Haemolytic uraemic syndrome: Viva

Branch 1: Diagnosis and the defining triad

The candidate should recognise that this girl has haemolytic uraemic syndrome and state the defining triad: microangiopathic haemolytic anaemia (haemoglobin of 54 with schistocytes, reflecting intravascular fragmentation), thrombocytopenia (platelets of 38, reflecting platelet consumption in microthrombi), and acute kidney injury (creatinine of 210, reflecting glomerular microvascular obstruction). A strong candidate should emphasise that the normal coagulation studies are essential to the diagnosis because they distinguish HUS from disseminated intravascular coagulation, where the prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer would all be deranged. [1]

If the examiner asks about the cause, the candidate should explain that approximately 90 percent of paediatric HUS follows Shiga toxin-producing Escherichia coli gastroenteritis, most commonly the O157:H7 strain. The temporal relationship is critical: the bloody diarrhoea preceded the HUS by about one week, which is the classic interval. The candidate should explain the pathophysiology: Shiga toxin binds to globotriaosylceramide receptors on glomerular endothelial cells, causing endothelial injury, complement activation, and platelet-rich microthrombi formation that block the glomerular capillaries and mechanically fragment red blood cells. [1]

If the examiner presses on differential diagnosis, the candidate should distinguish HUS from thrombotic thrombocytopenic purpura, which has the same microangiopathic haemolytic anaemia and thrombocytopenia but predominantly neurological rather than renal involvement, no diarrhoeal prodrome, and an ADAMTS13 activity below 10 percent. The distinction matters because TTP requires urgent plasma exchange, which is not routinely indicated for STEC-HUS. [3]

Branch 2: Acute management and supportive care

If asked about immediate management, the candidate should state clearly that there is no specific therapy for STEC-HUS and that meticulous supportive care is the treatment. The candidate should address fluid management first, explaining that this is the most challenging aspect because the child may be volume-depleted from gastroenteritis but is simultaneously at risk of fluid overload from acute kidney injury. The approach is to assess volume status carefully and resuscitate with isotonic crystalloid if depleted while monitoring daily weights and urine output, but to fluid-restrict to insensible losses plus urine output if the child is oliguric or anuric. [1]

The candidate should address blood product support precisely. Severe anaemia with haemoglobin below 60 to 70 g per litre warrants cautious packed red cell transfusion, given slowly to avoid precipitating pulmonary oedema. Platelet transfusion should be avoided unless there is active bleeding or a procedure is planned, because the transfused platelets may be consumed in the microvascular thrombi and worsen the thrombotic process. This is a classic exam trap that the examiner may probe. [1]

The candidate should state the indications for renal replacement therapy: refractory hyperkalaemia, severe metabolic acidosis, fluid overload unresponsive to diuretics, and uraemic complications. Peritoneal dialysis is preferred in young children. The candidate should mention that antibiotics and antimotility agents should be avoided in STEC infection because they may increase Shiga toxin release or prolong gut carriage. Plasma exchange is not routinely indicated for STEC-HUS because trials have not shown benefit. [1]

Branch 3: The diarrhoea-negative scenario and atypical HUS

If the examiner changes the scenario to a child with the same triad but no diarrhoeal prodrome, the candidate should shift to considering atypical HUS. The candidate should state that aHUS accounts for 5 to 10 percent of cases and results from dysregulation of the alternative complement pathway due to pathogenic variants in complement genes or anti-factor H autoantibodies. The candidate should list the clues: no diarrhoeal prodrome, low C3, family history of HUS or end-stage kidney disease, relapsing course, or neonatal onset. [2]

The candidate should describe the management change: eculizumab, a humanised monoclonal antibody against complement C5, is the definitive first-line therapy for aHUS. The dose is 900 mg intravenously weekly for four doses, then 1200 mg every two weeks for adults and children over 40 kg, with weight-based dosing for smaller children. The critical principle is that eculizumab should be started as soon as aHUS is suspected and TTP has been excluded by ADAMTS13 activity above 10 percent, without waiting for genetic test results. Before the first dose, the patient must receive meningococcal vaccination and penicillin prophylaxis because terminal complement blockade increases susceptibility to Neisseria meningitidis infection. [2]

A strong candidate should address the prognosis and long-term implications. Without treatment, aHUS has a mortality or end-stage kidney disease rate of 50 to 70 percent, and recurrence after renal transplant exceeds 80 percent without prophylactic eculizumab. With early eculizumab, outcomes are dramatically improved. The candidate should also state that all HUS survivors, whether STEC-HUS or aHUS, need lifelong nephrology follow-up with annual blood pressure and urinalysis because late-emerging renal sequelae occur in 25 to 40 percent of survivors. The candidate should close by emphasising that the single most important decision in HUS is distinguishing STEC-HUS from aHUS, because it determines whether supportive care alone or urgent complement blockade is needed. [3]