Increased erythropoietin level induced by hydroxyurea treatment of sickle cell patients

Administration of hydroxyurea in sickle cell disease is associated with a dramatic increase of HbF along with a significant clinical improvement and, occasionally, increased total hemoglobin levels. The underlying mechanisms are not yet fully elucidated.

We report the response of three patients with homozygous sickle cell disease and 10 patients with compound HbS/beta-thalassemia (four with beta(o)thal/HbS and six with beta(+)thal/HbS respectively) to hydroxyurea treatment with regards to their serum erythropoietin levels (sEpo).

Baseline sEpo levels varied from 33.0 to 284.0 IU/L and showed a significant negative correlation with the respective Hb values (P<0.007). Two to three weeks after initiation of treatment, the sEpo values started to increase and reached levels three to 31 times higher than the baseline two to three weeks later. Thereafter, in most cases the Epo values decreased and remained at intermediate levels throughout the rest of hydroxyurea administration, while in a few cases, they returned to baseline. An inappropriate increase of sEpo following treatment with various cytostatic drugs, independently of anemia induced by cytostatic agents, has already been reported in the literature. The cytostatics included cyclophosphamide, anthracyclines, cytosine arabinoside etc., but not hydroxyurea. The results described here with hydroxyurea are virtually similar, ie, they show a significant sEpo increase five to ten days post therapy with no apparent cause. Pulses of high dose Epo have been reported to promote proliferation of erythroid precursors with HbF synthesizing capacity.

Our hypothesis is that a similar phenomenon may occur here also, in the sense that peaks of endogenous Epo may promote proliferation of erythroid precursors which maintain the capacity to synthesize HbF.