Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease.

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.

Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease.

Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke,making primary stroke prevention a reality. A cross-sectional study of145 Nigerian children aged ≥3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 ±27.0 cm/sec and122 ±22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C cases. Cerebral flow velocities showed a negative correlation with age and hematocrit. Compared with African-American children, Nigerian children with Hb SS disease have a considerably higher prevalence of CR velocities.

Longitudinal decline in lung volume in a population of children with sickle cell disease.

RATIONALE: Sickle cell disease (SCD) results in significant morbidity and mortality attributable to pulmonary complications. The pattern of lung function change across childhood in SCD is not well delineated. OBJECTIVES: To determine if the pattern of lung function in SCD differs from race-matched, predicted values across childhood, to describe that pattern of change, and to examine the effect of clinical covariates on lung function. METHODS: Lung function measurements for children with SCD, aged 8-18 years, from a single center were examined for inclusion. Mixed-model analysis was used to retrospectively review lung function in these children in comparison with those predicted by race-matched reference equations. The contribution of age, sex, Hb level, and beta-globin genotype on longitudinal changes in lung function was examined. MEASUREMENTS AND MAIN RESULTS: Children with SCD show significant decline in spirometric lung volumes across childhood that are concordant with the pattern of change in other measures of lung volume. The average decline for FEV(1) and total lung capacity is 2.93 and 2.15% predicted/year for males and 2.95 and 2.43% predicted/year for females. beta-Globin genotypes known to be associated with more severe disease showed a faster decline in lung function, whereas sex showed an inconsistent effect on lung function. CONCLUSIONS: Lung volumes in children with SCD decline with age. The pattern of decline begins in childhood, and supports a predominately restrictive defect.

Fetal health assessment in pregnancies complicated by sickle hemoglobinopathies.

The contraction stress test (CST) and nonstress test (NST) are used as fetal health assessments. Severe sickle hemoglobinopathies in the parturient have been shown to place the fetus significantly at risk. This study correlates these fetal health assessment tests with outcome data in 58 pregnancies occurring in women with sickle cell disease. There were 30 patients with homozygous sickle cell anemia (HbS-S), 19 with hemoglobin S-C disease (HbS-C), and nine with hemoglobin S-thalassemia (HbS-Thal). All received prophylactic partial exchange transfusions as part of their antepartal care. At 34 weeks' gestation, NSTs followed by CSTs were begun in each patient. A total of 255 tests were performed. Of these, 19 NSTs and 24 CSTs were unsatisfactory or questionably abnormal and were repeated. There were no nonreactive NSTs, and no patient demonstrated a positive CST. The neonatal outcome revealed one infant who was small for gestational age and two infants who were of low birth weight but appropriate for gestational age. All infants survived and were normal. These data suggest that the fetal reactivity and placental reserve among these parturients with severe sickle hemoglobinopathies were uncompromised, as these tests have been shown to be relatively sensitive assessments of fetal well-being in other maternal disorders.

The hemoglobinopathies and pregnancy in Lagos.

Thirty-four patients with abnormal hemoglobin were studied through 42 pregnancies under one obstetrician. There were 30 patients with sickle cell anemia (HbSS), two with sickle cell hemoglobin C disease (HbSC) and two with homozygous hemoglobin C disease (HbCC). There were 39 live births (including one pair of twins), and four perinatal deaths. The patients with HbSC and HbCC had five uncomplicated pregnancies and deliveries. Of the 36 pregnancies in patients with HbSS one aborted at 12 weeks. Intra-uterine growth retardation (14.3%) and pregnancy-induced hypertension (14.3%) were the most serious pregnancy complications. No patient had more than one crisis. Only one out of the 10 patients transfused needed more than two units of blood throughout pregnancy. The mean gestation at delivery was 37.5 +/- 3.2 (S.D.) weeks. The mean birth weight was 2.7 +/- 0.6 (S.D.) kg. The perinatal mortality was 114.3 per thousand live births and there was one maternal death.

Interpretation of lung function tests in the sickle-cell haemoglobinopathies.

Prediction equations have been evolved for the assessment of vital capacity, total lung capacity, and the single breath carbon monoxide transfer factor in haemoglobin SS and haemoglobin SC disease. These relationships take account of the growth disorder and anaemia in the sickle-cell states. The results suggest that, in the clinically stable state, any effects of alveolar capillary sickling and haemoconcentration and any altered reactivity of haemoglobins S and C with the test gas are of no significance for clinical respiratory physiology. Sex differences in lung function appear independent of haemoglobin type.

Discrepancy between pit counting and spleen function tests in nutritional anemias and hemoglobinopathy C.

An increased percentage of erythrocytes with crater-like indentations (pits) when viewed under interference contrast microscopy is accepted as indicative of splenic hypofunction. The percentage of pitted erythrocytes was above the upper limit of the normal range (0.0-3.2%) in 6 patients with megaloblastic anemia (4.6-22.6%), 8 patients with iron deficient anemia (5.6-21.0%) and 6 patients with HbC diseases (12.5-45.0%). However, the spleen function was normal or hyperactive when evaluated by the rate of removal from the circulation of heat-damaged 99mTc-labeled autologous erythrocytes. Thus, in these diseases, there is a discrepancy between pit counting in the peripheral blood and other spleen tests.

Dyserythropoiesis in homozygous haemoglobin C disease.

Electron microscope studies of the bone marrow of three patients with homozygous haemoglobin C (HbC) disease have shown marked ultrastructural abnormalities in several of the polychromatic erythroblasts and marrow reticulocytes and the presence of phagocytosed erythroblasts within the macrophages. Such abnormalities were not found in the bone marrow of three patients with sickle cell anaemia indicating that the abnormalities represented a feature of HbC disease rather than a disturbance secondary to peripheral haemolysis. The characteristic ultrastructural finding in the polychromatic erythroblasts in HbC disease was the presence of grossly-disorganized nuclei showing multiple intranuclear clefts, the loss of parts of the nuclear membrane, oozing of nuclear material into the cytoplasm and an alteration of the structure and stainability of the nuclear chromatin. It is proposed that both the dyserythropoiesis and ineffective erythropoiesis in HbC disease may have resulted from the formation in vivo of very small aggregates of HbC within erythropoietic cells.

Hemoglobin C disease in infancy and childhood.

We reviewed the clinical course, physical findings, and hematologic values in 16 pediatric patients with hemoglobin C disease, all but one identified by a newborn hemoglobinopathy screening program. The patients had a few symptoms or physical findings. Height and weight percentiles were normal. Patients typically had a mild hemolytic anemia characterized by microcytosis and target cells.

Intepretation of lung function tests in the sickle-cell haemoglobinopathies

Prediction equations have been evolved for the assessment of vital capacity, total lung capacity, and the single breath carbon monoxide transfer factor in haemoglobin SS and haemoglobin SC disease. These relationships take account of the growth disorder and anaemia in the sickle-cell states. The results suggest that, in the clinically stable state, and effects of alveolar capillary sickling and haemoconcentration and any altered reactivity of haemoglobins S and C with the test gas are of no significance for clinical respiratory physiology. Sex differences in lung function appear independent of haemoglobin type. (AU)