Increased Reticulocytosis during Infancy Is Associated with Increased Hospitalizations in Sickle Cell Anemia Patients during the First Three Years of Life

Objective Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days. Study Design Data from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy and childhood. Results A majority of subjects had demonstrable anemia with increased reticulocytosis. Only increased absolute reticulocyte levels during early infancy were associated with a significant increase in hospitalization during the first three years of life. Higher absolute reticulocyte counts were also associated with a markedly shorter time to first hospitalizations and a four-fold higher cumulative frequency of clinical manifestations over the first three years of life. No significant increase in white blood cell counts was identified among the infant subjects. Conclusions These data suggest that during early infancy, increased reticulocytosis among asymptomatic SCA subjects is associated with increased severity of disease in childhood.

[1]  R. Ware,et al.  A Prospective Pilot Newborn Screening and Treatment Program for Sickle Cell Anemia in the Republic of Angola , 2012 .

[2]  Scott T. Miller,et al.  Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG) , 2011, The Lancet.

[3]  M. Viana,et al.  High reticulocyte count is an independent risk factor for cerebrovascular disease in children with sickle cell anemia , 2011, Pediatric blood & cancer.

[4]  Jeffery L. Miller,et al.  Expression patterns of fetal hemoglobin in sickle cell erythrocytes are both patient‐ and treatment‐specific during childhood , 2011, Pediatric blood & cancer.

[5]  E. Carrol,et al.  Susceptibility to invasive bacterial infections in children with sickle cell disease , 2010, Pediatric blood & cancer.

[6]  Stephen W. Hartley,et al.  Genetic modifiers of the severity of sickle cell anemia identified through a genome‐wide association study , 2009, American journal of hematology.

[7]  C. Quinn,et al.  Improved survival of children and adolescents with sickle cell disease. , 2008, Blood.

[8]  O. Platt,et al.  Hydroxyurea for the treatment of sickle cell anemia. , 2008, The New England journal of medicine.

[9]  C. Quinn,et al.  Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort. , 2008, Blood.

[10]  C. Hillyer,et al.  Transfusion in the patient with sickle cell disease: a critical review of the literature and transfusion guidelines. , 2007, Transfusion medicine reviews.

[11]  A. Schechter,et al.  Fetal hemoglobin silencing in humans. , 2006, Blood.

[12]  Scott T. Miller,et al.  Prediction of adverse outcomes in children with sickle cell disease. , 2000, The New England journal of medicine.

[13]  Scott T. Miller,et al.  Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. , 1998, The New England journal of medicine.

[14]  R. Hebbel,et al.  CD36-positive stress reticulocytosis in sickle cell anemia. , 1996, The Journal of laboratory and clinical medicine.

[15]  C. Pegelow,et al.  Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. , 1995, Blood.

[16]  G. Bray,et al.  Assessing clinical severity in children with sickle cell disease. Preliminary results from a cooperative study. , 1994, The American journal of pediatric hematology/oncology.

[17]  S. Davies,et al.  Bone marrow transplantation for sickle cell disease. , 1993, Archives of disease in childhood.

[18]  A. Schechter,et al.  Levels of fetal hemoglobin necessary for treatment of sickle cell disease. , 1988, The New England journal of medicine.

[19]  E Vichinsky,et al.  Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. , 1986, The New England journal of medicine.

[20]  D. Higgs,et al.  Acute splenic sequestration in homozygous sickle cell disease: natural history and management. , 1985, The Journal of pediatrics.

[21]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[22]  G. Serjeant,et al.  The Development of Haematological Changes in Homozygous Sickle Cell Disease: a Cohort Study from Birth to 6 Years , 1981, British journal of haematology.

[23]  H. Pearson,et al.  Physiologic anemia of the newborn infant. , 1971, The Journal of pediatrics.

[24]  R. P. Spencer,et al.  Functional asplenia in sickle-cell anemia. , 1969, The New England journal of medicine.

[25]  D J Weatherall,et al.  Inherited haemoglobin disorders: an increasing global health problem. , 2001, Bulletin of the World Health Organization.

[26]  W. Rosse,et al.  The cooperative study of sickle cell disease: review of study design and objectives. , 1982, The American journal of pediatric hematology/oncology.