6 7 2 Editorial correspondence The Journal of Pediatrics October 1995

Risk of infection in children with hemoglobin S-beta-thalassemia To the Editor:

We read with interest the article by Lynch and Tobias, 1 who re- ported life-threatening infection in hemoglobin S-[3-thalassemia. They describe two atypical patients and then suggest the need for more aggressive management of all febrile illnesses in children with this diagnosis. In this era of cost containment, caution must be ex- ercised before accepting anecdotal cases as the basis for global management recommendations. We recently reviewed the literature and could find no documented case of pneumococcal bacteremia in this disorder. Moreover, we have encountered only one patient with pneumococcal bacteremia (who recovered without sequelae) during 176 patient-years of follow-up of our center's 39 pediatric patients with hemoglobin S-[3-thalassemia. 2

The hemoglobin electrophoresis in patient 1 exhibits no hemo- globin A2, an elevated level of which is usually seen in double het- eroZygotes for hemoglobin S and [3-thalassemia. Further, the mean corpuscular volume of 94.6 fl is too high and hematocrit of 0.15 too low for this condition. These hematologic findings suggest that their patient had sickle cell anemia, with the 7% hemoglobin A resulting either from a prior blood-transfusion or laboratory error.

Streptococcus pneumoniae septicemia is common in patients with sickle cell anemia but would not be expected in children with hemoglobin S-[3-thalassemia, whose splenic function is normal or near normal. 3, 4 A follow-up hemoglobin electrophoresis, blood count, and family studies (if possible) should be provided before this case can be accepted as the first example of overwhelming septi- cemia in hemoglobin S-[3-thalassemia. No change in current man- agement strategies for fever in pediatric patients with hemoglobin S-[3-thalassemia are warranted on the basis of this report.

Zora R. Rogers MD George R. Buchanan, MD Department of Pediatrics

University of Texas Southwestern Medical Center at Dallas Dallas, TX 75235-9063

9/35/67460

REFERENCES

1. Lynch A, Tobias JD. Life-threatening infection in two children with hemoglobin S-beta-thalassemia. J PEDIATR 1995;126: 581-2.

2. Rogers ZR, Buchanan GR. Bacteremia in children with sickle hemoglobin C disease and sickle-beta + thalassemia: Is pro- phylactic penicillin necessary? J PEDIATR 1995; 127:348-54.

3. Barrios NJ, Kirkpatrick DV, Lohman D, et al. Spleen function in children with sickle [3+ thalassemia. J Natl Med Assoc 1991; 83:819-22.

4. Pearson HA, Gallagher D, Chilcote R, et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediat- rics 1985;76:392-7.

Reply To the Editor:

Our patient 1 had no prior history of blood transfusions that might have invalidated his hemoglobin electrophoresis, although fol- low-up studies would easily confirm the diagnosis. Undoubtedly, there is a great deal of variability among patients with heterozygous hemoglobinopathies. Further studies evaluating greater numbers of these patients will be needed to make recommendations regarding the collective group.

Amy Lynch, MD Division of Pediatric Critical Care

Vanderbilt Univ. Medical Center North T-Ol18

Nashville, TN 37232-2591 9/35/67461

Efficacy and cost analysis of treating low birth weight infants with erythropoietin To the Editor:

We read with interest the article by Obls et al. (J PEDIATR 1995;126:421-6) concerning the efficacy and cost benefit of treat- ing very low birth weight infants with erythropoietin (Epo) during the first 2 weeks of life. Some concerns in the article preclude any realistic conclusions.

There are instances where the results claim statistical signifi- cance, yet calculations of the p value suggest otherwise. For exam- ple, 20% of Epo patients and 70% of placebo recipients required transfusions during the first 20 days (a primary oucome variable of this study). In the text, this conferred significance ofp <0.01, in Ta- ble II the calculation resulted in p <0.05, but in a two-tailed Fisher Exact Test with 10 patients per group (done on Instat statistical software, Graph Pad, Inc., San Diego, Calif.), p = 0.07. Further- more, it was found that a higher percentage of Epo recipients (40%) than placebo recipients (20%) received no transfusions during the hospitalization, and the statistics suggestedp <0.05. Nonetheless, on our calculation this p value equals 0.62. Finally, it was suggested that lactate values increased in the placebo group compared with the Epo group (p <0.05), but using a Student t test, p = 0.66. These er- rors are critically important to the conclusions of this study.

Another concern relates to the power calculation. The authors point out that 32 patients are needed to show a difference of 2 + 2 transfusions.-What does the 2 _+ 2 represent? Is this a difference of 0 to 4 transfusions between groups? Between patients? Is this out- come clinically significant? This needs to be clarified, because with this very small sample size a type I error is possible.

It is stated that the total cost of transfusions in the placebo recip- ients was $2030, yet the charge per patient was $255.55. If there are stilI 10 patients in this group, the charge per patient should be $203. We also question the charge of $100.00 for 10 doses (200 units/kg