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Background
This is a relatively common anemia which is inherited. The genetic abnormality controls the formation of hemoglobin, the complex molecule which carries oxygen in the red blood cell. If the defective gene is inherited, the red cells will contain this abnormal hemoglobin (HbS). The result are red cells, which are normally pliable and flexible spherules, becoming rigid and sickled in appearance. The result leads to stasis, clogging the blood flow through smaller vessels and potentially causing tissue death or an infarct. This can cause pain and a low blood count (anemia). If both doses of the defective gene are inherited, it is sickle cell disease. If only one dose of the gene is inherited, it is sickle cell trait.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE/
PREVALENCEMost common inherited disorder of red blood cells
72,000 Americans8% of the African American population are carriers
GEOGRAPHY 1 in 500 African Americans EPIDEMIOLOGIC ASSOCIATIONS MALARIA
Diagnostic criteria and risk factors for Plasmodium ovale malaria.Faye FB, Spiegel A, Tall A, Sokhna C, Fontenille D, Rogier C, Trape JF.
Unite de Recherche Paludologie-Afrotropicale, Institut de Recherche pour le Developpement, Dakar, Senegal.
J Infect Dis 2002 Sep 1;186(5):690-5 Abstract quote Plasmodium ovale is a common malaria parasite in Africa, but the epidemiology of P. ovale malaria is poorly known. Exposure to malaria, parasitemia, and morbidity were monitored for 6 years among the residents of a village in Senegal. The relationship between the level of P. ovale parasitemia and fever risk were analyzed, and diagnostic criteria for clinical P. ovale malaria were established.
Then the relationships between the occurrence of P. ovale clinical malaria and a series of entomological, epidemiological, and genetic factors were investigated. There was no increased risk of fever when the P. ovale parasite count was <800 parasites/microL of blood. Of 6621 episodes of illness, 114 (1.7%) were attributable to P. ovale.
Although most clinical episodes occurred during early childhood, a low incidence of the disease persisted among adults. Sickle cell trait carriers had increased susceptibility to the disease.
DISEASE ASSOCIATIONS CHARACTERIZATION HEREDITARY SPHEROCYTOSIS
Interaction of sickle cell trait with hereditary spherocytosis: splenic infarcts and sequestration.Ustun C, Kutlar F, Holley L, Seigler M, Burgess R, Kutlar A.
Department of Medicine, Section of Hematology/Oncology, Medical College of Georgia, Augusta, Ga. 30912, USA.
Acta Haematol 2003;109(1):46-9 Abstract quote The association of sickle cell trait (SCT) and hereditary spherocytosis (HS) has been reported in only 18 patients. Three of these 18 patients experienced splenic infarct or acute splenic sequestration.
We report here a 46-year-old African-American male, the oldest reported case to date, who experienced episodes of hemolysis and severe left upper quadrant pain for the past 26 years. The patient had compensated hemolysis with splenomegaly. A CT scan of the abdomen revealed a large infarct in the spleen. The diagnosis of SCT was confirmed with isoelectric focusing, cation exchange and reverse-phase HPLC. The presence of a silent, interacting globin variant as the cause of hemolysis and sickling in the spleen was ruled out by sequencing of the alpha1-, alpha2- and beta-globin genes.
The diagnosis of HS was established by an osmotic fragility test. The interaction of HS and SCT leads to RBC dehydration with increased MCHC and intracellular Hb S concentration presumably favoring intrasplenic sickling and resultant splenic infarcts and sequestration as seen in this case.
RENAL MEDULLARY CARCINOMA
Renal medullary carcinoma: a report of 2 cases and review of the literature.Dimashkieh H, Choe J, Mutema G.
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Arch Pathol Lab Med 2003 Mar;127(3):e135-8 Abstract quote Renal medullary carcinoma is a recently described aggressive neoplasm of the kidney. With the exception of 2 patients, all other reported cases have been associated with sickle cell hemoglobinopathies, mainly sickle cell trait and hemoglobin SC disease.
Renal medullary carcinoma is a highly malignant tumor with evidence of angiolymphatic and distant metastasis at the time of diagnosis. No specific genetic abnormality has been identified in this neoplasm despite its close association with a genetic disease.
We describe 2 cases of renal medullary carcinoma, one associated with hemoglobin SC disease, and the other with what we believe to be the first reported case associated with sickle cell disease.
PATHOGENESIS CHARACTERIZATION GENERAL Autosomal recessive disease
Point mutation in the hemoglobin beta gene (HBB) found on chromosome 11p15.4
Mutation in HBB results in the production of a structurally abnormal hemoglobin (Hb), called HbSLow oxygen levels or high hemoglobin concentrations, in individuals who are homozygous for HbS, the abnormal HbS clusters together, distorting the RBCs into sickled shapes
Deformed and rigid RBCs become trapped within small blood vessels and block them, producing pain and damaging organs
ARGININE METABOLISM
- Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease.
Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT.
Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, CA 94609, USA.
JAMA. 2005 Jul 6;294(1):81-90. Abstract quote
CONTEXT: Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability of l-arginine, the substrate for nitric oxide synthesis. We hypothesized that increased arginase activity and dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, and patient outcomes.
OBJECTIVE: To explore the role of arginase in sickle cell disease pathogenesis, pulmonary hypertension, and mortality.
DESIGN: Plasma amino acid levels, plasma and erythrocyte arginase activities, and pulmonary hypertension status as measured by Doppler echocardiogram were prospectively obtained in outpatients with sickle cell disease. Patients were followed up for survival up to 49 months.
SETTING: Urban tertiary care center and community clinics in the United States between February 2001 and March 2005.
PARTICIPANTS: Two hundred twenty-eight patients with sickle cell disease, aged 18 to 74 years, and 36 control participants.
MAIN OUTCOME MEASURES: Plasma amino acid levels, plasma and erythrocyte arginase activities, diagnosis of pulmonary hypertension, and mortality.
RESULTS: Plasma arginase activity was significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlated with the arginine-ornithine ratio, and lower ratios were associated with greater severity of pulmonary hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence interval [CI], 1.2-5.2; P = .006). Global arginine bioavailability, characterized by the ratio of arginine to ornithine plus citrulline, was also strongly associated with mortality (risk ratio, 3.6; 95% CI, 1.5-8.3; P<.001). Increased plasma arginase activity was correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels.
CONCLUSIONS: These data support a novel mechanism of disease in which hemolysis contributes to reduced nitric oxide bioavailability and endothelial dysfunction via release of erythrocyte arginase, which limits arginine bioavailability, and release of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine to ornithine and arginine to ornithine plus citrulline are independently associated with pulmonary hypertension and increased mortality in patients with sickle cell disease.ENDOTHELIAL CELL ADHESION MOLECULE
Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells.Brown MD, Wick TM, Eckman JR.
School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Pediatr Pathol Mol Med 2001 Jan-Feb;20(1):47-72 Abstract quote Microvascular complications in sickle cell disease occur as a result of obstruction of small vessels by deoxygenated sickle cells. Cerebrovascular complications are also common and result from obstruction of large blood vessels by thrombosis with changes in vessels that have some similarity to those found in arteriosclerotic vascular disease. Endothelial damage and activation from sickle cell-endothelial interactions may contribute to both. We find that endothelial cells have increased expression of VCAM-1, E-selectin, and ICAM-1 when exposed to sickle blood cells.
The concentration-dependent, sickle-induced, adhesion molecule expression is significantly greater than that promoted by normal cells. The time course of Cell Adhesion Molecule (CAM) expression is similar to that induced by TNF-alpha and IL1. Studies after white cell enrichment and reduction suggest leukocytes are the primary mediators. CAM expression by endothelial cells appears stimulated by soluble factors. Antibody inhibition studies support TNF-alpha and IL-1, produced by sickle leukocytes, as the primary soluble factors responsible for the observed CAM expression.
Both the induction of endothelial CAM expression and subsequent endothelial adherence of sickle erythrocytes may play significant roles in the pathophysiology of sickle-related complications, and reduction in CAM expression may provide a new approach to treatment.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION THROMBO-ELASTOGRAPH
- Thrombo-elastographic and hemostatic characteristics in pediatric patients with sickle cell disease.
Yee DL, Edwards RM, Mueller BU, Teruya J.
Department of Pediatrics, Cancer Center & Hematology Service, Baylor College of Medicine, Houston, Tex 77030, USA.
Arch Pathol Lab Med. 2005 Jun;129(6):760-5. Abstract quote
CONTEXT: Patients with sickle cell disease suffer from a variety of vaso-occlusive events that may be related to activation of the hemostatic system. Thromboelastography assesses the functionality of this system from a global standpoint and has demonstrated some utility in detecting hypercoagulable states in varied clinical settings, but it has not been systematically evaluated in patients with sickle cell disease.
OBJECTIVE: To characterize the findings of thromboelastography in patients with sickle cell disease during periods of steady state and illness, to compare these results with those of healthy controls, and to correlate these profiles with other measured hemostatic parameters.
DESIGN: In this cross-sectional study, we obtained thromboelastographic and other hemostatic data on specimens from 46 patients with sickle cell disease (35 with hemoglobin SS, 7 with hemoglobin SC, and 4 with hemoglobin S-beta thalassemia) and 20 healthy race-matched controls. Data were obtained from patients with sickle cell disease at baseline conditions (n = 41) and in the setting of acute illness (n = 5).
RESULTS: Patients with hemoglobin SS had lower reaction time and higher angle, maximum amplitude, and coagulation index values on thromboelastography than the control group. Hemoglobin SC patients had higher angle, maximum amplitude, and coagulation index values than controls. Hemoglobin S-beta thalassemia patients showed no significant differences compared with controls. Five hemoglobin SS patients with recent or current illness demonstrated increased maximum amplitude and coagulation index compared with hemoglobin SS patients at baseline conditions.
CONCLUSIONS: Patients with sickle cell disease demonstrated a significant hypercoagulable state in thromboelastography profiles, with the degree of abnormality dependent on the type of sickle cell disease and perhaps the presence of acute illness. Continued follow-up of this patient cohort, as well as further study of larger and more homogeneous patient groups, is required to adequately assess the utility of thromboelastography in predicting complications of sickle cell disease.URINE ALBUMIN
Accuracy of the urinary albumin to creatinine ratio as a predictor of albuminuria in adults with sickle cell disease.Lima CS, Bottini PV, Garlipp CR, Santos AO, Costa FF, Saad ST.
Haematology and Haemotherapy Centre, Faculty of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, Brazil.
J Clin Pathol 2002 Dec;55(12):973-5 Abstract quote AIM: To test the usefulness of a random urine specimen albumin to creatinine ratio (A/C) in predicting 12 hour urinary albumin excretion (12UA) in patients with sickle cell disease.
METHODS: 12UA and A/C were measured in nocturnal urine collections and random morning urine samples, respectively, of 72 patients with sickle cell disease.
RESULTS: The correlation of A/C values with 12UA values did not provide support for the use of random urine specimens for predicting urinary albumin excretion (UAE) in these patients. However, values of A/C >/= 0.45 and < 0.45 were indicative of raised and normal UAE, respectively. The sensitivity, specificity, and accuracy of the test were 100.0%, 87.2%, and 91.7%, respectively.
CONCLUSIONS: This method cannot be recommended for predicting 12UA in patients with sickle cell disease, but it is useful for selecting patients who should collect 12 hour urine for the estimation of UAE.
Risk factors for microalbuminuria in children with sickle cell anemia.McBurney PG, Hanevold CD, Hernandez CM, Waller JL, McKie KM.
Department of pediatrics, Medical College of Georgia, Ausgusta, Georgia 30912-3795, USA.
J Pediatr Hematol Oncol 2002 Aug-Sep;24(6):473-7 Abstract quote PURPOSE: To determine the prevalence of microalbuminuria and to establish clinical characteristics associated with microalbuminuria in children with sickle cell anemia.
PATIENTS AND METHODS: Urine samples of all children (homozygous SS) followed in the Medical College of Georgia's Children's Medical Center Sickle Cell Clinic were screened for microalbuminuria. Random samples were obtained from continent patients at routine office visits between September 1996 and November 1999. A retrospective chart survey was performed to determine clinical correlates for microalbuminuria. Medical records were reviewed for age, sex, hemoglobin, and episodes of pneumonia, pain, aplasia, acute chest syndrome, priapism, and avascular necrosis. Demographic and clinical variables were compared with microalbuminuria by univariate and multivariate logistic regression.
RESULTS: One hundred forty-two patients ages 21 months to 20 years made up the study group. The prevalence of microalbuminuria was 19%. Both increasing age and a lower hemoglobin level were found to correlate with microalbuminuria. By multivariate analysis, boys with microalbuminuria were likely to have a lower hemoglobin level and girls with microalbuminuria were likely to be older. None of the following factors were significantly related to microalbuminuria: pain, pneumonia, acute chest syndrome, priapism, avascular necrosis, or aplastic episodes.
CONCLUSIONS: Microalbuminuria is strongly and directly related to age and strongly and inversely related to hemoglobin levels. Identification of risk factors for microalbuminuria may allow earlier intervention to prevent renal complications in patients with sickle cell disease.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS CARDIAC
Myocardial infarction and transient ventricular dysfunction in an adolescent with sickle cell disease.Deymann AJ, Goertz KK.
Department of Pediatrics, Division of Pediatric Critical Care and Cardiology, University of Kansas Medical Center, Kansas City 66160, USA.
Pediatrics 2003 Feb;111(2):E183-7 Abstract quote We report a case of an adolescent who had sickle cell disease and previous evidence of myocardial damage and presented with abdominal pain and rapid progression to cardiogenic shock and subsequent development of myocardial infarction.
To our knowledge, this represents only the second report of a case of acute myocardial ischemia and subsequent infarction resulting transient ventricular dysfunction reported in a child with sickle cell disease successfully treated with exchange transfusion. The pathophysiology of this complication remains unclear, and cardiac complications may remain undetected as lung, bone, and brain infarcts are more common and the pain associated with sickle cell crisis may mask the ischemic symptoms.
Multiple factors may contribute to ischemia in addition to the presence of a vaso-occlusive crisis or infection. Acute or chronic myocardial ischemia are probably more prevalent than currently known.
DENTAL CARIES
Sickle cell anemia and dental caries: a literature review and pilot study.Laurence B, Reid BC, Katz RV.
Howard University College of Dentistry, Restorative Department, Washington, DC 20059, USA.
Spec Care Dentist 2002 Mar-Apr;22(2):70-4 Abstract quote The purpose of this cohort study was to determine whether individuals with sickle cell anemia (SCA) were more susceptible to dental caries than non-sickle-cell control subjects. A review of the literature suggests several reasons why individuals with SCA may be at increased risk.
Thirty-five cases of SCA aged 6 years and older were identified from a screening of 15,900 current patient files at the Howard University College of Dentistry Dental Clinic. A total of 140 non-SCA control subjects (four per case), frequency-matched on enrollment period (+/- 5 yrs) and age (+/- 2 yrs if under age 21, or +/- 5 yrs if 21 or over), was selected by a nonbiased method from the same dental clinic files. SCA cases and controls were identical on mean age (30.4 +/- 19 yrs, ranging from 5 to 92 yrs) and were similar in sex distribution (males: 34% of SCA cases, 40% of controls).
The mean number of permanent teeth present was very similar for SCA cases and controls (23.4 +/- 6.4 vs. 24.2 +/- 6.4). The mean DMFT was 21% higher in the SCA cases (12.0 +/- 8.4 vs. 9.9 +/- 6.9), and the mean DMFS was 26% higher in the SCA cases (33.0 +/- 32.3 vs. 26.2 +/- 27.7). While there was virtually no difference in DMFS between SCA cases and controls for 6- to 19-year-olds, for subjects aged 20 and older, the DMFS was 30.4% higher in the SCD cases. For all ages, the M component for SCA cases was 40.7% higher, and the D component was 20.0% higher, while the F component was only 3.5% higher than for controls. Untreated decay (the D/D+F surfaces ratio) was 24.4% higher in the SCA cases.
The findings from this pilot study suggest that SCA cases have a higher susceptibility to dental caries and/or that SCA patients may have different treatment pathways once caries is detected. While none of the observed differences was statistically significant, these findings were of clinical interest and should be pursued in future large-scale studies.
FETAL HYPOXIA
Maternal sickle cell trait and fetal hypoxia.Manzar S.
Department of Neonatology, King Faisal University & King Fahd University Hospital, Al-Khobar, Saudi Arabia.
Am J Perinatol 2000;17(7):367-70 Abstract quote Patients with sickle cell trait (SCT) usually run a benign course. But they may develop vaso-occlusive crisis, which may lead to hypoxia. During these episodes, pregnant women with SCT may effect the developing fetus. This report describes an interesting finding of subtle degree of fetal hypoxia associated with maternal SCT.
Twenty mothers with SCT were compared with 20 controls for the amount of circulating nucleated red blood cells (NRBC) and marker of fetal hypoxia at birth. Elevated number of circulating NRBC were noted in the cord blood of neonates born to mother with SCT as compared with controls, suggesting evidence of intrauterine fetal hypoxia.
A larger prospective study is needed to elaborate further on this association.
GALLBLADDER
The role of laparoscopic cholecystectomy in the management of acute cholecystitis in patients with sickle cell disease.Al-Mulhim AS, Al-Mulhim FM, Al-Suwaiygh AA.
Department of Surgery, King Fahad Hospital, Hofuf, Al Hassa, Saudi Arabia
Am J Surg 2002 Jun;183(6):668-72 Abstract quote BACKGROUND: As emergency surgery in sickle cell disease patients is associated with high morbidity, the aim of the study was to assess the safety of laparoscopic cholecystectomy in the acute state for these patients.
METHODS: Over a 5-year period, April 1994 till December 1998, 35 sickle cell patients with acute cholecystitis had laparoscopic cholecystectomy within the first 5 days of presentation. A retrospective study of these was undertaken.
RESULTS: Thirty-five patients were diagnosed as having acute cholecystitis with sickle cell disease. There were 26 female and 9 male patients; 5 patients needed preoperative and 1 patient needed postoperative endoscopic retrograde cholangiopancreatography. Twenty-seven patients needed simple transfusion and 8 needed partial exchange; conversion was necessary in two cases (5.7%). The mean hospital stay was 5.3 days and the complication rate was 17.5%.
CONCLUSIONS: Because of the lack of significant complications, we believe that laparoscopic cholecystectomy for acute cholecystitis is safe and recommended in experienced hands with adequate preoperative preparation for patients with sickle cell disease.
KIDNEY
Sickle cell nephropathy at end-stage renal disease in the United States: patient characteristics and survival.Abbott KC, Hypolite IO, Agodoa LY.
Nephrology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Clin Nephrol 2002 Jul;58(1):9-15 Abstract quote BACKGROUND: The patient characteristics, including age at presentation to end-stage renal disease (ESRD) and mortality associated with sickle cell nephropathy (SCN) have not been characterized for a national sample of patients.
METHODS: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of SCN.
RESULTS: Of the study population, 397 (0.11%) had SCN, of whom 93% were African-American. The mean age at presentation to ESRD was 40.68+/-14.00 years. SCN patients also had an independently increased risk of mortality (hazard ratio 1.52, 95% CI: 1.27-1.82) even after adjustment for placement on the renal transplant waiting list, diabetes, hematocrit, creatinine, and body mass index. However, when receipt of renal transplantation was also included in the model, SCN was no longer significant (p = 0.51, HR = 1.10, 95% CI: 0.82-1.48). SCN patients were much less likely to be placed on the renal transplant waiting list or receive renal transplants in comparison to age and race matched controls, and results of survival analysis were similar in this model.
CONCLUSIONS: SCN patients were much less likely to be listed for or receive renal transplantation than other comparable patients with ESRD. SCN patients were at independently increased of mortality compared with other patients with ESRD, including those with diabetes, but this increased risk did not persist when models adjusted for their low rates of renal transplantation.
OSTEONECROSIS
The natural history of symptomatic osteonecrosis in adults with sickle-cell disease.Hernigou P, Bachir D, Galacteros F.
Department of Orthopaedic Surgery and Traumatology, Hopital Henri Mondor, Creteil, France.
J Bone Joint Surg Am 2003 Mar;85-A(3):500-4 Abstract quote BACKGROUND: Adult patients with sickle-cell disease are at risk for the development of osteonecrosis of the hip. However, there is little information in the literature about the rate of progression of osteonecrosis once symptoms begin. The purpose of this study was to evaluate the natural history of the symptomatic hip in adult patients with osteonecrosis and sickle-cell disease.
METHODS: Ninety-two symptomatic hips in sixty-four consecutive adult patients with sickle-cell disease were initially evaluated between 1980 and 1987. Sixty symptomatic hips had radiographic evidence of osteonecrosis at the initial evaluation: forty-three were classified as stage II; two, as stage III; and fifteen, as stage IV, according to the system of Steinberg et al. The other thirty-two hips had lesions (stage I) that were evident only on magnetic resonance imaging. All patients were evaluated after a mean duration of follow-up of seventeen years.
RESULTS: Of the seventy-five hips without collapse of the femoral head at the initial evaluation, sixty-five demonstrated collapse within five years after the diagnosis. The average time between the diagnosis and collapse was forty-two months for stage-I hips and thirty months for stage-II hips. At the most recent follow-up examination, ninety hips had had collapse of the femoral head and eighty-eight of the ninety-two hips had had surgery because of intractable pain.
CONCLUSIONS: Symptomatic osteonecrosis of the hip in sickle-cell disease has a high likelihood of leading to femoral head collapse, necessitating surgical intervention. When osteonecrosis develops, the deterioration is rapid and, in most patients, operative intervention is necessary because of intractable pain.
LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.
PRIAPISM
Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study.Adeyoju AB, Olujohungbe AB, Morris J, Yardumian A, Bareford D, Akenova A, Akinyanju O, Cinkotai K, O'Reilly PH.
Department of Urology, Royal Bolton Hospital, Bolton, UK.
BJU Int 2002 Dec;90(9):898-902 Abstract quote OBJECTIVE: To define the incidence, risk factors and complications of priapism in a large population of patients with sickle-cell anaemia in five centres in the UK and Nigeria, as priapism is common among these patients, but the precise characteristics of the condition in this population are poorly documented.
PATIENTS AND METHODS: A questionnaire was developed and administered to patients with sickle-cell disease. Questions were designed to define the incidence, nature, precipitants, duration, treatment and complications of priapism. A distinction was made between acute (severe) priapism and the recurrent, 'stuttering' type.
RESULTS: The questionnaire was completed by 130 patients (mean age 25 years, sd 11, range 4-66) from the five centres; 102 (78%) were homozygous Hb SS genotype, 19 (15%) were Hb SC genotype and two (1.5%) were Hb Salpha-thalassaemia. Of the patients, 46 (35%) reported a history of priapism, and of these, 33 (72%) had a history of stuttering priapism, while 24 (52%) had had an acute episode of priapism. The mean age of onset of priapism was 15 years, with 75% of patients having the first episode before their 20th birthday. Sexual activity was the most frequent precipitating factor, with fever and/or dehydration being the next most common. Of the 46 patients, 10 (21%) with a history of priapism reported having erectile dysfunction. A similar proportion reported dissatisfaction with sexual intercourse, including a fear of engaging in sexual activity.
CONCLUSION: The incidence of priapism among patients with sickle-cell anaemia is high (35%). The implications of priapism for erectile and sexual function are significant and documented in this large series. The treatment of this condition in these patients remains unstandardised. This study highlights the need for an increased awareness of the problems associated with priapism among patients, families and medical professionals.
PULMONARY HYPERTENSION
Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival.Castro O, Hoque M, Brown BD.
Center for Sickle Cell Disease and Division of Cardiology, Department of Medicine, Howard University College of Medicine, Washington, DC 20059, USA
Blood 2003 Feb 15;101(4):1257-61 Abstract quote Few results on cardiac catheterization have been published for patients with sickle cell disease (SCD) with pulmonary hypertension (PHTN). Their survival once this complication develops is unknown.
We analyzed hemodynamic data in 34 adult patients with SCD at right-sided cardiac catheterization and determined the relationship of PHTN to patient survival. In 20 patients with PHTN the average systolic, diastolic, and mean pulmonary artery pressures were 54.3, 25.2, and 36.0 mm Hg, respectively. For 14 patients with SCD without PHTN these values were 30.3, 11.7, and 17.8 mm Hg, respectively. The mean pulmonary capillary wedge pressure in patients with PHTN was higher than that in patients without PHTN (16.0 versus 10.6 mm Hg; P =.0091) even though echocardiography showed normal left ventricular systolic function.
Cardiac output was high (8.6 L/min) for both groups of patients. The median postcatheterization follow-up was 23 months for patients with PHTN and 45 months for those without PHTN. Eleven patients (55%) with PHTN died compared to 3 (21%) patients without PHTN (chi(2) = 3.83; P =.0503). The mean pulmonary artery pressure had a significant inverse relationship with survival (Cox proportional hazards modeling). Each increase of 10 mm Hg in mean pulmonary artery pressure was associated with a 1.7-fold increase in the rate (hazards ratio) of death (95% CI = 1.1-2.7; P =.028). The median survival for patients with PHTN was 25.6 months, whereas for patients without PHTN the survival was still over 70% at the end of the 119-month observation period (P =.044, Breslow-Gehan log-rank test).
Our findings suggest that PHTN in patients with SCD shortened their survival.
STROKE
Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.Scothorn DJ, Price C, Schwartz D, Terrill C, Buchanan GR, Shurney W, Sarniak I, Fallon R, Chu JY, Pegelow CH, Wang W, Casella JF, Resar LS, Berman B, Adamkiewicz T, Hsu LL, Ohene-Frempong K, Smith-Whitley K, Mahoney D, Scott JP, Woods GM, Watanabe M, Debaun MR.
University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Pediatr 2002 Mar;140(3):348-54 Abstract quote OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD) who have an initial stroke temporally unrelated to another medical event are at higher risk for recurrent stroke than are children who had strokes temporally related to medical events.
METHODS: A retrospective cohort study of children with SCD and stroke who received regularly scheduled blood transfusions for a minimum of 5 years was conducted. Medical records were examined for the documentation of antecedent or concurrent medical events (hypertension, acute chest syndrome, aplastic crisis, fever associated with infection, exchange transfusion) associated with physician contact within 14 days before the initial stroke.
RESULTS: A total of 137 pediatric patients from 14 centers were studied. Mean age at first stroke was 6.3 years (1.4 to 14.0 years) with mean follow-up of 10.1 years (5 to 24 years). Thirty-one (22%) patients had a second stroke (2.2 per 100 patient years); 26 patients had an identified medical or concurrent event associated with their initial stroke. None of these patients had recurrent stroke 2 or more years after the initial event. The remaining 111 patients had an ongoing risk of recurrent stroke (1.9 per 100 patient-years) despite long-term transfusions (P =.038).
CONCLUSIONS: The absence of an antecedent or concurrent medical event associated with an initial stroke is a major risk factor for subsequent stroke while receiving regular transfusions.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL BONE MARROW Perivascular fibrosis in the bone marrow in sickle cell disease.
Manci EA, Culberson DE, Gardner JM, Brogdon BG, Shah AK, Holladay JE, Powell RW, Mankad VN.
Department of Pathology, University of South Alabama, Mobile 36604, USA.
Arch Pathol Lab Med. 2004 Jun;128(6):634-9. Abstract quote
CONTEXT: Magnetic resonance imaging of bone marrow in homozygous sickle cell disease (hemoglobin [Hb] SS) shows nonhomogeneous, mottled signals that increase with age and number of crises. The pattern of these signals is reminiscent of the underlying vascular architecture, but histopathology of this tissue has not been adequately studied.
OBJECTIVE: To elucidate the histopathology of blood vessels in the bone marrow in sickle cell disease.
DESIGN: Retrospective histochemical morphometric study of bone marrow arteries by point counting in HbSS (13 cases) and sickle cell Hb C (HbSC) (8 cases) compared to nonanemic normal controls (HbAA) (10 cases). All patients were nondiabetic, normotensive, younger than 37 years, and matched for age group.
RESULTS: The mean point count for perivascular fibrous tissue was significantly greater in the HbSS group (P <.001) in both small (P <.001) and medium-sized (P =.002) vessels, and in both age groups (pediatric, P <.001; adult, P =.005) compared with the HbAA group. Additional analysis showed the difference was significant in HbSS pediatric small vessels (P <.001) and in pediatric and adult medium vessels (P =.045 and P =.03, respectively). Ratios of fibrous tissue to muscle showed proportionately greater fibrous tissue in HbSS pediatric small (P <.001) and medium-sized vessels (P =.02), and in adult large vessels (P =.03). Mean point counts for muscle were significantly decreased in HbSS small vessels when all ages were compared as a group (P =.02), but when compared by age groups, counts were significantly increased in adult HbSS medium-sized vessels (P =.01). Overall mean point counts for muscle and fibrous tissue in the HbSC group were intermediate between those of the HbSS and HbAA groups, but were not significantly different from counts in the HbAA group (P =.78 and P =.35, respectively).
CONCLUSION: In sickle cell disease, arterial vessels in the bone marrow show significantly increased fibrous connective tissue and changes in muscle that vary with age and vessel size.LUNGS
Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases.Haque AK, Gokhale S, Rampy BA, Adegboyega P, Duarte A, Saldana MJ.
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77755, USA.
Hum Pathol 2002 Oct;33(10):1037-43 Abstract quote Pulmonary hypertension is one of the major causes of morbidity and mortality of patients with sickle cell hemoglobinopathy (SCH). Although a clinically recognized complication of sickle cell disease (SCD), there are few published pathologic studies of pulmonary findings in these patients.
The aim of this study was to define the pulmonary pathologic changes and to investigate correlation between the pathologic changes, the antemortem diagnosis of pulmonary hypertension, and the severity of SCH. Cases of SCH were identified from the autopsy database using Snomed codes. Clinical and echocardiograph data were collected for correlation with the pathologic data.
A total of 20 adult patients (12 males and 8 females) were identified. Hemoglobin electrophoresis results were available for 16 patients, with hemoglobin S fraction percentages ranging from 23% to 97.8%. Eleven patients had SCD, 5 patients had sickle cell trait (SCT), and the remaining 4 patients without hemoglobin electrophoresis were included in the SCT group. The mean age of the SCT group was higher than that of the SCD group (P = 0.03). Histologically, all 20 patients demonstrated changes in pulmonary vasculature considered diagnostic of pulmonary hypertension grade I to grade IV, associated with plexiform lesions in 60% of patients. Medial hypertrophy and intimal hyperplasia/fibrosis, considered potentially reversible lesions, were seen in all patients. A weak association was found between SCD and plexiform lesions. Fibroelastic degeneration of small arteries, arterioles, and venules was identified in almost all (95%) cases. Clinically, tricuspid regurgitation was detected by echocardiogram in 10 of 20 (50%) patients; 6 of these 10 had significant regurgitation to allow estimation of systolic pressure. Sudden death occurred in 8 patients, with males having a significantly higher incidence. Cardiomegaly was present in 95% of patients, however, autosplenectomy and hepatic cirrhosis/hemochromatosis were observed almost exclusively in patients with SCD. Cirrhosis was found to have a strong positive association with SCD.
This study demonstrates pulmonary hypertensive changes in all 20 autopsied patients who had SCH but died from various causes. We conclude that a high prevalence of pulmonary hypertension is associated with SCH with consequent high mortality. Therefore, patients with SCH would benefit from a regular periodic assessment for pulmonary hypertension regardless of age, sex, and severity of hemoglobinopathy.
PROGNOSIS CHARACTERIZATION HOSPITALIZATIONS
Frequent and prolonged hospitalizations: a risk factor for early mortality in sickle cell disease patients.Houston-Yu P, Rana SR, Beyer B, Castro O.
Department of Pediatrics and Child Health, Howard University, Washington, DC 20060, USA.
Am J Hematol 2003 Mar;72(3):201-3 Abstract quote A subset of patients with sickle cell disease (SCD) has frequent and prolonged hospitalizations. Clinical outcomes for this subset of patients are not known.
We analyzed mortality data in 71 such patients enrolled in a case management study. Adult patients (mean age 32 years) with SCD and > or = 50 hospitalization days/year or > or = 6 admissions/year were enrolled. Clinical and psychosocial data were obtained. During a mean 24-month follow up, 11 of 71 patients died (15.5%). Patients who died had a higher mean number of hospitalization days in the year before study entry (116 vs. 40, P < 0.000008) and were also more depressed than those who survived (mean score 17.8 vs. 11.9, P = 0.031).
Frequent and prolonged hospitalizations are a risk factor for early mortality in patients with SCD.
NEUROLOGIC
Sickle cell disease: the neurological complications.Prengler M, Pavlakis SG, Prohovnik I, Adams RJ.
Neurosciences Unit, Institute of Child Health, University College and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
Ann Neurol 2002 May;51(5):543-52 Abstract quote The genetic cause of sickle cell disease has been known for decades, yet the reasons for its clinical variability are not fully understood. The neurological complications result from one point mutation that causes vasculopathy of both large and small vessels.
Anemia and the resultant cerebral hyperemia produce conditions of hemodynamic insufficiency. Sickled cells adhere to the endothelium, contributing to a cascade of activated inflammatory cells and clotting factors, which result in a nidus for thrombus formation. Because the cerebrovascular reserve becomes exhausted, the capacity for compensatory cerebral mechanisms is severely limited.
There is evidence of small-vessel sludging, and a relative deficiency of nitric oxide in these vessels further reduces compensatory vasodilatation. Both clinical strokes and silent infarcts occur, affecting motor and cognitive function. New data suggest that, in addition to sickle cell disease, other factors, both environmental (eg, hypoxia and inflammation) and genetic (eg, mutations resulting in thrombogenesis), may contribute to a patient's stroke risk.
The stroke risk is polygenic, and sickle cell disease can be considered a model for all cerebrovascular disease. This complex disease underscores the potential intellectual and practical distance between the determination of molecular genetics and effective clinical application and therapeutics.
PSYCHIATRIC
A prospective study of the relationship over time of behavior problems, intellectual functioning, and family functioning in children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease.Thompson RJ Jr, Armstrong FD, Link CL, Pegelow CH, Moser F, Wang WC.
Duke University, 114 Allen Building, Box 90042, Durham, NC 27708-0042, USA.
J Pediatr Psychol 2003 Jan-Feb;28(1):59-65 Abstract quote OBJECTIVE: To longitudinally assess the relationship of behavioral problems, intellectual functioning, and family functioning in children with sickle cell disease (SCD).
METHOD: The study sample included 222 children enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD). The study protocol included intellectual evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. At least two complete sets of measures were obtained across four assessment points over the study period of 9 years.
RESULTS: Intellectual functioning declined, but family functioning and behavior problem scores did not change significantly. Consistent behavior problems were reported by mothers for 9% of the children. The risk of consistent behavior problems was not related to MRI classification, gender, education level of mother, or age of the child but significantly increased with higher baseline levels of family conflict and decreased with higher baseline full-scale IQ. An increase in behavior problems was associated with an increase in family conflict.
CONCLUSIONS: Maternal appraisal of family conflict is a risk factor for the small subgroup of children with SCD with consistent mother-reported behavior problems and a salient intervention target for fostering adaptation.
Cognitive functioning in children with sickle cell disease: a meta-analysis.Schatz J, Finke RL, Kellett JM, Kramer JH.
Department of Psychology, University of South Carolina, Columbia, USA.
J Pediatr Psychol 2002 Dec;27(8):739-48 Abstract quote OBJECTIVE: To establish whether sickle cell disease (SCD) affects cognitive functioning in children with no evidence of cerebral infarction.
METHODS: We conducted a meta-analysis of studies of cognition in SCD to determine the size of any statistical difference between children with SCD and controls. Methodological factors were evaluated according to the size and frequency of group differences.
RESULTS: There were small but reliable decrements in cognitive functioning on IQ measures (4.3-point difference overall). The most methodologically rigorous studies showed a highly similar pattern. Sampling issues associated with the effect size for IQ were identified. Measures of specific abilities appear more sensitive than IQ scores to cognitive decrements in SCD.
CONCLUSIONS: SCD is associated with cognitive effects even in the absence of cerebral infarction. The causes of this cognitive decrement may include direct effects of SCD on brain function or indirect effects of chronic illness.
UROLOGICAL COMPLICATIONS
Urologic manifestations of hematologic disease sickle cell, leukemia, and thromboembolic disease.Molitierno JA Jr, Carson CC 3rd.
Division of Urology, 428 Burnett Womack Building, CB7235, University of North Carolina Medical Center, Chapel Hill, NC 27599, USA.
Urol Clin North Am 2003 Feb;30(1):49-61 Abstract quote Advances in medicine are allowing patients with hematologic disease to live longer and healthier lives than ever before. As these patients age, however, manifestations of their disease processes may develop as complications in other organ systems.
We discussed the major genitourinary complications of sickle cell anemia, leukemia, and thromboembolic disease. These range from the benign inability to concentrate urine that is seen in sickle cell disease to renal infarction that results from nephrotic syndrome. Our ability to treat and prevent these complications will improve as our understanding of these disease processes and their pathophysiology grows. Additionally, it is important for urologists to understand the underlying pathophysiology of hematologic disease to best serve the patients. For example, it may be the urologist who makes the diagnosis of ovarian vein thrombosis in a pregnant woman with right lower quadrant pain and fever.
This diagnosis, with the proper treatment of antibiotics and anticoagulation, could prevent the potential development of septic thrombophlebitis. Urologists will increasingly be called upon to deal with the manifestations of these complex diseases as these patients are living longer. It is our duty to educate ourselves about these disease processes so that we can make the best clinical decisions for our patients.
TREATMENT CHARACTERIZATION GENERAL
Drugs for preventing red blood cell dehydration in people with sickle cell disease.Riddington C, De Franceschi L.
Institute of Child Health, University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, UK, L12 2AP.
Cochrane Database Syst Rev 2002;(4):CD003426 Abstract quote BACKGROUND: Sickle cell disease is an inherited disorder of haemoglobin, which results in abnormal red blood cells. These can deform and cause blockages in blood vessels, leading to acute crises such as pain, stroke and splenic sequestration, and chronic organ and tissue damage. Recently research has begun to focus on therapies which prevent the red blood cells deforming by reducing the loss of water and ions from the cells. However, little is known about the effectiveness and safety of such drugs.
OBJECTIVES: To assess the relative risks and benefits of drugs which aim to prevent sickle cell related crises by reducing red blood cell dehydration.
SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: December 2001.
SELECTION CRITERIA: All those randomised or quasi-randomised controlled trials of drugs which aim to prevent sickle cell crises by reducing red cell dehydration, compared to placebo or an alternative treatment.
DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials for inclusion, assessed trial quality and extracted data from the included studies.
MAIN RESULTS: Of the 27 trials identified, two met the inclusion criteria. The two trials tested the effectiveness of zinc sulphate and piracetam to prevent sickle cell related crises in a total of 246 patients. A reduction in pain crises was shown in the piracetam study over one year (weighted mean difference (WMD) -1.9 (95% CI -3.01, -0.79)), although blood counts were not significantly changed. The zinc trial showed a significant reduction in the total number of pain, haemolytic, aplastic and sequestration crises over one and a half years (WMD -2.83 (95% CI -3.51, -2.15)), but our analysis was limited by non-reporting of standard deviations for some data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in either trial.
REVIEWER'S CONCLUSIONS: While the results of both zinc and piracetam for reducing sickle related crises are encouraging, larger, and/or longer term multicentre trials over a number of years are needed to evaluate the effectiveness of these therapies for patients with sickle cell disease.
HYDROXYUREA
Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment.Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M.
Boston University School of Medicine, Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, Mass.
JAMA 2003 Apr 2;289(13):1645-51 Abstract quote CONTEXT: Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality.
OBJECTIVE: To determine whether hydroxyurea attenuates mortality in patients with SCA.
DESIGN: Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Follow-up, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period.
SETTING: Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada.
PATIENTS: Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients.
INTERVENTION: In the MSH, patients were randomly assigned to receive hydroxyurea (n = 152) or placebo (n = 147).
MAIN OUTCOME MEASURE: Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts. The randomized trial was not designed to detect specified differences in mortality.
RESULTS: Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250 000/mm3 and hemoglobin levels lower than 9 g/dL had increased mortality (P =.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/dL after the trial was completed compared with 15% when HbF levels were 0.5 g/dL or higher (P =.03 ). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P =.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P =.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P =.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal.
CONCLUSIONS: Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown.
NITRIC OXIDE
Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease.Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C.
Pediatric Emergency, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA.
JAMA 2003 Mar 5;289(9):1136-42 Abstract quote CONTEXT: Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion.
OBJECTIVE: To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients.
DESIGN: Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001.
SETTING: Urban, tertiary care children's hospital in the United States.
PARTICIPANTS: Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis.
INTERVENTION: Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours.
MAIN OUTCOME MEASURES: Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration.
RESULTS: Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed.
CONCLUSIONS: Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.
SPLENECTOMY
Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.Owusu-Ofori S, Riddington C.
Department of Medicine, Komfo Anokye Teaching Hospital, P.O.Box 1934 Ghana, Kumasi, Ghana.
Cochrane Database Syst Rev 2002;(4):CD003425 Abstract quote BACKGROUND: Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long term management used in different parts of the world.
OBJECTIVES: To assess whether splenectomy (total or partial) to prevent acute splenic sequestration crises in people with sickle cell disease improved survival and decreased morbidity in patients with sickle cell disease, as compared with regular blood transfusion.
SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and hand searching abstract books of conference proceedings Additional randomized controlled trials were sought from the reference lists of the studies found and reviews identified by the search strategy. Date of the most recent search: December 2001
SELECTION CRITERIA: All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises to no treatment or blood transfusion in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS: No trials of splenectomy for acute splenic sequestration were found.
MAIN RESULTS: No trials of splenectomy for acute splenic sequestration were found.
REVIEWER'S CONCLUSIONS: Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises but there is lack of evidence from trials that it improves survival and decreases morbidity in sickle cell disease. There is a need for a well-designed, adequately powered randomised controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes as a means of improving survival and decreasing mortality from ASS in people with sickle cell disease.
STEM CELL TRANSPLANTATION
Stem cell transplantation for sickle cell disease: can we reduce the toxicity?Fixler J, Vichinsky E, Walters MC.
Department of Hematology and Oncology, Program in Blood and Marrow Transplantation, Children's Hospital Oakland, 747 Fifty-Second Street, Oakland, CA 94609-1809, USA.
Pediatr Pathol Mol Med 2001 Jan-Feb;20(1):73-86 Abstract quote Since the genetic basis of sickle cell anemia was discovered over 50 years ago, many therapies have been developed for the treatment of this disorder.
Hematopoietic cell transplantation offers curative potential, but it is associated with a 5-10% risk of dying. Patients who undergo allografting but develop stable donor-host hematopoietic chimerism appear to experience a significant clinical benefit.
Our paper discusses the risks and benefits of hematopoietic cell transplantation in patients with sickle cell disease and summarizes the outcome of 147 patients who received allografts for sickle cell disease. We also review the development of new approaches to establish stable mixed chimerism after transplantation for sickle cell disease.
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