Gillian H Maude

Acute splenic sequestration in homozygous sickle cell disease: natural history and management.

Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period. The age at first attack ranged from 3 months to 6 years. Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.225 by 2 years, and 0.265 by 3 years, and 0.297 by 5 years of age. Thirteen events were fatal, 11 during the first attack, and all before transfusion could be instituted. Recurrences occurred in 49% of survivors of the first attacks, and there were diminishing intervals between subsequent events. Respiratory symptoms were associated with 52 of 132 events, but bacterial isolates on blood culture were less frequent, and ASS was not prevented by pneumococcal vaccine or penicillin prophylaxis. A high fetal hemoglobin level protected against attacks of ASS. A parental education program aimed at early diagnosis of ASS was followed by an increase in the incidence rate for ASS from a mean of 4.6 per 100 patient-years to 11.3 per 100 patient-years, probably reflecting increased awareness of the complication. During the same periods, the fatality rate fell from 29.4 per 100 events to 3.1 per 100 events. The improvement in outcome is likely to have resulted from improvement in medical management and earlier detection of ASS.

Clinical presentation of homozygous sickle cell disease

The pattern of initial clinical symptoms and signs developing in a representative sample of 305 children with homozygous sickle cell (SS) disease diagnosed at birth was analyzed. Specific symptoms were present by age 6 months in 6% of the group, and had developed by the first to eighth birthdays in 32%, 61%, 78%, 86%, 90%, 92%, 94%, and 96%, respectively. Inclusion of nonspecific symptoms in the analysis led to earlier recognition by a mean of 3 months in the first year and by a mean of approximately 1 year between the ages of 2 and 4 years. Dactylitis was the most common initial symptom, noted in 40% of the group overall and in 50% in the first 2 years. Painful crisis was the first symptom in more than one fourth of the patients and was the most frequent symptom after the age of 2 years. Acute splenic sequestration led to presentation in one-fifth of the group overall and in one third of patients younger than 2 years. The most common nonspecific symptom was pneumonia. There was a significant trend of earlier presentation in children with low fetal hemoglobin levels. The age at presentation did not appear to be affected by alpha-thalassemia status.

Pregnancy in Jamaican women with homozygous sickle cell disease. Fetal and maternal outcome

Summary. The outcome of 664 pregnancies in 297 Jamaican women with homozygous sickle cell (SS) disease over the period 1959–1984 was reviewed. Overall, the spontaneous abortion rate was 118 per 1000 pregnancies, the stillbirth rate 128 per 1000 births, and perinatal mortality 171 per 1000 births. There was a striking secular increase in both spontaneous abortions and stillbirths which was accounted for, in part, by a trend for abortions to increase with maternal age up to the age of 30 years, a greater proportion of patients in the high‐risk 25–29 year age group occurring in the 1980–1984 period. Another factor contributing to the poor obstetric performance in the 1980–1984 period was probably an increased survival and pregnancy rate in high‐risk patients. Seven women had pregnancy‐related deaths giving a pregnancy mortality rate of 1·1%.

Clinical presentation of sickle cell-hemoglobin C disease

Early symptoms were observed in a representative sample of 166 children with sickle cell-hemoglobin C disease diagnosed at birth. Symptoms were uncommon in the first year of life; in approximately 50% specific symptoms had developed by 5 years, but 22% remained without specific symptoms to 10 years. The age at presentation was significantly earlier in patients with low hemoglobin F levels, but was not influenced by heterozygous alpha-thalassemia-2. Painful crisis was the initial manifestation in 77% of the children; other symptoms included dactylitis (14%) and pneumococcal septicemia and acute splenic sequestration (4% each). The commonest nonspecific symptom was acute chest syndrome. The relatively mild early clinical course of sickle cell-hemoglobin C disease indicates that neonatal diagnosis does not have the same urgency as for homozygous sickle cell disease.

Topical antibiotics in chronic sickle cell leg ulcers

A randomized, controlled, trial of a topical antibiotic preparation (neomycin, bacitracin, and polymyxin B) was performed in 30 patients with homozygous sickle cell (SS) disease and chronic leg ulceration. Over a period of 8 weeks, the reduction in ulcer size was significantly (P less than 0.05) greater in the treatment group than in the control group. The results suggest that these topical antibiotics may contribute to the therapy of chronic leg ulceration associated with sickle cell disease.

Sickle cell retinopathy in Jamaican children: a search for prognostic factors.

Children with homozygous sickle cell (SS) disease and with sickle cell-haemoglobin C (SC) disease, aged 6 1/2 to 8 1/2 years, were examined by fluorescein angiography/angioscopy to determine the presence of retinal nonperfusion. The haematological and clinical features of children with and without nonperfusion were compared. Retinal vessel closure was significantly correlated with low total haemoglobin, and high fetal haemoglobin, reticulocyte, and irreversibly sickled cell counts in SS disease, and with high reticulocyte count in SC disease. No relationships were apparent between vessel closure and other haematological indices or clinical events in either genotype.

Blood rheology and proliferative retinopathy in homozygous sickle cell disease.

Some haematological and rheological features were compared in 27 age and sex matched pairs of patients (15 male, 12 female) with homozygous sickle cell (SS) disease with and without proliferative sickle retinopathy (PSR). Significant haematological differences between the groups were a higher haemoglobin and a lower fetal haemoglobin in PSR positive males and a higher MCHC in PSR positive females. The plasma viscosity and characteristics of erythrocyte filterability did not differ between those with and those without PSR, although PSR positive males had a significantly higher whole blood viscosity when measured at high shear and at the patients own packed cell volume.

Haematological change in sickle cell–haemoglobin C disease and in sickle cell‐beta thalassaemia: a cohort study from birth

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell‐haemoglobin C (SC) disease, sickle cell‐β+ thalassaemia, and in sickle cell‐β° thalassaemia.

Alpha thalassaemia and the macular vasculature in homozygous sickle cell disease.

The interaction of homozygous alpha thalassaemia 2 with homozygous sickle cell (SS) disease results in a generally milder haematological picture with less intravascular sickling, less haemolysis, and higher haemoglobin levels. Clinically, patients are generally more mildly affected, though not all vaso-occlusive complications are reduced. Thus there is a possibility that the advantages gained by inhibition of sickling have been offset by the rheological disadvantages of the higher haemoglobin level. The capillary bed in the perimacular region of the posterior pole has been used to examine the degree of vaso-occlusion in age and sex matched controls with SS disease with and without homozygous alpha thalassaemia 2. The results demonstrated significantly less capillary abnormalities in the perimacular region of patients with alpha thalassaemia, though the size of the foveal avascular zone and the grading of perimacular capillary drop-out did not differ between the 2 genotypes. These results are compatible with a mild inhibitory effect of alpha thalassaemia on vaso-occlusion of the macular vasculature in SS disease.