Haemolytic uraemic syndrome: SAQ

This boy has typical STEC-associated haemolytic uraemic syndrome. The triad of microangiopathic haemolytic anaemia (haemoglobin of 57 with schistocytes, elevated LDH, undetectable haptoglobin), thrombocytopenia (platelets 42), and acute kidney injury (creatinine 195) following bloody diarrhoea eight days prior, with normal coagulation studies, is diagnostic. The normal prothrombin time and APTT are essential because they distinguish HUS from disseminated intravascular coagulation, where the coagulation cascade is systemically consumed. [1]

Question 1 (10 marks)

Outline your immediate management of this child, including fluid management, blood product support, and the indications for renal replacement therapy. [1]

The overriding principle is meticulous supportive care because no specific therapy reliably alters the course of STEC-HUS. I would first assess and stabilise the airway, breathing, and circulation, with careful attention to fluid balance. This is the most challenging aspect because the child may be volume-depleted from the preceding gastroenteritis but is simultaneously at risk of fluid overload from acute kidney injury. I would assess volume status clinically and with daily weights, input-output charts, and blood pressure monitoring. If the child is volume-depleted and still passing urine, cautious rehydration with isotonic saline is appropriate. If he is oliguric or anuric, I would fluid-restrict to insensible losses plus urine output to prevent pulmonary and cerebral oedema. [1]

For the severe anaemia with haemoglobin of 57 g per litre, I would transfuse packed red cells cautiously, monitoring for volume overload, because rapid expansion of intravascular volume can worsen hypertension and pulmonary oedema. I would avoid routine platelet transfusion because the platelets may be consumed in the microvascular thrombi, potentially worsening the thrombotic process. Platelets are reserved for active bleeding or before invasive procedures such as central line insertion. Fresh frozen plasma is not indicated because coagulation studies are normal. [1]

I would monitor and treat electrolyte disturbances. Hyperkalaemia is common and dangerous: treatment includes calcium gluconate for cardiac stabilisation, insulin-dextrose and salbutamol for intracellular potassium shift, and sodium bicarbonate for metabolic acidosis. The indications for renal replacement therapy are refractory hyperkalaemia unresponsive to medical therapy, severe metabolic acidosis, fluid overload unresponsive to diuretics, and uraemic complications such as pericarditis or encephalopathy. Peritoneal dialysis is the preferred mode in young children, though haemodialysis or continuous renal replacement therapy may be used depending on the clinical context. I would involve the paediatric nephrology team early and transfer to a tertiary centre if dialysis is anticipated. [1]

I would also send stool cultures for E. coli O157:H7 and Shiga toxin PCR, though these may be negative by the time HUS develops. I would avoid antibiotics and antimotility agents. I would screen for neurological involvement, which occurs in 20 to 40 percent of cases and predicts a worse outcome. [1]

Question 2 (10 marks)

Six months later, a 4-year-old girl presents with a similar triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury, but she has no history of diarrhoea and her stool culture is negative. Her C3 is low and she has a maternal aunt with end-stage kidney disease of unknown cause. Her ADAMTS13 activity is 55 percent. Describe how the diagnosis and management differ from the first case, including the role of eculizumab. [2]

This girl has atypical HUS, not STEC-HUS. The key differences are the absence of a diarrhoeal prodrome, the low C3 suggesting complement activation, the family history of end-stage kidney disease suggesting an inherited complement disorder, and the normal ADAMTS13 activity (55 percent) which excludes thrombotic thrombocytopenic purpura. aHUS accounts for 5 to 10 percent of paediatric HUS cases and results from dysregulation of the alternative complement pathway caused by pathogenic variants in complement genes such as factor H, factor I, CD46, factor B, or C3, or by anti-factor H autoantibodies. [2]

The management is fundamentally different from STEC-HUS. While STEC-HUS is managed with supportive care alone, aHUS requires urgent treatment with eculizumab, a humanised monoclonal antibody against complement component C5. Eculizumab blocks the terminal complement pathway, preventing formation of the membrane attack complex (C5b to C9) that damages endothelial cells. The standard dosing for adults and children over 40 kg is 900 mg intravenously weekly for four doses, then 1200 mg every two weeks, with weight-based dosing for children under 40 kg. [2]

The critical management principle is that eculizumab should be started as soon as aHUS is suspected and TTP has been excluded, without waiting for genetic test results. Delay risks irreversible renal damage. Before starting eculizumab, the patient must receive meningococcal vaccination (both conjugated ACWY and serogroup B) and prophylactic penicillin, because terminal complement blockade increases susceptibility to Neisseria meningitidis infection. [2]

Without treatment, aHUS carries 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, with many patients achieving renal recovery. This girl also needs complement genetic testing and counselling about the lifelong risk of relapse, the implications for family members, and the need for prophylactic eculizumab if she ever requires renal transplantation. Both STEC-HUS and aHUS survivors need long-term nephrology follow-up with annual blood pressure and urinalysis, because late-emerging renal sequelae occur in 25 to 40 percent of all HUS survivors. [2]