Yolanda Rooks

Fever in young children with sickle cell disease.

Bacterial septicemia and meningitis are major causes of death in young children with sickle cell anemia. We report a prospective study of 182 episodes of fever among 22 children with sickle cell diseases identified at birth. The majority of patients with fever exceeding 39.5 degrees C were treated with antibiotics intravenously until results of blood cultures were known. Infectious diseases were documented in 38% of all febrile events. Six episodes of bacterial septicemia, two associated with meningitis, were successfully treated with no mortality or residual morbidity. These data form the basis of suggestions for management of the young child with sickle cell disease and fever.

Pre- and postnatal growth and development in sickle cell anemia.

I T IS G E N E R A L L Y A C C E P T E D that homozygous sickle ce l l disease impairs physical growth during childhood. Although previous studies have reported conflicting results concerning the timing and extent of this impaired growth, the general pattern in childhood appears to consist of prepubertal deficits in height, weight, and skeletal maturation and delayed puberty. 1-a Adults with Hb SS remain thin but achieve normal, or even supranormal, height? There has been little information regarding cognitive development in children with Hb SS; Neel 5 has reported deficits similar to those in black children with other sorts of chronic illness. All previous studies of growth and development in children with Hb SS have been cross-sectional in design, thus raising some important methodological questions. Some have not used control groups and have based their conclusions on normative standards. Since no children were followed from birth, the high mortality and morbidity of sickle cell disease during the early months and years of life 6 probably resulted in a lack of data based on the most severely affected children. In addition, since Hb SS can occasionally result in a relatively mild clinical course, it is likely that some less severely affected patients were not included in such studies. It seems likely that available

645 INTERFERENCE PHASE MICROSCOPIC ENUMERATION OF PITTED RBC AND SPLENIC HYPOFUNCTION IN SICKLE CELL ANEMIA

Functional hyposplenia contributes to overwhelming infection in SS disease and may be assessed by Howell-Jolly bodies and ≥ scans. H.J. bodies are rare (<1/105 RBC), and scans involve radiation. By interference phase microscopy, many RBC of asplenic individuals show surface craters or “pits.” 31 children with SS disease, 0-20 years of age, and various controls were studied.Preliminary results suggest that >3.0% pitted RBC correlate with negative scans and H.J. bodies. Negative correlation between HbF and % pits and positive correlation between age and % pits were noted. In patients with Hb SS disease, there is a gradual, rather than abrupt, loss of splenic activity over many years. Functional hyposplenia is associated with an intermediate number of pitted RBC compared to anatomic asplenia. This technique is non-invasive, non-isotopic and semi-quantitative. It nay help date the onset of risk of severe infection and may be useful in determining a strategy for prophylaxis against severe bacterial infections.

621 GROWTH AND DEVELOPMENT IN CHILDREN WITH SICKLE CELL TRAIT: A MATCHED-PAIR PROSPECTIVE STUDY

To remove the methodologic flaws of studies claiming that sickle cell trait (Hb AS) impairs physical growth and cognitive development, we prospectively investigated 25 matched pairs (50 subjects) of Black children chosen from a cord blood electrophoresis screening program. For each child with Hb AS, an Hb AA child was matched at birth for sex, birth date, birth weight, gestational age, 5′ Apgar score, and socioeconomic status. At ages 3-5 years, each child was evaluated, within one month of his match, by persons “blind” to the hemoglobin genotype. The results are shown below, together with Pα (probability of no difference) and Pβ (probability of missing a true AA-AS difference as large as Δ):These results, which demonstrate that 3-5 year-old children with sickle cell trait have no deficits in standard measures of growth and development, emphasize the importance of rigorous methodology when clinical groups are assembled and compared.

934 THE TWO-HOUR SICKLE CELL PREP (SCP) FOR RAPID DETERMINATION OF SICKLE HEMOGLOBIN (HB S)

A rapid and accurate means of determining the percentage of Hb S in blood would be of value in the management of sickle cell patients undergoing emergency exchange transfusions and on chronic transfusion programs. To determine the usefulness of the 2-hour SCP in predicting the % Hb S we compared the % of sickled cells in blood incubated for 2 hours in sodium metabisulfite to the % Hb S simultaneously determined by column chromatography (Sickle Cell Quik Column Method, Helena Laboratory.) Seventeen blood samples from 6 transfused patients with homozygous sickle cell disease were studied. Combined data from the 17 samples revealed a mean (±SEM) % of sickled cells determined by the 2-hour SCP of 30±6 and a mean % Hb S by column of 30±5. There was no significant difference between the two values as determined by the paired T-test (p=.96). Comparison of the two methods on individual samples revealed that 8 determinations by the 2-hour SCP were higher than those obtained by the column method, while 7 were lower. The discrepancy between the two methods on individual samples was usually less than 10 percentage points, although 6 samples had differences of 10-18 percentage points. We conclude that the 2-hour SCP is a simple, reliable, and accurate method of estimating the % Hb S and can be used as a guide in the management of sickle cell patients undergoing transfusion therapy.

361 CORD BLOOD SCREENING FOR SICKLE HEMOGLOBINS: EVIDENCE FOR FEMALE PREPONDERANCE OF HEMOGLOBIN S

Since June, 1972, we have conducted a comprehensive umbilical cord blood screening program for sickle hemoglobinopathies at Yale-New Haven Hospital. When we recently noticed an apparent preponderance of females with hemoglobins AS and SS, we decided to analyze the results of the first 65 months of screening. An FAS hemoglobin pattern (sickle cell trait) was detected in 162/1959 black females vs. 129/2017 in black males (X2=5.14,P<.05). For the FS hemoglobin pattern (sickle cell anemia and sickle β-thalassemia), the difference was even more striking: 15/1959 in black females vs. 4/2017 in black males (X2=6.73,P<.01). For 704 Puerto Rican newborns, the incidence of sickle cell trait was very low (2.1% overall), and there were no significant female-male differences.Excluding the two children with FS cord blood electrophoreses who were subsequently shown to have sickle β-thalassemia, there were 17 black newborns with hemoglobin SS among the first 3976 black births since the inception of the screening program. This represents an incidence of 1 in 234 live births, which far exceeds the 1 in 750 predicted by the Hardy-Weinberg equation. The excess of observed over predicted SS newborns is almost entirely accounted for by the high incidence in black females, 1 in 150. Hemoglobin S may confer a selective advantage in utero that is more marked in females.

646 FETAL AND NEONATAL CORRELATES OF SICKLE CELL ANEMIA

In the Hgb S homozygote, sickle hemoglobin is present at 12-16 weeks of gestation and accounts for 10-20% of the Hb at birth. In the neonate with sickle cell anemia, about 10% of circulating RBC can be induced to sickle and isolated instances of neonatal morbidity and mortality have been ascribed to sickling. 34 infants with SS disease were diagnosed by cord blood Hb electrophoresis, performed on all black infants at our hospitals. At Yale, stillbirths are also studied. The number of patients exceeded that predicted by gene frequency, making it unlikely that any cases were missed. Neonatal physical measurements and clinical courses were reviewed retrospectively. 32/34 infants were AGA with respect to birthweight, length and head circumference. 5/34 infants had gestational ages <38 weeks and weighed <2500 gm. One postmature and one premature were SGA. 4/34 had 1 min. APGARs <8, but all were >8 at 5 min. 7/34 developed clinical jaundice. In 2 cases, ABO EBF was proven; 4 others were premature. Phototherapy was used in 4 cases. No regular transfusions or exchange transfusions were performed. No infants developed sepsis. Hospital stay was prolonged only in the prematures. None of these patients had significant morbidity which could be ascribed to sickling, and there were no neonatal deaths. Therefore, these data do not indicate very important consequences of SS disease during gestation or in the neonatal period.