Dialysis patients treated with EPO often show a substantial drop in
hematocrit during a severe bacterial infection, even when prompt
antibiotic treatment is given. Is there any evidence that an immediate
increase in EPO dosage can mitigate this problem? Has anyone developed a
rational strategy?
Karl G Prutz, MD
(Department of Medicine, Helsingborg, Sweden)
Response by Steven Fishbane, M.D., (Winthrop University Hospital, Mineola, NY)
Patients treated with recombinant human erythropoietin (rHuEPO) develop an
acquired resistance to the drug's erythropoietic effect during episodes of
infection. The hematocrit may decrease rapidly despite early administration
of appropriate antibiotics. It is unclear whether the acute decrease in
hematocrit is associated with an adverse outcome. In general the hematocrit
rises quite rapidly after the infection has resolved.
The etiology of infection induced rHuEPO resistance is incompletely
understood. Recently,
Allen et al
reported that interferon gamma may mediate
acquired rHuEPO resistance due to inflammation. An alternative explanation, however, may instead be
related to
deranged iron metabolism. During an episode of infection, the body sequesters
iron in the reticuloendothelial system, and erythropoietic tissue is
temporarily deprived of iron. From the teleologic perspective, this appears
to be an adaptive response. Microorganisms are highly reliant on iron as a
growth factor. When infected the human body transiently "sacrifices" optimal
erythropoiesis in favor of blocking access of microorganisms to the body's
iron supply.
The optimal strategy for utilizing rHuEPO during infections is unclear. There
is no evidence that an abrupt increase in rHuEPO dose would prevent a drop in
hematocrit. It is our policy to continue rhuEPO at the dose administered
prior to the infection. If the hematocrit decreases (which usually occurs
quite rapidly) the rHuEPO dose is adjusted upwards. We have experimented with
empiric intensive intravenous iron administration during infection, and have
not found it to be effective.
(September, 1996)