Overcoming the Barrier

Published - Written by Carla Rothaus

What is the most common risk factor for C. perfringens bacteremia and hemolysis?

The combination of sepsis and a hemolyzed blood specimen should prompt consideration of in vivo hemolysis. Read the Latest NEJM Clinical Problem Solving here.

Clinical Pearls

Q: What infections are associated with intravascular hemolysis?

A: Clostridium perfringens bacteremia can originate from an intraabdominal infection and lead to intravascular hemolysis. Other infections that result in intravascular hemolysis include bartonellosis, malaria, and babesiosis.

Q: Is C. perfringens a common cause of liver abscess?

A: Pyogenic liver abscesses are generally caused by the Streptococcus anginosus group, anaerobic gram-negative bacilli (e.g., bacteroides), Pseudomonas aeruginosa, Escherichia coli, or Klebsiella pneumoniae. A liver abscess caused by C. perfringens is rare. Risk factors include diabetes mellitus, gastrointestinal cancer, and cirrhosis. Most patients present with fever and abdominal pain, although some patients have no localizing symptoms. In one case series involving 20 patients with C. perfringens liver abscesses, all the patients had evidence of intravascular hemolysis at presentation and had rapid growth of C. perfringens in the blood.

Morning Report Questions

Q: What is the most common risk factor for C. perfringens bacteremia and hemolysis?

A: C. perfringens is a spore-forming, anaerobic gram-positive bacillus that is a commensal organism of the gastrointestinal and gynecologic tracts and is also found ubiquitously in soil.  A number of different exotoxins have been described and account for the spectrum of clinical manifestations associated with this organism. Ingestion of a preformed enterotoxin results in self-limited C. perfringens gastroenteritis. The remainder of C. perfringens diseases involve endogenous spore germination and toxin production, which are facilitated by anaerobic conditions (e.g., penetrating trauma or ischemic bowel). The most common example is clostridial myonecrosis, a necrotizing infection of the muscle and soft tissues that usually involves a limb. Bacteremia with toxin production leads to severe sepsis with hemolysis in up to 15% of cases. The exotoxin phospholipase C lecithinase cleaves phospholipids in the red-cell membrane, which leads to an abrupt and severe intravascular hemolysis. Disruption of the gastrointestinal barrier as a result of surgery or cancer is the most common risk factor for C. perfringens bacteremia and hemolysis.

Q: What are some of the causes of in vitro hemolysis?

A: Historically, a laboratory specimen was designated as hemolyzed on the basis of visual inspection after centrifugation, with the color of the serum or plasma serving as a correlate of the concentration of free hemoglobin. A pink tinge develops in mild hemolysis, whereas a reddish-brown color is seen with severe hemolysis, reflecting the higher concentration of free hemoglobin. Increasingly, automated instruments on chemical and coagulation analyzers measure the plasma concentration of free hemoglobin to make this assessment. In vitro hemolysis usually results from factors associated with collection of the blood, such as the prolonged application of a tourniquet, the use of small-bore needles, and sampling from intravenous catheters instead of performing direct venipuncture. Issues with the transport, processing, and storage of blood samples account for a smaller fraction of in vitro hemolysis.

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