Graham R Serjeant

Central Retinal Artery Occlusion without Retrobulbar Hemorrhage after Retrobulbar Anesthesia

Four patients had central retinal artery occlusions after retrobulbar anesthesia with lidocaine HCl was administered before photocoagulation. One of these four had two separate episodes of closure. Only one had permanent visual loss, and none had evidence of retrobulbar hemorrhage. Each patient had a severe hematologic or vascular disorder. We think that direct trauma to the central retinal artery behind the globe, the pharmacologic or compressive effects of the injected solution, or both caused the occlusions in these patients.

Fetal haemoglobin and early manifestations of homozygous sickle cell disease.

The relevance of fetal haemoglobin (HbF) concentration to the development of early clinical manifestations of homozygous sickle (SS) disease has been investigated by examining the time to first occurrence and the proportional hazard of these complications in three groups of the HbF distribution at age 5 years. HbF was significantly related to dactylitis, painful crises, acute chest syndrome, and acute splenic sequestration. The relationship suggested that a critically low HbF concentration increased the risk, little difference in risk occurring between the medium and high HbF groups. The abdominal painful crisis and hypersplenism were not related to HbF concentration suggesting that the degree of sickling may not be important in their genesis. Parental education on acute splenic sequestration should be focused on children with HbF concentrations in the lowest part of the HbF distribution for age.

Height and weight reference curves for homozygous sickle cell disease

OBJECTIVE To derive height and weight growth reference curves for children with homozygous sickle cell disease. STUDY DESIGN Subjects (n = 315) were participants in a population based, longitudinal cohort study of sickle cell disease in Kingston, Jamaica. Regular measurements of height and weight were made from enrollment into the study at birth up to 22 years of age. RESULTS Sex specific growth reference curves for height for age and weight for age covering the age range 0–18 years are presented. CONCLUSION These growth reference curves are suitable for identifying coincidental growth problems in children with homozygous sickle cell disease.

Venous incompetence, poverty and lactate dehydrogenase in Jamaica are important predictors of leg ulceration in sickle cell anaemia

Clinical features and potential risk factors for chronic leg ulceration (duration >6 months) in homozygous sickle cell (SS) disease were examined in 225 subjects in the Jamaican Cohort Study. Potential risk factors included the number of HBA genes, steady state haematology, serum lactate dehydrogenase (LDH), venous incompetence, and socio‐economic status. Chronic ulcers occurred in 53 subjects with the highest risk of ulcer development at 18 years. The prevalence was 29·5% and cumulative incidence 16·7%. Gender or α‐thalassaemia trait did not affect the incidence of leg ulcer. Ulceration was associated with lower haemoglobin, red cell count, fetal haemoglobin, and socio‐economic status and higher reticulocyte count, platelet count, serum LDH and venous incompetence in univariate analyses. Venous incompetence [Hazard Ratio (HR) 3·0–4·0] and socio‐economic status (HR 0·8) were most consistently associated with leg ulceration on multivariate analysis. Regression models incorporating serum LDH suggested this to be a stronger predictor than haematological indices. The prevalence of ulcers at 30% is less than previous estimates in Jamaica, probably reflecting the lack of ascertainment bias in the Cohort Study, and also a real secular decline. In Jamaica, venous incompetence, low socio‐economic status, and high serum LDH were the strongest predictors of chronic ulceration.

A Randomized Clinical Trial of Feeder Vessel Photocoagulation of Proliferative Sickle Cell Retinopathy: I. Preliminary Results

A randomized prospective clinical trial of feeder vessel photocoagulation for proliferative sickle cell retinopathy was performed. In Chicago there were 34 argon laser-treated eyes and 30 control eyes. In Kingston there were 53 xenon arc treated eyes and 50 control eyes. Prolonged loss of visual acuity was rare in both photocoagulated and control eyes. Argon laser and xenon arc feeder vessel photocoagulation reduced the incidence of vitreous hemorrhage and visual loss from vitreous hemorrhage. However, photocoagulation was associated with an increased risk of choroidal neovascularization (xenon arc greater than argon laser) and retinal detachment (argon laser), although visual loss from these complications has not been seen in these patients so far.

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.

Hb S-β-Thalassemia: Molecular, Hematological and Clinical Comparisons

Clinical and hematological features are presented for 261 patients with identified β-thalassemia (β-thal) mutations. Mutations causing Hb S [β6(A3)Glu→Val]-β0-thal were IVS-II-849 (A>G) in 44%, frameshift codon (FSC) 6 (–A) in 14%, Hb Monroe [β30(B12)Arg→Thr] in 14%, and IVS-II-1 (G>A) in 10%. Mutations causing Hb S-β+-thal with 14-25% Hb A (type III) were –29 (A>G) mutation in 60%, –88 (C>T) in 22% and the polyadenylation signal site (polyA) (T>C) mutation in 14%, and in Hb S-β+-thal with 1-7% Hb A (type I), all had the IVS-I-5 (G>C) mutation. Hematologically, only minor differences occurred between the four Hb S-β0-thal mutations, but among the three mutations causing Hb S-β+-thal type III, levels of Hb A2, Hb F, hemoglobin (Hb), MCV and MCH were highest in the –88 and lowest in the polyA mutations. Clinically, Hb S-β0-thal and Hb S-β+-thal type I were generally severe, and Hb S-β+-thal type III disease with the –88 mutation was milder than that caused by the polyA mutation.

Haematological risk factors for pregnancy outcome in Jamaican women with homozygous sickle cell disease

Objective To examine the association between fetal outcome and the steady state haematology of mothers with homozygous sickle cell disease.

Iris atrophy in sickle cell disease.

Iris atrophy, of unknown origin and believed to be secondary to the vaso-occlusive process of sickle cell disease, has been observed in 25 eyes of 22 patients (two SS disease, 20 SC disease). The crude prevalence was highest in males with SC disease, in whom 14.7% of patients were affected. Iris atrophy was closely associated with proliferative sickle retinopathy in the same eye. Analysis of haematological indices failed to reveal any significant differences between patients with and without iris atrophy. The characteristics and distribution of iris atrophy are described as well as the histopathology in one 68-year-old male patient with SS disease.

Comparison of responses evoked by mild indirect cooling and by sound in the forearm vasculature in patients with homozygous sickle cell disease and in normal subjects

In normal individuals, novel or noxious stimuli commonly evoke the pattern of the alerting or defence response which includes cutaneous vasoconstriction, but vasodilatation in forearm skeletal muscle. We have compared cardiovascular responses evoked by sound and by indirect cooling in 60 patients with homozygous sickle cell (SS) disease and in 30 control subjects with normal haemoglobin genotype (AA). A sound of 90 dB, 1 kHz for 30 s evoked an increase in hand and forearm cutaneous vascular resistance (HCVR and FCVR) in SS patients and an increase in HCVR in AA subjects, as assessed from Doppler flowmetry. Meanwhile, a decrease in forearm vascular resistance (FVR) assessed by venous occlusion plethysmography, occurred in 14 out of 30 AA subjects and 25 out of 60 SS patients, indicating vasodilatation in forearm muscle; an increase in FVR occurred in the remainder. The proportions of SS patients and AA subjects who showed anincrease in FVR (53% vs 57%) were not significantly different. Cooling increased HCVR and FCVR in SS patients and increased FCVR in AA subjects; a decrease in FVR indicating vasodilatation, occurred in 12 out of 30 AA subjects, but in only 10 out of 60 SS patients. The proportion of SS patients who showed anincrease in FVR to cooling was greater than in AA subjects (83% vs 60%,P<0.05). Thus, SS patients are just as capable of showing the muscle vasodilatation of the alerting response to sound as AA subjects. That few SS patients showed muscle vasodilatation in response to cooling is consistent with the view that reflex vasoconstrictor responses to cooling are particularly strong in SS patients. This, in turn, is consistent with our hypothesis that the reflex vasoconstrictor response to cooling acts as a trigger for the painful crisis of SS disease by diverting blood flow away from active bone marrow.