Showing papers on "Sickle cell anemia published in 1992"
TL;DR: Transcranial ultrasonography can identify the children with sickle cell disease who are at highest risk for cerebral infarction and periodic ultrasound examinations and the selective use of transfusion therapy could make the primary prevention of stroke an achievable goal.
Abstract: Background. Stroke, especially cerebral infarction, is a major cause of morbidity and mortality in children with sickle cell disease. Primary prevention of stroke by transfusion therapy may be feasible if there is a way to identify the patients at greatest risk. Transcranial Doppler ultrasonography can measure flow velocity in the large intracranial arteries. The narrowing of these arteries, which leads to cerebral infarction, is characterized by an increased velocity of flow. Methods. Using transcranial Doppler ultrasonography, we prospectively measured the velocity of cerebral blood flow in children and young adults being followed because of sickle cell disease. The results were classified as either normal or abnormal on the basis of the highest velocity of flow in the middle cerebral artery. Abnormal velocity was defined as a flow ≥170 cm per second, a definition determined by post hoc analysis to maximize the predictive success of the test. The end point was a clinically apparent first cerebr...
618 citations
TL;DR: Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin production in response to the drug, and no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.
396 citations
TL;DR: It is concluded that a high leukocyte count and an acute decrease of hemoglobin are risk factors for stroke in patients with homozygous sickle cell disease.
373 citations
TL;DR: Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin production in response to the drug, and no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.
340 citations
TL;DR: Evidence is offered that a target pretransfusion HbS level of 50% affords a continuing high rate of protection against recurrent cerebral infarction in sickle cell disease after 4 years of a conventional transfusion program.
159 citations
Journal Article•
TL;DR: It is concluded that plasma TNF is frequently elevated in subjects with sickle cell disease, and IL-1 is also elevated in some subjects, and a direct role for these cytokines in the pathogenesis of vascular occlusion in sicklecell disease was not demonstrated.
Abstract: To determine whether tumor necrosis factor (TNF) and interleukin-1 (IL-1) might be involved in the pathogenesis of sickle cell disease and its complications, TNF-alpha and IL-1-alpha were measured using enzyme-linked immunosorbent assay in 59 plasma samples from 34 adult subjects with Hb SS or Hb SC who did not have documented infections. Tumor necrosis factor was elevated on at least one occasion in 27 subjects, including 18 of 21 subjects in the steady state and 13 of 19 subjects during painful crisis. Interleukin-1 was elevated on at least one occasion in 6 subjects, including 3 subjects in the steady state and 3 subjects in crisis. All subjects with elevated IL-1 also had elevated TNF. Tumor necrosis factor and IL-1 were similarly elevated in the steady state and during painful crisis. No correlation was noted between TNF or IL-1 levels and the extent of activation of coagulation, as measured by plasma levels of the fibrin D-dimer fragment, the overall severity of vascular occlusive disease in each subject, or the presence of specific vascular occlusive complications. We conclude that plasma TNF is frequently elevated in subjects with sickle cell disease, and IL-1 is also elevated in some subjects. A direct role for these cytokines in the pathogenesis of vascular occlusion in sickle cell disease was not demonstrated, but an indirect role was not excluded.
149 citations
TL;DR: In this paper, the authors collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+)-thalassemia.
118 citations
TL;DR: The term "steady state" is a misnomer, being characterised by biochemical and rheological fluctuation consistent with minor episodes of microvascular occlusion that are insufficient to cause the overt tissue infarction of painful crisis.
Abstract: AIMS: To determine the clinical, haematological, biochemical and rheological changes that occur in the asymptomatic steady state of sickle cell anaemia. METHODS: Patient self-assessment visual analogue scores (for wellbeing and tiredness), the blood concentration of acute phase proteins (C-reactive protein, orosomucoid, and fibrinogen), and blood rheology (percentage of dense cells and the number of sickled cells that occluded pores 5 microns in diameter) were studied longitudinally on 10 occasions in each of 20 outpatients with sickle cell anaemia. RESULTS: Patients in the steady state showed fluctuation in visual analogue scores, in concentration of acute phase proteins, and in rheological parameters consistent with minor episodes of tissue injury. Significantly more variation in acute phase proteins occurred in the steady state of 14 of the 20 patients who developed one or more vaso-occlusive crises during the 16 month study period. Rheological fluctuation in the steady state simulated rheological change during crisis, namely a transient rise and then fall in the number of dense and poorly filterable cells. CONCLUSIONS: The term "steady state" is a misnomer, being characterised by biochemical and rheological fluctuation consistent with minor episodes of microvascular occlusion that are insufficient to cause the overt tissue infarction of painful crisis.
94 citations
TL;DR: A pain-control program modeled on regimens used to treat chronic cancer pain reduced hospital use by adult patients with sickle cell pain.
Abstract: ▪Objective:To assess the effect of a structured analgesic regimen on hospital use by patients with sickle cell disease. ▪Intervention:Intravenous and oral controlled-release morphine was u...
89 citations
TL;DR: HbF was significantly related to dactylitis, painful crises, acute chest syndrome, and acute splenic sequestration and the relationship suggested that a critically low HbF concentration increased the risk, little difference in risk occurring between the medium and high HfF groups.
Abstract: 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.
84 citations
TL;DR: Following the introduction of pneumococcal polyvalent vaccine in 1978, incidence of infection decreased in SS children greater than 2 years of age, and no modification of the risk of infection was observed in immunized children less than 2 children of age.
Abstract: Annual age-specific incidence rates of Streptococcus pneumoniae or Haemophilus influenzae bacterial septicemia in sickle cell anemia (SS) were determined for the years of 1957 through 1989. Forty-nine patients had 64 episodes of septicemia among a population of 786 SS patients observed for 8,138 person-years. Peak frequency of infection occurred between 1968-1971 and 1975-1981 with a conspicuous absence of episodes in 1972, 1973, 1982-1984, and 1986-1987, thus demonstrating cycles of high and low attack rates. The annual age-specific incidence rate of septicemia varied from 64.5 (1965) to 421.1 (1980) per 1,000 person-years for those under 2 years of age and never exceeded 10.2 per 1,000 in those over 4 years of age. Following the introduction of pneumococcal polyvalent vaccine in 1978, incidence of infection decreased in SS children greater than 2 years of age. No modification of the risk of infection was observed in immunized children less than 2 years of age.
During these three decades, there has been a ten-fold increase in the number of SS adults over 20 years of age. The relative risk of chronic sickle complications comparing the survivors of septicemia to the non-infected patients was: subsequent death 1.76, retinopathy 4.06, avascular necrosis 1.95, symptomatic cholelithiasis 1.33, stroke 1.30, and priapsim 1.26. These data suggest that prognosis for lifetime severe SS is initially manifested as an increased risk of septicemia during childhood.
TL;DR: Information indicates that vigorous pain-control methods are used at institutions having a special interest in providing medical care for children with sickle cell disease.
Abstract: A questionnaire was sent to principal investigators of NIH-sponsored clinical research in sickle cell disease. Twenty of 21 respondents indicated they used parenteral narcotic analgesics for pain episodes sufficiently severe to warrant hospitalization. Eleven used meperidine; seven, morphine; and one each, nalbuphine, hydromorphone, and acetaminophen with codeine. They gave the agents at frequent, regular intervals or by continuous infusion. A total of 41 of more than 3,500 patients required chronic transfusion for pain control. Complications included meperidine-associated convulsions reported by nine respondents and addiction by six. This information indicates that vigorous pain-control methods are used at institutions having a special interest in providing medical care for children with sickle cell disease.
TL;DR: Six boys with homozygous sickle cell disease are described, in whom acute, severe neurologic abnormalities developed 1 to 11 days after partial exchange transfusion was performed to treat priapism that was unresponsive to more conservative therapy.
TL;DR: Further studies are needed to explain the physical and biochemical differences seen in children with sickle cell anemia despite dietary intakes that appear to be adequate and similar to those of controls.
Abstract: The nutritional status and dietary intake of children with sickle cell anemia were examined to confirm the presence of deficiencies. Nine children with sickle cell anemia and 19 controls were assessed. Resting energy expenditure was measured with open circuit indirect calorimetry and body composition was estimated from skinfold measurements. Three-day food records were analyzed for protein, zinc, vitamin A, folic acid, and iron content. Serum vitamin A, red blood cell zinc, red blood cell folate, serum folate, serum ferritin, hematocrit, total urine nitrogen, and 24-h urine creatinine levels were measured. The children with sickle cell anemia were leaner, weighed less, and had lower red blood cell zinc levels, lower serum vitamin A levels, lower urine nitrogen levels, and greater resting energy expenditure than controls. Serum and red blood cell folate levels were within normal ranges and similar to controls. The serum ferritin level was higher than controls and higher than normal for age. Dietary intake of energy and protein was more than that of controls, and dietary intake of zinc, vitamin A, folic acid, and iron was similar to that of controls and adequate compared to the Recommended Dietary Allowances. Further studies are needed to explain the physical and biochemical differences seen in children with sickle cell anemia despite dietary intakes that appear to be adequate and similar to those of controls.
TL;DR: It is concluded that although long-term consequences of less aggressive transfusion therapy are unknown, the use of such a regimen may be reasonable, particularly in patients with significant transfusional hemochromatosis.
TL;DR: The results suggest that the sickle cell gene abnormality has an adverse effect on endocrine functions and follow-up and appropriate management of endocrine dysfunctions are advocated in such patients.
Abstract: In this study, 80 male and female sickle cell patients, aged 4-50 years, with mild (severity index, SI or = 6) forms of the disease were investigated). The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, cortisol, growth hormone (GH), free thyroxine (T4), and free triiodothyronine (T3) were determined. The results were evaluated and the mean +/- 2 SD values were compared with those obtained in age- and sex-matched normal controls. The findings indicated gonadal hypofunction in the sickle cell patients, but with varied deviations from the mean results. Patients with the severe form of the sickle cell disease showed more frequent abnormalities of LH, FSH, cortisol and testosterone in comparison with the patients with a mild disease. The LH, FSH, cortisol and testosterone levels were lower, while T3 and T4 did not show significant differences between patients and the controls. The results suggest that the sickle cell gene abnormality has an adverse effect on endocrine functions. Follow-up and appropriate management of endocrine dysfunctions are advocated in such patients.
Journal Article•
TL;DR: A hemoglobin based "blood substitute" developed at Texas Tech University and produced in Italy was used in nine children with sickle cell anemia admitted to the Centre de l'Anemie S. S. of Kinshasa, Zaire and in the patients with vaso-occlusive crises, pain was quickly relieved.
Abstract: A hemoglobin based "blood substitute" developed at Texas Tech University and produced in Italy was used in nine children with sickle cell anemia admitted to the Centre de l'Anemie S. S. of Kinshasa, Zaire. Five of the children presented an "aplastic crisis," for example, a sudden decrease in hemoglobin concentration associated with absence of reticulocytes in the peripheral blood, and four were admitted with unremitting severe pain because of a "vaso-occlusive crisis." The blood substitute contained 10 per cent hemoglobin and was infused in a volume corresponding to 25 per cent of blood volume (calculated for each child as equal to 7 per cent of body weight in kilograms). No adverse reaction was noted. To the contrary, all patients presented beneficial effects. In the patients with aplastic crisis, the hemoglobin solution stimulated the bone marrow to a significant erythropoietic effect, whereby the number of reticulocytes in the peripheral blood increased from zero to 47 +/- 7 per cent. In the patients with vaso-occlusive crises, pain was quickly relieved.
TL;DR: In view of the high prevalence of clinical cases of sickle cell anemia, hemoglobin-H-disease and glucose-6-phosphate dehydrogenase deficiency in the archipelago of the State of Bahrain, a cord blood screening study was undertaken over a 15 month period (October 1984 to December 1985) to determine the gene frequency of these diseases.
Abstract: In view of the high prevalence of clinical cases of sickle cell anemia, hemoglobin-H-disease and glucose-6-phosphate dehydrogenase deficiency in the archipelago of the State of Bahrain, a cord blood screening study was undertaken over a 15 month period (October 1984 to December 1985) to determine the gene frequency of these diseases All the state hospitals participated in this study and a total of 10,327 cord blood samples obtained from babies born to Bahraini parents were analyzed These presented over 80% of all neonates born in the country during the study period The phenotypes detected included: AF, AF-Barts, SFA and SFA-Barts Homozygous sickle cell disease was detected in 21%, and in 112%, the sickle cell trait was present The incidence of alpha-thalassemia gene based on elevated Bart's hemoglobin was 243% in these neonates The incidence of G6PD-deficiency was as high as 209% Availability of these statistics has enabled the authorities in the Ministry of Health in collaboration with the National Hereditary Anemia Society to plan a comprehensive health care program for patients with hereditary diseases and their families
TL;DR: Experience shows that HU can be used for the treatment of severe forms of SCD with no major side effects, provided that the doses are monitored and that laboratory investigations are regularly undertaken.
Abstract: In this study 21 adults with severe form of sickle cell disease (SCD; sickle cell anaemia, n = 15; Hb S/β°-thal, n = 6) were treated with hydroxyurea (HU) to assess the effectiveness of the drug in ma
TL;DR: Almost 70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection.
Abstract: • Objective. —To determine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in several years, (2) longitudinally, the immune response to B19 parvovirus infection, and (3) whether patients with sickle cell disease experience recurrent or chronic B19 parvovirus infection. Design. —Prospective evaluation of patients with sickle cell disease and TAC to find evidence of B19 parvovirus infection and, if present, to document the pattern of serologic response with time. Setting. —Large urban teaching hospital. Patients. —Patients younger than 18 years with sickle cell disease who were admitted to the hospital with a diagnosis of TAC or who developed TAC while in the hospital for other reasons. Follow-up serologic studies of B19 parvovirus infection were done in eight patients. Measurements/Main Results. —Serum was tested for B19 parvovirus DNA/viral particles and specific anti-B19 parvovirus IgM and IgG antibodies. B19 parvovirus DNA/viral particles were detected in 11 (21%) of 53 patients with TAC. Specific anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of the 53 patients. Overall, 36 (68%) of 53 patients with TAC had evidence of acute B19 parvovirus infection as shown by the detection of B19 DNA parvovirus and/or specific anti-B19 parvovirus IgM antibodies in acute-phase serum. Follow-up serologic studies in eight patients with acute infection revealed disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and persistence of anti-B19 parvovirus IgG antibodies for up to 3½ years after the diagnosis of acute B19 parvovirus infection. No patient had evidence of recurrent or chronic B19 parvovirus infection. Conclusions. —Approximately 70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection. Once detected, anti-B19 parvovirus IgG antibodies remain detectable for several years. There was no evidence of chronic or recurrent B19 parvovirus infection in patients with sickle cell disease. (AJDC. 1992;146:1328-1330)
TL;DR: It is concluded that, although R SCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.
Abstract: The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.
TL;DR: The clinical diversity of SCD in Saudi Arabia is heterogeneous clinically and haematologically, and the occurrence of hand and foot syndrome, vaso-occlusive crisis, and increased frequency of requirement of blood transfusion and hospitalization differentiated the clinical presentation in the patients from south-western province.
Abstract: Sickle cell disease (SCD) exhibits itself in a broad spectrum of clinical behaviour ranging from a mild disease to an incapacitating condition. In this study, we have attempted to investigate the clinical diversity of SCD in different regions of Saudi Arabia. The results of haematological parameters and clinical manifestations in 41 children with SCD from the eastern province where the disease is mild, were compared with results obtained in 51 children from the south-western province (SWP), where the disease has been shown to be more severe. The severity index (SI) of patients from the eastern province ranged from 2 to 11 with a mean of 4.5 and in patients from the south-western province, the SI ranged from 2 to 18 with a mean of 9.5. In addition, the occurrence of hand and foot syndrome, vaso-occlusive crisis, and increased frequency of requirement of blood transfusion and hospitalization differentiated the clinical presentation of SCD in the patients from south-western province from those in the eastern province. Red blood cell level, total haemoglobin and packed cell volume were lower in the SCD children from the south-western province. Haemoglobin A2 level was significantly higher, while haemoglobin F, packed cell volume (PCV), mean corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC) did not show any significant differences. HbF level did not influence the haematological parameters significantly in the SWP patients. It is concluded that the SCD in Saudi population is heterogeneous clinically and haematologically.
TL;DR: Red blood cells from 24 patients with sickle cell disease were more adherent to cultured endothelium pretreated with the inflammatory cytokine, tumour necrosis factor (TNF) than RBCs from 22 healthy subjects.
Abstract: Red blood cells (RBCs) from 24 patients with sickle cell disease were more adherent to cultured endothelium pretreated with the inflammatory cytokine, tumour necrosis factor (TNF) than RBCs from 22 healthy subjects. The enhanced sticking was apparent in RBC preparations from patients who were in crisis (mean 190% increase from controls) and out of crisis (mean 220% increase) and was not related to the number of circulating RBCs, reticulocytes, platelets, leucocytes or haemoglobin levels. When irreversibly sickled RBCs, enriched by centrifugation on density gradients, were added to TNF-treated endothelium they were found to be significantly more adherent (mean 411% increase; P<0·001) than the unfractionated RBCs from the same patients. There was no difference between the adherent properties of sickle RBCs and normal RBCs for untreated endothelium.
Contributing factors to the enhanced adhesion to TNF-treated endothelium may be the low surface change of sickle RBCs, and increased levels of fibrinogen and von Willebrand's factor (vWF) in the patients’plasma. By acting on vascular endothelium to increase its adhesiveness for sickled RBCs, it is concluded that inflammatory cytokines such as TNF may have a prominent role in mediating the events that lead to microvascular occlusions in sickle cell disease.
TL;DR: Routine screening for congenital anomalies by ultrasound, an emerging subdiscipline of obstetric ultrasound, and its relevance to routine obstetric scanning.
Abstract: 1 Campbell S, Pearce JMF. The prenatal diagnosis of foetal strictural anomalies by ultrasound. Clin Obstet Gynaecol 1983;10:475-506. 2 Campbell S. Smith P. Routine screening for congenital anomalies by ultrasound. In: Rodeck CH, Nicolaides K. Prenatal diagnosis. London: Royal College of Obstetricians and Gynaecologists; Chichester: Wiley, 1984:325-30. 3 McNay M. Clinical considerations in screening for foetal abnormalities. British Medical Soctesv Ultrasound Bulletin. 1991;No 63:23. 4 Chitty LS, Hunt GH, Moore J, Lobb MO. Effectiveness of routine ultrasonography in detecting fetal structural abnormalities in a low risk population. BAMJ7 1991;303:1165. 5 Royal College of Physicians. Report: prenatal diagnosis in genetic screening. London: RCP, 1989: 14-5. 6 Thomson P. Where risks exist expectant mothers want tests. The Times 1991 Dec 2:15. 7 Royal College of Obstetricians and Gynaecologists. Working party report on routine ultrasound examination in pregnancy. London: RCOG, 1984:10. 8 Hecher K, Henning K, Spernol R, Szalay S. Spontaneous remission of urinary tract obstruction and ascites in a foetus with posterior urethral salves. Ultrasound in Obstetrics and Gynaecology. 1991;1:426-43. 9 Benacerraf BR, Adzick NS. Foetal diaphragmatic hernia; ultrasound diagnosis and clinical outcome. AmJ Obstet Gynecol 1987;156:573-6. 10 Crawford DC, Chita SK, Allan LD. Prenatal diagnosis of congenital heart disease: factors affecting obstetric management and survival. AmJ7 Obstet Gvnecol 1988;159:352-6. 11 Hansman M. The foetus as a patient: the foetus as a person? Ultrasound in Obstetrics and Gynaecology 1991;1:305-6. 12 Chervenak FA, McLullogh LB. Ethics, an emerging subdiscipline of obstetric ultrasound, and its relevance to routine obstetric scanning. Ultrasound in Obstetrics and Gynaecologv 1991;1: 18-20.
TL;DR: This study confirms that hydroxyurea therapy increases Hb F production and provides objective evidence of a significant reduction in hemolytic rate and intracellular polymerization and indicates that large-scale, controlled clinical trials are warranted to study the safety and efficacy of hydroxyUREa in the treatment of sickle cell disease.
TL;DR: Patients with sickle cell disease are more susceptible to osteomyelitis and septic arthritis than the population at large, and the knee was the joint most often involved in patients admitted to the authors' hospital from April 1988 to March 1991.
Abstract: Patients with sickle cell disease are more susceptible to osteomyelitis and septic arthritis than the population at large. Seventy eight patients with these conditions were admitted to our hospital from April 1988 to March 1991. Thirty had sickle cell disease, 14 had the sickle cell trait and 34 had normal electrophoresis. The tibia, followed by the femur and humerus were the bones most commonly affected, and the knee was the joint most often involved. Salmonella was the commonest organism in osteomyelitis and septic arthritis in sickle cell disease, whereas staphylococcus was commonest in normal patients and those with the sickle cell trait. Antibiotics that cover these two organisms must be considered in patients with sickle cell disease who are suspected of having osteomyelitis or septic arthritis.
TL;DR: In this article, recombinant human erythropoietin (rHuEpo) was administered to three transfusion-dependent patients with ESRD and homozygous sickle-cell disease (initial dose 100 U/kg twice weekly, increasing to 125 U/ kg at 6 weeks, and to 150 U /kg at 9 weeks in two patients).
Abstract: The development of end-stage renal disease (ESRD) in patients with sickle-cell anaemia results in increased transfusion dependence, increasing the risk of iron overload. Correction of anaemia with recombinant human erythropoietin (rHuEpo) in dialysis patients might also result in stimulation of haemoglobin F production, which protects against sickling, although very high doses were required to achieve this effect in non-uraemic animals. rHuEpo was administered to three transfusion-dependent patients with ESRD and homozygous sickle-cell disease (initial dose 100 U/kg twice weekly, increasing to 125 U/kg at 6 weeks, and to 150 U/kg at 9 weeks in two patients). This resulted in reticulocytosis and increased circulating erythroid blast-forming units. Total haemoglobin was predominantly HbA (i.e. transfused blood) at the start of the study, reflecting transfusion dependence, but after 3 months' treatment was between 60 and 94% HbS. No sickling crises occurred. Haemoglobin F remained at less than 3% of total haemoglobin. One patient was withdrawn at 10 weeks with CAPD peritonitis. The other two patients completed 12 weeks' treatment without transfusion but final Hb concentrations were 4.5 and 5.5 g/dl. Whether larger doses of rHuEpo will be more successful in managing such patients remains unclear. No effect on HbF production can be expected.
TL;DR: It is concluded that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.
Abstract: Five children with sickle cell anaemia underwent bone marrow transplantation (BMT) for severe clinical disease. The conditioning regimen for BMT was in busulfan plus cyclophosphamide. The allograft contained more than 5 x 10(8) nucleated cells per kg recipient. Prophylaxis of GVHD consisted of methotrexate and cyclosporin A. Therapy was well tolerated. Duration of neutropenia (less than 0.5 x 10(9)/l) was short (14-25 d). Platelet recovery (greater than 50 x 10(9)/l) occurred between day 12 and 45. The patients have been followed up for 8-28 months. No major infections occurred and long-term BMT-related toxicity was limited to mild, chronic GVHD in one patient. Mean haemoglobin levels remained above 10 g/dl. Haemoglobin electrophoresis showed AS patterns in all grafted patients--all marrow donors having sickle cell trait. From our preliminary data, we conclude that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.
Journal Article•
TL;DR: Admission and bed rest were the best determinants of complete healing of the chronic ulcers.
Abstract: Twenty five (17 male, 8 Female) sickle cell disease patients with 30 leg ulcers were studied over a 3 year period (January 1985 to December 1987) to provide information on the pathogenesis, course and management. There were 23 patients with homozygous sickle cell and 2 patients with sickle cell haemoglobin C disease. The mean age was 28 years (range 15-44 years). An antecedent history of trauma was obtained in 40% of the patients and 96% had a previous history of leg ulcer. The major site affected (93%) was the skin around the malleoli. In 68% of the patients a single organism was isolated and the commonest bacteria were Pseudomonas species, Staphylococcus aureus, Proteus species and B haemolytic streptococci. The major complications encountered were equinovarus deformity (36%) and chronic periosteitis (32%). The main topical antimicrobial used was Eusol either alone (52%) or in combination with Metronidazole (32%) or honey (12%). Complete healing occurred in 40% of patients, partial healing with deterioration in 16% and no significant change in 44%. Admission and bed rest were the best determinants of complete healing of the chronic ulcers.
TL;DR: A serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS, and this potentially life‐threatening complication should be considered in this condition.
Abstract: Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11-year span, while the other had two episodes of this complication during a 4-year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life-threatening complication should be considered in this condition.