Haemolytic uraemic syndrome: Case

This boy has typical STEC-associated haemolytic uraemic syndrome. The diagnosis rests on the triad of microangiopathic haemolytic anaemia (haemoglobin of 52 with schistocytes and helmet cells, elevated lactate dehydrogenase, undetectable haptoglobin, negative direct antiglobulin test), thrombocytopenia (platelets 36), and acute kidney injury (creatinine 230), following a bloody diarrhoeal prodrome eight days prior. The normal coagulation studies are critical because they confirm that this is HUS rather than disseminated intravascular coagulation, where the coagulation cascade would be systemically consumed. [1]

Clinical findings

The pattern is unequivocally that of STEC-HUS. The temporal sequence is classic: a five-day episode of bloody diarrhoea resolving three days before the onset of the haematological and renal features, placing the onset of HUS approximately eight days after the start of the prodrome, consistent with the typical 5 to 10 day interval. The haematological picture is that of intravascular haemolysis: schistocytes and helmet cells on the film reflect mechanical fragmentation of red blood cells in partially obstructed glomerular capillaries, the elevated lactate dehydrogenase reflects cell destruction, and the undetectable haptoglobin confirms that free haemoglobin is being released into the plasma. The negative direct antiglobulin test excludes autoimmune haemolysis and is essential for the diagnosis of a microangiopathic process. [1]

The thrombocytopenia is moderate (platelets 36) and reflects platelet consumption in the glomerular microthrombi, not a production problem. The acute kidney injury with elevated creatinine reflects the reduction in glomerular filtration surface area caused by the microvascular obstruction. The hypertension (blood pressure 118 over 78 in a 3-year-old, which is above the 95th centile for age) is driven by renin-mediated vasoconstriction from renal ischaemia and by volume overload from the oliguric renal failure. [1]

Investigations and diagnosis

The diagnosis is typical STEC-associated haemolytic uraemic syndrome. The triad is confirmed by laboratory evidence, and the normal coagulation profile excludes DIC. The key investigations to send are stool culture on sorbitol-MacConkey agar for E. coli O157:H7 and Shiga toxin PCR, though these may be negative because the organism may have been cleared by the time HUS develops. A full complement screen (C3, C4, factor H, factor I, anti-factor H antibodies) and ADAMTS13 activity should be sent to screen for atypical HUS and TTP, though the diarrhoeal prodrome strongly favours STEC-HUS. [1]

The differential diagnosis was considered and excluded. Disseminated intravascular coagulation was excluded by the normal prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer. Thrombotic thrombocytopenic purpura was considered but is less likely given the prominent renal involvement, the diarrhoeal prodrome, and the absence of severe neurological symptoms; an ADAMTS13 level was sent and would be expected to be normal (above 10 percent). Autoimmune haemolysis was excluded by the negative direct antiglobulin test. [1]

Management and outcome

Management began with meticulous supportive care because no specific therapy reliably alters the course of STEC-HUS. Fluid management was the first priority: the child was assessed as mildly volume-depleted from the preceding gastroenteritis but with reduced urine output, so cautious isotonic saline was given with strict monitoring of daily weight, input-output, and blood pressure. The severe anaemia with haemoglobin of 52 was treated with a cautious packed red cell transfusion given slowly over 3 to 4 hours to avoid precipitating pulmonary oedema. Platelet transfusion was withheld because there was no active bleeding and no planned invasive procedure. [1]

Over the next 48 hours, his renal function deteriorated with rising creatinine and worsening oliguria. On day 3 of admission, he developed refractory hyperkalaemia (potassium 7.1 mmol per litre) despite medical management with calcium gluconate, insulin-dextrose, and salbutamol, and peritoneal dialysis was commenced. He received three sessions of peritoneal dialysis over the following week. His neurological status was monitored closely, and he did not develop seizures or altered consciousness. His blood pressure was managed with amlodipine (0.1 mg per kg once daily). Stool culture subsequently grew E. coli O157:H7, confirming STEC-HUS. [1]

Over the second week, his platelet count recovered, his haemoglobin stabilised after two further transfusions, his creatinine fell, and dialysis was discontinued. By day 16, his renal function had returned to near-normal, and he was discharged on amlodipine with a plan for outpatient nephrology follow-up. The family was counselled that even though he appeared to have recovered fully, 25 to 40 percent of STEC-HUS survivors develop late-emerging renal sequelae including proteinuria, hypertension, and reduced glomerular filtration rate, and some progress to end-stage kidney disease years later. He will need annual blood pressure measurement and urinalysis for life. [3]

The counterfactual: if this had been atypical HUS

If this boy had presented with the same triad but no diarrhoeal prodrome, with a low C3 and a family history of renal disease, the management would have been fundamentally different. Atypical HUS requires urgent treatment with eculizumab, a monoclonal antibody against complement C5, started as soon as TTP is excluded by an ADAMTS13 activity above 10 percent, without waiting for genetic test results. The dose would be 900 mg intravenously weekly for four doses, then 1200 mg every two weeks, with meningococcal vaccination and penicillin prophylaxis mandatory before the first dose. Without eculizumab, aHUS has a mortality or end-stage kidney disease rate of 50 to 70 percent. This counterfactual illustrates why 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. [2]