September 01, 2011
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Early plasma exchange therapy led to prompt recovery in HUS patients

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Researchers from Denmark found that early plasma exchange therapy successfully managed and accelerated healing among adults with diarrhea-associated hemolytic uremic syndrome, according to new findings published in The Lancet.

“Our study was able to assess the benefit of plasma exchange in a large outbreak of hemolytic uremic syndrome (HUS), such assessment might be difficult in a randomized controlled trial because of the rarity of the disease,” Edin Colic, MD, of Odense University Hospital in Odense, Denmark, and colleagues wrote in the study. “Early plasma exchange might ameliorate the course of diarrhea-associated HUS in adults, but this finding should be verified in randomized controlled trials.”

In the observational study, Colic and colleagues examined five patients aged 44 to 70 years residing in southern Denmark. HUS cases were identified between May 25 and May 28 and were caused by Shiga toxin-producing Escherichia coli (STEC) serotype O104:H4. All patients reported visiting Germany during the E. coli foodborne outbreak.

Patients were treated with daily plasma exchange by centrifugation and substitution with fresh frozen plasma. Stool culture and serological testing were conducted, and researchers calculated changes in platelet count, glomerular filtration rate and lactate dehydrogenase to determine the success of management with plasma exchange therapy.

Plasma exchange rapidly increased median platelet count and glomerular filtration rate, decreased median lactate dehydrogenase concentration and improved neurological status to the extent that all patients were discharged with normal neurological status within 7 days (range, 5-8 days) of plasma exchange, according to the study.

Early start of plasma exchange after onset of bloody diarrhea accelerated healing, according to lactate dehydrogenase concentrations and platelet counts for individual patients as a function of the time interval between onset of bloody diarrhea and plasma exchange,” according to the researchers. “We identified an inverse correlation between this time interval and the reduction of lactate dehydrogenase concentrations by plasma exchange (P=.02).”

Piero Ruggenenti, MD, and Giuseppe Remuzzi, MD, FRCP, both of the Aldo and Cele Daccò Clinical Research Centre for Rare Diseases, Mario Negri Institute for Pharmacological Research in Bergamo, Italy, wrote in an accompanying editorial that: “Several mechanisms might account for the effectiveness of plasma exchange, including, in typical HUS, early toxin removal from the circulation. Add-on treatment with eculizumab, an antibody against the C5 component of the complement system, could have been considered to inhibit the uncontrolled complement activation that amplifies vascular damage on Shiga-toxin exposure.

“At present, early plasmapheresis, with or without eculizumab, remains the cornerstone of treatment,” they wrote. “Whether early treatment with carbapenems or antimicrobials that are electively effective against extended-spectrum beta-lactamase-producing E. coli (fosfomycin) could help to prevent progression from enterocolitis to HUS might merit formal investigation.”

For more information:

  • Colic E. Lancet. 2011;doi:10.1016/S0140-6736(11)61145-8.
  • Ruggenenti P. Lancet. 2011;doi:10.1016/S0140-6736(11)61217-8.

Disclosure: The researchers report no relevant financial disclosures.

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