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)

Seen with E. coli strain 0157:H7, which can cause endothelial damage, initiating the process. Avoid the use of antibiotics or antimotility agents, as these have been shown to worsen the severity of the condition. Mortality is high, especially in the elderly, due to intravascular haemolysis, thrombocytopenia, and acute kidney injury (AKI). Some patients may require plasma exchange or haemofiltration.

Overview

• Microangiopathic haemolytic anaemia (MAHA) – characterized by red cell fragmentation.
• Thrombocytopenia and acute kidney injury (AKI).

Aetiology

• Common in children or elderly patients with acute renal failure.
• Often caused by verocytotoxin-producing E. coli (VTEC), especially strain 0157:H7.
• Can occur in adults due to endothelial damage from drugs.
• Familial (congenital) HUS – caused by deficiency of Factor H, a complement-regulating plasma protein synthesized by the liver.

Pathophysiology

• Toxins cause endothelial damage → leading to renal microvascular thrombosis.
• Activation of the blood coagulation cascade → platelet aggregation → consumptive thrombocytopenia.
• Mechanical damage to RBCs as they pass through occluded microcirculation.

Classification: Diarrhoea Status

• With Diarrhoea (D+): Accounts for 95% of haemolytic uraemic syndrome (HUS) in children, typically caused by Shiga toxin-associated HUS (Stx-HUS) from E. coli 0157:H7. ADAMTS13 levels are usually normal.
• Without Diarrhoea (D-): Atypical form 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-)

• Mitomycin C, ticlopidine.
• Cyclosporine, tacrolimus, quinine.
• Combination chemotherapy.
• Radiotherapy, congenital causes.
• Malignancies (prostate, gastric, pancreatic cancer).
• Scleroderma, antiphospholipid syndrome.

Differential Diagnosis

• Disseminated Intravascular Coagulation (DIC): Can behave similarly, but DIC involves coagulopathy.
• In HUS, PT, APTT, and fibrinogen levels remain normal, unlike in DIC.

Clinical Features

• Initial gastroenteritis symptoms due to E. coli infection.
• Most common in children.
• Jaundice, easy bruising, and pallor due to anaemia.
• Bloody diarrhoea, red or brown urine.
• Petechial rash, malaise, hypertension, and uraemia.

Investigations

• Anaemia (Hb < 8 g/dl) and low platelets.
• Blood film shows schistocytes (fragmented or helmet-shaped RBCs).
• Signs of intravascular haemolysis: elevated LDH, reticulocytes, bilirubin; low haptoglobin.
• Negative Coombs test.
• Acute kidney injury: elevated urea and creatinine levels.
• Normal PT, APTT, D-dimer, and fibrinogen levels.
• Stool samples should be cultured for E. coli 0157:H7.
• Kidney biopsy may be required to assess the extent of renal damage.
• ADAMTS13 levels are typically normal in HUS.

Management

• Immediate transfer to a specialist unit.
• Avoid antibiotics, antimotility agents, and platelet transfusions.
• Renal failure often requires dialysis (50% of patients), although 85% may fully recover.
• Supportive care for hypertension and anaemia.
• Daily plasma exchange (plasmapheresis with fresh-frozen plasma) is the treatment of choice.
• For unresponsive cases, vincristine or cyclosporine A may be used; steroids are not effective.
• Most children recover fully with supportive care, though severe cases can lead to irreversible renal damage or death.
• Prognosis is poorer for D- (atypical) HUS patients, often adults, due to underlying conditions.

References

• Diagnostic Approach to Microangiopathic Haemolytic Disorders