Is This a Hemolytic Transfusion Reaction?

Christopher M. Lough, MD; Leonard I. Boral, MD, MBA; Julie Ribes, MD


December 11, 2013

In This Article

Clostridium perfringens Sepsis

Sepsis with severe intravascular hemolysis is a rare but deadly complication of infection with C perfringens. Reported mortality rates are 70%-100%.[6]

Seeding of the bacteria most often occurs from the gastrointestinal tract, biliary tract, or uterus, with hemolysis complicating the sepsis in 7%-15% of cases.[7] Disease progression is very rapid, with death often occurring in less than 24 hours.

The C perfringens organism produces a series of toxins, of which the alpha toxin, a lecithinase, has the ability to destroy the red cell membrane and cause spherocytosis, which leads to hemolysis.[8] Rapid death is a consequence of the 7-minute doubling time of this organism.[9]

Early diagnosis and treatment are critical to any chance of survival. Debridement of identifiable gangrenous tissue and high-dose intravenous penicillin are the current recommended treatments.[7] Exchange transfusion is being examined as a mechanism to improve prognoses in these patients.[8]

In our patient, an infectious etiology was not initially suspected. Despite the negative DAT, suspicion was high for an acute immune hemolytic transfusion reaction, a cold agglutinin, or an improperly collected specimen. By the time the organism was identified, the patient had already died. Intravenous antibiotics were never initiated in this case.

No autopsy was performed, so the source of the infection was not discovered. However, the patient had 2 reasons for significant immunosuppression: long-standing treatment with dexamethasone and lenalidomid (both are highly immunosuppressive), and the innate immunosuppression caused by multiple myeloma.

A possible source of the C perfringens might have been a break in the gastric mucosa, causing ulceration and permitting entrance of the bacteria into the bloodstream. Long-standing steroid therapy (eg, dexamethasone) is a well-known cause of gastric ulceration. There has been some association with C perfringens sepsis and leukemia,[7] but no literature has implicated multiple myeloma.

When a patient presents with intravascular hemolysis, early consideration of clostridial sepsis is crucial to initiating the appropriate antibiotic treatment as soon as possible. A negative DAT is also a critical step in the decision tree of how to work up these cases.


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