Haemolytic Uraemic syndrome (HUS)

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:H7.60 which may cause endothelial damage which may initiate the process. Avoid antibiotics or antimotility agents as they have been shown to worsen the severity. Mortality is high in HUS in the elderly due to intravascular haemolysis, low platelets and AKI and some need plasma exchange or haemofiltration

About

• Microangiopathic haemolytic anaemia - red cell fragmentation
• Thrombocytopenia and Acute kidney injury

Aetiology

• Seen in Children or elderly with acute renal failure
• Verocytotoxin-producing E.coli (VTEC) e.g. E. coli strain 0157:H7.60.
• Seen in adults due to drugs that damage endothelial cells
• Familial (congenital) HUS - deficiency of factor H a plasma protein synthesised by the liver, which regulates the complement pathway.

Pathophysiology

• Toxin ↑ Endothelial cell damage ↑ renal microvascular thrombosis
• ↑ activation of the blood coagulation cascade.
• ↑ Platelet aggregation results in a consumptive thrombocytopenia.
• ↑ Mechanical damage to RBCs circulating through partially occluded microcirculation.

Classification: There are two forms depending on Diarrhoea

• With Diarrhoea (D+) may be bloody diarrhoea - 95% of cases of haemolytic uraemic syndrome in children and infants due to E. coli strain 0157:H7.60. This is called Shiga toxin-associated haemolytic-uraemic syndrome (Stx-HUS). Usually normal ADAMTS13,
• Without Diarrhoea (D-) atypical form. There may be a deficiency in the metalloprotease ADAMTS13 as seen in TTP. Seen at all ages. Poorer prognosis. This a complement-mediated TMA (CM-TMA; also known as atypical HUS) that is due to a hereditary or acquired defect in a complement regulatory protein. May have slightly low levels of ADAMTS13

Causes of D- HUS

• Mitomycin C, ticlopidine
• Cyclosporine, tacrolimus, quinine
• Combination chemotherapy
• Radiotherapy, Congenital
• Malignancies - prostate, gastric, pancreatic
• Scleroderma, Antiphospholipid syndrome

Differentials

• DIC can behave similarly but there will be a coagulopathy
• HUS the PT, APTT and fibrinogen levels are normal

Clinical

• Gastroenteritis picture initially were due to E.Coli
• Presents in Children
• Jaundice, easy bruising and pallor from anaemia
• Bloody diarrhoea. Red/Brown urine
• Petechial rash, Malaise, Hypertension, Uraemia

Investigations

• Anaemia Hb < 8 g/dl ↓ platelets
• Blood film - schistocytes. Fragmented, deformed, irregular, or helmet-shaped RBCs
• Intravascular Haemolysis ↑ LDH ↑ Reticulocytes ↑ Bilirubin ↓ Haptoglobin
• Coombs test results are negative
• Acute kidney injury ↑ Urea and ↑ Creatinine
• Normal PT, APTT, D-dimer and fibrinogen levels
• Stool samples will be cultured for E.coli 0157:H7
• Kidney biopsy may be indicated to see the degree and nature of kidney damage
• Normal ADAMTS-13 levels

Management

• Transfer to specialist Unit. Avoid antibiotics or antimotility agents as they have been shown to worsen severity. Avoid platelet transfusions.
• Renal failure often requires dialysis in 50% of patients. However, 85% can go on to make a full recovery.
• Supportive management of hypertension, anaemia.
• Daily Plasma exchange (plasmapheresis combined with fresh-frozen plasma replacement) is currently the treatment of choice
• Unresponsive cases have been treated with vincristine or cyclosporine A. No role for steroids.
• With appropriate supportive care, affected children often recover completely
• Irreversible renal damage and death can occur in more severe cases.
• Prognosis in D- patients, usually adults is usually poorer as there is an underlying cause

References

• Diagnostic approach to microangiopathic hemolytic disorders