diseases: Scleroderma, Antiphospholipid syndrome

Differential Diagnosis

• Disseminated Intravascular Coagulation (DIC): Although DIC can present similarly, it is distinguished by abnormal coagulation parameters. In HUS, PT, APTT, and fibrinogen levels remain normal.

Clinical Features

• Initial gastroenteritis symptoms due to E. coli infection.
• Predominantly affects children, but can occur in adults.
• Features include jaundice, easy bruising, and pallor due to anaemia.
• Patients may experience bloody diarrhoea, red or brown urine, and a petechial rash.
• Other associated findings: malaise, hypertension, and uraemia.

Investigations

• FBC: Reveals anemia (Hb typically < 8 g/dL) and thrombocytopenia.
• Blood Film: Demonstrates schistocytes (fragmented or helmet-shaped RBCs) and polychromasia.
• Biochemical Markers: Elevated LDH and unconjugated bilirubin; low serum haptoglobin.
• Coagulation Profile: Normal PT, APTT, D-dimer, and fibrinogen levels help distinguish HUS from DIC.
• Stool Cultures: Culture for E. coli 0157:H7 should be performed.
• Kidney Biopsy: May be indicated to assess the extent of renal damage in severe cases.
• ADAMTS13 Levels: Typically normal in HUS.

Management

• Immediate Care: Transfer the patient to a specialist unit promptly. Avoid the use of antibiotics, antimotility agents, and unnecessary platelet transfusions.
• Renal Support: Dialysis is often required in cases of acute kidney injury (approximately 50% of patients), although up to 85% may fully recover renal function.
• Plasma Exchange: Daily plasma exchange (plasmapheresis with fresh-frozen plasma) is the treatment of choice, particularly in severe cases.
• Adjunctive Therapies: For cases unresponsive to plasma exchange, agents such as vincristine or cyclosporine A may be considered. Steroids are generally not effective.
• Supportive Care: Manage hypertension and anaemia with appropriate supportive measures.
• Prognosis: Most children recover fully with supportive care, though severe cases can lead to irreversible renal damage or death. The prognosis is poorer for atypical (D-) HUS, which often affects adults with underlying conditions.

References

• Diagnostic Approach to Microangiopathic Haemolytic Disorders