R.Cutting,
J Ng,
E-mail cuttingrobert@hotmail.com
SMJ 2007 52(2): 56
An
86-year-old woman presented to the acute admissions unit with the rapid onset of
jaundice, fever and confusion. During the patients initial assessment a urinary
catheter was passed and a small amount or markedly discoloured urine obtained.
Dip-stick testing was positive for blood but with normal microscopy, indicating
the presence of free haemoglobin in the sample. The condition of the patient
continued to deteriorate with the development of a pyrexia and hypoxia. Urgent
investigations were performed, the results of which are shown in Table
1. The
full blood count demonstrated a marked anaemia with a raised mean cell
haemoglobin concentration (MCHC) and a reduced mean cell volume (MCV). The very
low haematocrit (HCT) with reduced haemoglobin (Hb) indicated that the majority
of the Hb in the sample was free in the plasma rather than contained in red
cells. Renal function and liver function tests were also significantly abnormal
with results consistent with acute renal failure and hepatitis (with a
disproportionately raised bilirubin level) respectively. Radiological
investigations included a chest x-ray (normal) and an abdominal ultrasound,
which revealed echo bright kidneys consistent with acute renal failure with no
other significant pathology noted. As a result of these initial investigations a
blood film was examined and a Direct Antiglobulin Test (DAT or Coombs test)
performed. The blood film demonstrated a marked spherocytosis with some
fragmentation with the DAT being negative. A diagnosis of septicaemia with acute
intravascular haemolysis complicated by acute renal failure was made. The
possibility of Clostridium perfringens infection was included in the
differential diagnosis and a broad-spectrum intravenous antibiotic (cefotaxime)
was commenced after blood cultures had been taken. During the six hours after
admission the patient’s condition continued to rapidly deteriorate,
culminating in a cardio-respiratory arrest. Attempts at resuscitation were
unsuccessful. With the consent of the patient’s family a post-mortem was
requested.
Within 24hours blood culture was positive,
growing Clostridium perfringens. The post-mortem examination findings included;
multiple hepatic abscesses, intense pulmonary and renal congestion, and a
haemorrhagic pericardial effusion. Gram stain and culture of the hepatic
abscesses also demonstrated the presence of Clostridium perfringens.
Clostridium perfringens is a Gram-positive
bacillus with a ubiquitous distribution (including as a commensal in gut flora).
It is a recognised cause of massive intravascular haemolysis, a process that is
thought to be mediated predominantly through the effect of its alpha-toxin,
which can bind to and disrupt the red cell membrane resulting in haemolysis.1
There are a variety of clinical conditions in
which the risk of Clostridium perfringens sepsis is high; examples include
septic abortion,2 gall bladder empyema,3 as a complication
of cholecystectomy,4 with other predisposing conditions including
neoplastic disease (especially of the gastrointestinal and genitourinary tracts)5
but also haematological disease or its therapy.6, 7
occasionally, as in the case described above, no predisposing factor is found8,
although the age of the patient probably made a significant contribution to the
rapid course of the illness. The prognosis is usually poor, with a delay in the
diagnosis and commencement of appropriate antibiotic therapy probably
contributing to this outcome. A high index of suspicion is required and if
appropriate antibiotics, that include activity against anaerobic organisms,
combined with aggressive supportive care is commenced at an early stage, then
resolution of the underlying haemolytic process and patient survival can result.3,
9 The features that suggested the
causative organism included the peripheral blood findings of an acquired DAT
negative spherocytosis (the latter being small cells with concentrated
haemoglobin reflected by a reduced MCV and raised MCHC). The other acquired
causes of spherocytosis include immune (which can be drug, auto and allo-immune
mediated), heat damage (severe burns), snake venoms and rarely severe
hypophosphataemia complicating severe liver disease or acute diabetic
ketoacidosis. Spherocytes (especially microspherocytes) can also complicate
micro-angiopathic haemolysis (MAHA), but usually the other features of MAHA (red
cell fragmentation and thrombocytopenia) are present and are consequent upon
mechanical damage to red cells by isolated or combined effects of endothelial
damage, excess fibrin deposition in the microvasculature, or the shredding of
red cells as they pass over a leaking or damaged mechanical heart valves.10
In summary this case highlights the need to
remember Clostridium perfringens septicaemia in the differential diagnosis of
the acutely septic patient, even if that patient does not fall into one of the
more traditional at risk groups, and also emphasises how examination of the
peripheral blood film can provide valuable information in the evaluation of the
acutely unwell patient.
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