Fatal hemolytic uremic syndrome associated with day care surgery and anaesthesia: a case report
© Myrnäs and Castegren; licensee BioMed Central Ltd. 2013
Received: 14 January 2013
Accepted: 24 June 2013
Published: 26 June 2013
Thrombotic angiopathies, i.e. haemolytic uremic syndrome and thrombotic thrombocytopenic purpura, are thought to occur in patients with a combination of risk factors (e.g., an infection with shiga-toxin-producing Escherichia coli (E. coli) or low activity of the metalloproteinase Adamts-13) and a pathophysiological trigger (e.g., anti-endothelial antibodies, cytokines or activation of chemokine receptor 4). To our knowledge, this is the first report describing an association between haemolytic uremic syndrome and routine surgery and anaesthesia.
We present a case in which a 67-year-old Caucasian female developed fatal haemolytic uremic syndrome in the immediate postoperative period of uncomplicated day care surgery. The patient had suffered gastrointestinal symptoms followed by confusion approximately two weeks before surgery, but had been without any symptoms in the week before surgery. Haemolytic uremic syndrome with cerebral symptoms ranging from initial anxiety to subsequent seizures and coma developed within a few hours after the end of surgery. In addition, acute kidney failure and severe thrombocytopenia occurred about the same time. During intensive care, the patient was found to be positive for enterohaemorrhagic E. coli (EHEC) in faeces.
Anaesthesiologists should be notified that haemolytic uremic syndrome is an uncommon differential diagnosis in patients with postoperative seizures and coma. Patients with a recent enterohemmoragic E.Coli infection should be followed postoperatively for signs of haemolytic uremic syndrome.
KeywordsThrombotic microangiopathy Thrombotic thrombocytopenic purpura Plasmapheresis Day care surgery General anaesthesia
Haemolytic uremic syndrome (HUS) is characterised by three prominent attributes: haemolytic anaemia, acute kidney failure and thrombocytopenia . The most common cause of classical HUS (STEC-HUS) is infection with shiga-toxin-producing Escherichia coli (E. coli) 0157:H7. Typically, the incubation period is 3–5 days and approximately 5-15% of infected patients develop HUS. Children are more often affected than adults. Neurological involvement is uncommon . During the German major outbreak of HUS in 2011, patients were infected with E. coli O104:H4. During the outbreak, over 20% of the infected patients developed HUS and 88% of the cases with HUS occurred in adults. Particularly noteworthy was that 68% of the patients were women . Furthermore, neurological involvement was common, whereas the incidence of bloody diarrhoea was infrequent . Neurological symptoms occurred at the same time as there was an increase of lactate dehydrogenase and creatinine and the nadir of the platelet count occurred before the onset of neurological symptoms . The patients needed mechanical ventilation for an average of five days and started to be seizure free after an average of three days .
In patients in whom no infection with shiga-toxin-producing E. coli is found, i.e. atypical HUS (aHUS), mutations in genes encoding proteins of the alternative pathway of the complement system have been identified . A third condition very similar in presentation and pathophysiology, thrombotic thrombocytopenic purpura (TTP), is associated with either a low activity of the metalloproteinase Adamts-13 or antibodies to the protein . All three conditions are sometimes referred to as thrombotic microangiopathies (TMAs) .
In contrast to aHUS, which has a known risk of recurrence following renal transplantation , STEC-HUS is regarded as a unique event not associated with recurrence of the symptoms . In the reports after the 2011 outbreak of STEC-HUS no comments about patients with recurrent presentations were noted [5, 10].
Drug-associated HUS is a commonly acknowledged condition in which the proposed mechanisms are direct endothelial effects or immune-mediated effects associated with deficient Adamts-13 activity . The most commonly implicated drugs are quinine, mitomycin-C, tacrolimus and cyclosporine, as well as platelet-acting drugs, such as clopidogrel and ticlopidine . Other than the most common drugs associated with HUS, reports of a suspected association can be found between the development of HUS and treatment with antibiotics, i.e. penicillin and piperacillin, non-steroidal anti-inflammatory drugs, H2-receptor antagonists and simvastatin .
Adamts-13 protein deficiency is not enough for the development of TTP; rather, a pathophysiological trigger is required for the precipitation of the condition . Anti-endothelial antibodies or cytokines have been proposed as such triggers . An interplay between a predisposing condition and a pathophysiological trigger is most likely also required in STEC-HUS and aHUS, where activation of chemokine receptor 4 (CXCR4/stromal cell-derived factor-1(SDF-1) pathway) has been proposed as a trigger mechanism . Ubiquitin, a natural CXCR4 agonist , is released systemically following trauma and inflammation .
Evidenced-based treatments for TMAs are lacking; however, plasma exchange therapy has been used with varying success . Complement inhibitor treatment with the monoclonal antibody against the compliment protein C5, eculizumab, has been used successfully in recent trials in aHUS .
To our knowledge, there are no publications or case reports describing an association between STEC-HUS with uncomplicated anaesthesia and routine orthopaedic surgery.
Development of the glasgow coma scale and laboratory parameters
Days after surgery
Glasgow coma scale
Haemoglobin (g × L-1)
Platelet count (109 × L-1)
Leukocyte count (109 × L-1)
C-reactive protein (μmol × L-1)
Creatinine (μmol × L-1)
Prothrombin time (INR)
Bilirubin total (μmol × L-1)
Lactate dehydrogenase (μkat × L-1)
The present case of a patient with gastrointestinal symptoms before the onset of HUS and positive PCR of EHEC in faeces is a classic case of HUS. The features of the E. coli being non-serotype O157, verotoxin 2-producing and eae-gene negative, together with the neurological symptoms in an adult female, are uncharacteristic of classical STEC-HUS but similar to the German outbreak of E. coli O104:H4 in 2011 . In this case, the patient had suffered gastrointestinal symptoms followed with transient confusion and recovered from all symptoms over a week prior to surgery. However, in the immediate postoperative period, the cerebral symptoms recurred, only now with rapid deterioration from confusion and agitation to fulminant epileptic seizures and deep coma. The progression from a patient without symptoms before surgery and anaesthesia to fulminant HUS in conjunction with deep unconsciousness took less than 48 h. This close temporal relationship suggests a direct causal effect between the therapy given during surgery and anaesthesia and the recurrence of fulminant HUS. It might be hypothesised that the inflammatory response induced by surgery and anaesthesia activated cell surface receptors (e.g., CXCR4) in a patient at risk of developing HUS because of an EHEC infection, which would hasten the progression of the disease [13–16]. The noteworthy association in time between anaesthesia for uncomplicated surgery and the unique recurrence of STEC-HUS has, to our knowledge, not been described previously.
Anaesthetists and surgeons should be notified of HUS/TTP as an uncommon differential diagnosis of seizures and coma in the postoperative period. Patients with a recent EHEC infection should be followed postoperatively for signs of HUS.
A written informed consent was obtained from the patient’s next of kin for publication of this case report.
Anti-neutrophil cytoplasmic antibody
Chemokine receptor 4
Enterohaemorrhagic e. coli
Glasgow coma scale
Haemolytic uremic syndrome
Shiga-toxin-producing e. coli associated HUS
Magnetic resonance imaging
Polymerase chain reaction
Thrombotic thrombocytopenic purpura.
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