Ware et al identified factors associated with a significant increase in fetal hemoglobin in children with sickle cell anemia following hydroxyurea therapy. The authors are from multiple Children's hospitals in the United States.


The goal of hydroxyurea therapy is to increase the percent hemoglobin F in red blood cells. An increase in hemoglobin F is associated with:

(1) fewer painful, vasocclusive events

(2) fewer episodes of acute chest syndrome

(3) reduced early mortality.


In children treated with hydroxyurea the quartile with the highest response had a mean hemoglobin F percentage of 26%, with an absolute increase from baseline of +16% (indicating a mean baseline level of 10% hemoglobin F).


Mild myelosuppression (as manifested by reductions in white blood cells and reticulocytes while minimizing anemia) is associated with maximal hemoglobin F response.


Factors associated with optimum hemoglobin F response:

(1) maximum tolerated dose of hydroxyurea in mg per kg per day

(2) excellent compliance

(3) low reticulocyte count, decreased from baseline

(4) low white blood cell count, decreased from baseline

(5) high hemoglobin level, increased from baseline

(6) high MCV (macrocytosis), increased from baseline


Although response data is shown in Table 2 (page 13), it shows the mean response for quartiles, which makes implementation difficult. The following will be used to guestimate cutoffs for the implementation.


Mean Values for Highest Quartile

maximum tolerated daily dose

26.9 mg/kg



absolute reticulocyte count with therapy

135,000 per µL

change in reticulocyte count from baseline

decrease by 272,000 per µL

absolute WBC count with therapy

7,400 per µL

change in WBC count from baseline

decrease by 7,400 per µL

hemoglobin level with therapy

10.2 g/dL

change in hemoglobin from baseline

increase by 2 g/dL

MCV with therapy

107 fL

change in MCV from baseline

increase by 21 fL


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