RESUMEN
BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.
Asunto(s)
Anemia de Células Falciformes , Hematología , Accidente Cerebrovascular , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/tratamiento farmacológico , Niño , Hemoglobina Falciforme , Humanos , Hidroxiurea/uso terapéutico , Estados UnidosAsunto(s)
Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Isoanticuerpos/sangre , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Autoanticuerpos/sangre , Donantes de Sangre , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/inmunología , Incompatibilidad de Grupos Sanguíneos/etiología , Incompatibilidad de Grupos Sanguíneos/prevención & control , California , Niño , Transfusión de Eritrocitos/efectos adversos , Hospitales , Humanos , Grupos Minoritarios , Desarrollo de ProgramaRESUMEN
Hemoglobin Constant Spring (HbCS) is the most common nondeletional alpha-thalassemia variant causing HbH disease, making its detection crucial in populations at risk. Universal newborn screening for HbH is carried out in California. Identification of alpha-thalassemia genotypes responsible for HbH and HbH-CS requires rapid, accurate and cost-effective genotyping methods suitable for population screening. We incorporated the HbCS mutation into our existing seven-plex genotyping assay for common alpha-thalassemia deletions. To assess the feasibility and diagnostic utility of this expanded multiplex gap-PCR assay, we determined genotypic frequencies of HbCS in samples referred for alpha-thalassemia testing between 1 January 2006 and 31 December 2008. During the 3-year study period, 1436 samples were genotyped for alpha-thalassemia. HbH-CS accounted for 23 (13%) of the 176 cases of HbH disease identified. In a subset of 145 newborns referred by the California NBS program with an elevated Hb Bart's level at birth, HbH disease was confirmed in 134 (93%) and HbH-CS identified in 13 (10%) of these. This expanded genotyping assay has proven to be a rapid, reliable and clinically useful diagnostic tool for the detection of HbH-CS disease.
Asunto(s)
Hemoglobinas Anormales/genética , Reacción en Cadena de la Polimerasa/métodos , Eliminación de Secuencia/genética , Talasemia alfa/genética , California , Estudios de Seguimiento , Genotipo , Humanos , Recién Nacido , Talasemia alfa/sangre , Talasemia alfa/diagnósticoRESUMEN
Certain beta globin gene mutations produce a thalassemia major phenotype in the heterozygous state. While most such patients have thalassemia intermedia, we describe a young Guatemalan child with a de novo mutation in the beta globin gene, codon 31 T --> G (Hemoglobin Hakkari), who developed severe anemia at the age of 10 months and remains transfusion-dependent. The substitution of B13 leucine with arginine in the beta globin results in alteration of a critical heme contact point resulting in an extremely unstable variant hemoglobin and a clinical picture that is characterized by ineffective erythropoiesis and numerous intracytoplasmic inclusions within the erythrocyte precursors of the bone marrow. .
Asunto(s)
Hemoglobinas Anormales/genética , Mutación Puntual , Globinas beta/genética , Talasemia beta/genética , Guatemala , Humanos , Cuerpos de Inclusión , Lactante , Masculino , Talasemia beta/patologíaRESUMEN
AIM: To investigate the application of an expanded Transactional Stress and Coping Model for the psychological adjustment of non-chronically ill, African-American siblings of children with sickle cell disease (SCD). METHODS: Ninety-seven siblings (M = 11.24 years) from 65 families who care for a child with SCD participated. Primary caregivers completed the Coping Health Inventory for Parents, the Family Relations Scale and the Child Behaviour Checklist, while siblings completed the Kidcope, the Children's Self-Efficacy for Peer Interaction Scale, and the Social Support Scale for Children. RESULTS: Family processes were predictive of sibling adjustment, revealing that family coping, expressiveness and support improved adjustment, while family conflict predicted poor adjustment. CONCLUSION: Findings suggest that family-centered interventions stressing family expressiveness and support, while minimizing conflict, will contribute to sibling psychological adjustment.
Asunto(s)
Adaptación Psicológica , Anemia de Células Falciformes/psicología , Negro o Afroamericano/psicología , Hermanos/psicología , Estrés Psicológico/psicología , Adolescente , Negro o Afroamericano/genética , Anemia de Células Falciformes/genética , California/etnología , Niño , Evaluación de la Discapacidad , Familia/psicología , Femenino , Humanos , Masculino , Modelos Teóricos , Autoeficacia , Apoyo Social , Estadística como Asunto , Factores de TiempoRESUMEN
Pulmonary hypertension is common in adults with thalassaemia and other haemolytic anaemias. It was hypothesised that regular transfusions in thalassaemia major should both decrease the chronic haemolytic rate and be protective from pulmonary hypertension (PHT). To reduce the contribution of existing cardiac disease to PHT, the subjects were limited to patients with normal left ventricular shortening fractions. Associations with multiple laboratory markers of haemolysis, serum ferritin levels, chest X-rays findings and splenectomy status were also considered. We found no biochemical, transfusional, or clinical (except gender) differences in transfused thalassaemia patients with or without pulmonary hyper tension.
Asunto(s)
Hipertensión Pulmonar/etiología , Función Ventricular Izquierda , Talasemia beta/complicaciones , Adolescente , Adulto , Transfusión Sanguínea , Femenino , Ferritinas/sangre , Hemoglobinas/metabolismo , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Masculino , Talasemia beta/sangre , Talasemia beta/fisiopatología , Talasemia beta/terapiaRESUMEN
Historically, fractures are cited as a frequent problem in patients with Thalassemia prior to optimization of transfusion and chelation regimens. The aim of this study was to determine the prevalence of fractures in a contemporary sample of North American patients with Thalassemia. The North American Thalassemia Clinical Research Network (TCRN) database registry was used to gather historical data on 702 patients with common alpha and beta-Thalassemia diagnoses including Thalassemia Major (TM), Intermedia (TI), E/Beta, homozygous alpha Thalassemia (AT), Hemoglobin H disease (HbH) and HbH with Constant Spring (HbH/CS), who consented to a medical record chart review. Bone mineral density (BMD) measurements by DXA were available for review in a subgroup of patients (n = 312). The overall fracture prevalence among all Thalassemia syndromes was 12.1%, equally distributed between females (11.5%) and males (12.7%). Fractures occurred more frequently in TM (16.6%) and TI (12.2%) compared to E/Beta (7.4%) and alpha (2.3%). Prevalence increased with age (2.5% ages 0-10 years, 7.4% ages 11-19 years, 23.2% ages >20 years) and with use of sex hormone replacement therapy (SHRT) (P < 0.01). On average, BMD Z and T scores were 0.85 SD lower among patients with a history of fractures (mean Z/T score -2.78 vs. -1.93, 95% CI for the difference -0.49 to -1.22 SD, P = 0.02). Presence of other endocrinopathies (i.e. hypothyroidism, hypoparathyroidism and diabetes mellitus), anthropometric parameters, heart disease or hepatitis C were not significant independent predictors of fractures. These data indicate that fractures remain a frequent complication among the aging patients with both TM and TI beta-Thalassemia. However, the fracture prevalence has improved compared to published reports from the 1960s to 1970s. In addition, children with Thalassemia appear to have low fracture rates compared to the general population.
Asunto(s)
Fracturas Óseas/epidemiología , Talasemia/complicaciones , Adolescente , Adulto , Densidad Ósea , Niño , Preescolar , Femenino , Fracturas Óseas/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , América del Norte/epidemiología , PrevalenciaRESUMEN
Liver iron measurements using biosusceptometers have been validated on two low-TC SQUID (Superconducting Quantum Interference Device) systems (New York and Hamburg) built in the 1980's. Recently, two new instruments have been installed in Torino, Italy (2001), and Oakland, California (2003). The design of the Oakland system is similar to those in Hamburg and Torino. Improvements were made to adjust for significant environmental noise, moreover, an active electronic noise cancellation, a computer controlled water coupling reference system using a pressure feedback and a faster data acquisition system using software lockin amplifiers have been implemented. All 3 systems (Hamburg, Torino, Oakland) are using the same standardized operational protocol. Presented herein are the data collected from 276 patients measured with the SQUID biosusceptometer at Oakland since installation. The results from 149 patients with beta-thalassemia (beta-Thal, age: 2-66 y), 76 patients with sickle-cell disease (SCD, age: 5-55 y), 35 patients with various rare diseases (RD, age: 2-80 y), and 16 patients with hereditary hemochromatosis (HHC, age: 6-74 y) are reported. The liver iron concentration in the different groups are 222 - 7570 (beta-Thal), 518 - 7918 (SCD), 511 - 6234 (RD), 258 - 2041 (HHC) microg/g-liver (in vivo wet weight). The long-term reproducibility (12 months) in a patient on constant treatment regimen demonstrated a mean liver iron of 1141 +/- 133 microg/g-liver. The new SQUID Ferritometer located on the US West coast will give more patients access to this non-invasive liver iron assessment.
Asunto(s)
Magnetismo/instrumentación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia/diagnóstico , Anemia/fisiopatología , California , Niño , Preescolar , Campos Electromagnéticos , Femenino , Humanos , Hierro/análisis , Hierro/fisiología , Hígado/química , Hígado/fisiología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Arterias Cerebrales/fisiopatología , Infarto Cerebral/etiología , Anemia de Células Falciformes/terapia , Velocidad del Flujo Sanguíneo , Transfusión Sanguínea , Infarto Cerebral/epidemiología , Infarto Cerebral/fisiopatología , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Medición de Riesgo , Ultrasonografía Doppler TranscranealRESUMEN
Newborn screening is an accepted public health measure to ensure that appropriate health care is provided in a timely manner to infants with hereditary/metabolic disorders. Alpha-thalassemia is a common hemoglobin (Hb) disorder, and causes Hb H (beta4) disease, and usually fatal homozygous alpha(0)-thalassemia, also known as Hb Bart's (gamma4) hydrops fetalis syndrome. In 1996, the State of California began to investigate the feasibility of universal newborn screening for Hb H disease. Initial screening was done on blood samples obtained by heel pricks from newborns, and stored as dried blood spots on filter paper. Hb Bart's levels were measured as fast-moving Hb by automated high-performance liquid chromatography (HPLC) identical to that currently used in newborn screening for sickle cell disease. Subsequent confirmation of Hb H disease was done by DNA-based diagnostics for alpha-globin genotyping. A criterion of 25% or more Hb Bart's as determined by HPLC detects most, if not all cases of Hb H disease, and few cases of alpha-thalassemia trait. From January, 1998, through June, 2000, 89 newborns were found to have Hb H disease. The overall prevalence for Hb H disease among all newborns in California is approximately 1 per 15,000. Implementation of this program to existing newborn hemoglobinopathy screening in populations with significant proportions of southeast Asians is recommended. The correct diagnosis would allow affected infants to be properly cared for, and would also raise awareness for the prevention of homozygous alpha(0)-thalassemia or Hb Bart's hydrops fetalis syndrome.
Asunto(s)
Pruebas Genéticas , Hemoglobina H/análisis , Hemoglobinas Anormales/análisis , Tamizaje Neonatal , Talasemia alfa/epidemiología , Asia Sudoriental/etnología , Asiático , California , Cromatografía Líquida de Alta Presión , Femenino , Frecuencia de los Genes , Genotipo , Globinas/deficiencia , Globinas/genética , Hemoglobina H/genética , Hemoglobinas Anormales/genética , Humanos , Hidropesía Fetal/genética , Hidropesía Fetal/prevención & control , Recién Nacido , Masculino , Mutación Missense , Prevalencia , Eliminación de Secuencia , Talasemia alfa/diagnóstico , Talasemia alfa/etnología , Talasemia alfa/genéticaRESUMEN
BACKGROUND: Most sickle cell anemia patients undergo transfusion therapy to prevent complications. The Stroke Prevention Trial in Sickle Cell Anemia showed that transfusion therapy is effective in the primary prevention of stroke. Despite its efficacy, transfusion therapy is limited by alloimmunization. The purpose of this study was to determine if a multicenter trial could implement a transfusion program utilizing phenotypically matched blood to reduce alloimmunization. STUDY DESIGN AND METHODS: One hundred thirty children underwent RBC phenotyping and antibody screening with review of blood bank records. The protocol required use of WBC-reduced RBCs, which were matched for E, C, and Kell. Monthly alloantibody testing and review of transfusion forms were performed to determine compliance and the occurrence of any adverse events. RESULTS: Patient RBCs expressed a low frequency of Kell (2%), E (20%), and C (25%) antigens. Sixty-one patients received 1830 units. Ninety-seven percent of all units were WBC reduced. Only 29 units were inadvertently not matched for E, C, and Kell. Five patients (8%) developed a clinically significant alloantibody. Four developed a single antibody to E or Kell. Three patients (5%) developed a warm autoantibody. There were 11 transfusion reactions and 8 transfusion-associated events. Transfusion reactions included 6 febrile reactions (0.33%/unit), 3 allergic (0.16%/unit), and 2 hemolytic (0.11%/unit). Associated events included 4 episodes of hypertension (0.22%/unit), 3 crises (0.16%/unit), and 1 transient ischemic attack (0.05%/unit). CONCLUSION: This is the first multicenter study to show that extended RBC phenotyping can be implemented nationwide. Compared to studies, the alloimmunization rate dropped from 3 percent to 0.5 percent per unit, and hemolytic transfusion reactions dropped by 90 percent. It is recommended that all transfused sickle cell anemia patients be antigen matched for E, C, and Kell. Patients should be closely monitored during transfusions to avoid preventable risks.
Asunto(s)
Anemia de Células Falciformes/terapia , Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión Sanguínea , Eritrocitos/fisiología , Accidente Cerebrovascular/prevención & control , Adolescente , Anemia de Células Falciformes/inmunología , Autoanticuerpos/análisis , Niño , Preescolar , Femenino , Humanos , Isoanticuerpos/análisis , Masculino , Fenotipo , Estudios Prospectivos , Reacción a la TransfusiónRESUMEN
We describe a novel multilocus genotyping assay permitting simultaneous identification of 60 candidate markers for stroke in sickle cell anaemia (SCA). Based on cerebral magnetic resonance imaging (MRI), 69 patients were divided into stroke and control groups. The variant allele, CBS 278thr, showed protection from stroke, whereas the apoE3 allele showed a trend towards association with increased stroke risk. Several other variant alleles [TNFalpha (-308)A, CETP (-628)A, apoCIII (-641)A] showed a trend towards significant associations with stroke risk. These preliminary results on a small group of patients suggest that a multilocus genotyping assay may be valuable in identifying genes that increase the risk of stroke in SCA.
Asunto(s)
Anemia de Células Falciformes/genética , Cistationina betasintasa/genética , Accidente Cerebrovascular/genética , Adolescente , Alelos , Anemia de Células Falciformes/complicaciones , Apolipoproteínas E/genética , Estudios de Casos y Controles , Niño , Marcadores Genéticos , Genotipo , Humanos , Oportunidad Relativa , Reacción en Cadena de la Polimerasa/métodos , Accidente Cerebrovascular/etiología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVE: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke. METHODS: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain MRI at age 6 years or older, and (3) had no overt stroke before a first MRI. MRI results and clinical and laboratory parameters were tested as predictors of stroke. RESULTS: Among 248 eligible patients, mean age at first MRI was 8.3 +/- 1.9 years, and mean follow-up after baseline MRI was 5.2 +/- 2.2 years. Five (8.1%) of 62 patients with silent infarct had strokes compared with 1 (0.5%) of 186 patients without prior silent infarct; incidence per 100 patient-years of follow-up was increased 14-fold (1.45 per 100 patient-years vs 0.11 per 100 patient-years, P =.006). Of several clinical and laboratory parameters examined, silent infarct was the strongest independent predictor of stroke (hazard ratio = 7.2, P =.027). CONCLUSIONS: Silent infarct identified at age 6 years or older is associated with increased stroke risk.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Infarto del Miocardio/complicaciones , Accidente Cerebrovascular/etiología , Niño , Humanos , Lactante , Imagen por Resonancia Magnética , Infarto del Miocardio/diagnóstico , Factores de RiesgoRESUMEN
OBJECTIVES: To compare the results of serial neuropsychologic testing in children with sickle cell disease with the results of serial magnetic resonance imaging (MRI) examinations, particularly to evaluate neuropsychologic function in the absence of overt stroke. STUDY DESIGN: In the Cooperative Study of Sickle Cell Disease, serial neuropsychologic and MRI tests were performed in 373 patients (255 with hemoglobin SS and 118 with hemoglobin SC), 6 to 18 years of age. MRI of the brain and a neuropsychologic battery that included the Wechsler Intelligence Scale for Children (WISC-R or WISC-III) and the Woodcock-Johnson Math and Reading Achievement Tests were performed concurrently and repeated every 2 to 3 years. A silent infarct was defined as an MRI finding of increased signal intensity on T(2) imaging in a patient without a history of stroke. RESULTS: Twenty-seven patients, all with hemoglobin SS, had overt strokes and 62 had silent infarcts (52 with hemoglobin SS). Patients with hemoglobin SS and silent infarcts had significantly lower scores for math and reading achievement, Full-Scale IQ, Verbal IQ, and Performance IQ, when compared with those with normal MRI findings. In children with hemoglobin SS and normal MRI findings, the scores for Verbal IQ, math achievement, and coding (a subscale of Performance IQ) declined with increasing age. CONCLUSIONS: School-aged children with sickle cell disease had compromised neuropsychologic function in the presence of silent infarcts. In addition, they had declines in performance in certain areas of function over time. Therapeutic interventions that prevent or lessen cognitive impairment are needed before school entry for children with sickle cell disease.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Infarto del Miocardio/complicaciones , Pruebas Neuropsicológicas , Escalas de Wechsler , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Accidente Cerebrovascular/complicacionesRESUMEN
The Stroke Prevention Trial has confirmed that utilization of transcranial Doppler ultrasonography (TCD), which examines blood flow in large intracranial vessels, can identify children with sickle cell disease (SCD) who are at high risk of developing a premature stroke. It is not known to what extent the vasculopathy in SCD involves small vessels and whether the abnormalities, if present, correlate with large-vessel vasculopathy. Eighteen children with SCD were examined with TCD to determine middle cerebral artery (MCA) velocity and computer-assisted intravital microscopy (CAIM) to determine bulbar conjunctival vessel velocity during the same visit for vasculopathy correlation. High MCA velocity (> or = 200 cm/sec) was found by TCD in 4 patients who also showed abnormal conjunctival velocity (< 0.2 mm/sec or intermittent trickle flow) by CAIM. Three patients had conditional (> or = 170 cm/sec and < 200 cm/sec) MCA velocity: 2 showed abnormal (trickle) and 1 showed normal conjunctival velocity (1.9 mm/sec). One patient with unmeasurable MCA velocity had abnormal (trickle) conjunctival velocity. Of the remaining 10 patients who had normal MCA velocity, 2 showed abnormal (0.05 mm/sec and 0.1 mm/sec) and 8 showed normal conjunctival velocities (1.1-2.4 mm/sec). The MCA velocities correlated significantly with bulbar conjunctival flow velocities (P < or =.008, Fisher exact test). A correlation exists between MCA (large-vessel) and conjunctival (small-vessel) flow velocities. CAIM is a noninvasive quantitative technique that might contribute to the identification of SCD patients at high risk of stroke. Small-vessel vasculopathy might be an important pathological indicator and should be further explored in a large-scale study. (Blood. 2001;97:3401-3404)
Asunto(s)
Anemia de Células Falciformes/fisiopatología , Conjuntiva/irrigación sanguínea , Microcirculación/fisiopatología , Microscopía/métodos , Arteria Cerebral Media/fisiopatología , Ultrasonografía Doppler , Adolescente , Anemia de Células Falciformes/complicaciones , Velocidad del Flujo Sanguíneo , Niño , Preescolar , Humanos , Procesamiento de Imagen Asistido por Computador , Factores de Riesgo , Accidente Cerebrovascular/etiología , Grabación de Cinta de VideoRESUMEN
With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion-acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion-related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.
Asunto(s)
Anemia de Células Falciformes/terapia , Transfusión Sanguínea/normas , Anemia de Células Falciformes/complicaciones , Eliminación de Componentes Sanguíneos , Antígenos de Grupos Sanguíneos , Transfusión Sanguínea/métodos , Humanos , LeucocitosRESUMEN
A multicenter investigation of allogeneic bone marrow transplantation for children with sickle cell disease was conducted that included 27 European and North American transplant centers. Fifty-nine patients who ranged in age from 3.3 to 15.9 years (median, 10.1 years) received HLA-identical sibling marrow allografts between September 1991 and April 2000. Fifty-five patients survive, and 50 survive free from sickle cell disease, with a median follow-up of 42.2 months (range, 11.8 to 115 months) after transplantation. Of the 50 patients with successful allografts, 13 developed stable mixed donor-host hematopoietic chimerism. The level of donor chimerism, measured > or =6 months after transplantation in peripheral blood, varied between 90% and 99% in 8 patients. Five additional patients had a lower proportion of donor cells (range, 11% to 74%). Among these 5 patients, hemoglobin levels varied between 11.2 and 14.2 g/dL (median, 11.3 g/dL; mean, 12.0 g/dL). In patients who had donors with a normal hemoglobin genotype (Hb), the Hb S fractions were 0%, 0%, and 7%, corresponding to donor chimerism levels of 67%, 74%, and 11%, respectively. Among patients who had donors with sickle trait, the Hb S fractions were 36% and 37%, corresponding to donor chimerism levels of 25% and 60%, respectively. Thus, allograft recipients with stable mixed chimerism had Rb S levels similar to donor levels, and only 1 patient required a red blood cell transfusion beyond 90 days posttransplantation. None of the patients have experienced painful events or other clinical complications related to sickle cell disease after transplantation. These observations strongly suggest that patients with sickle cell disease who develop persistent mixed hematopoietic chimerism after transplantation experience a significant ameliorative effect.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Médula Ósea , Trasplante de Médula Ósea/métodos , Hematopoyesis , Quimera por Trasplante , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Hemoglobina Falciforme/análisis , Hemoglobinas/análisis , Humanos , Masculino , Estudios Prospectivos , Donantes de Tejidos , Trasplante Isogénico , Resultado del TratamientoAsunto(s)
Anemia de Células Falciformes/terapia , Transfusión Sanguínea , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/mortalidad , Bacteriemia/transmisión , Antígenos de Grupos Sanguíneos/inmunología , Sustitutos Sanguíneos/uso terapéutico , Terapia por Quelación , Niño , Preescolar , Transfusión de Eritrocitos/efectos adversos , Femenino , Infecciones por VIH/transmisión , Trasplante de Células Madre Hematopoyéticas , Hemosiderosis/tratamiento farmacológico , Hemosiderosis/etiología , Humanos , Hidroxiurea/uso terapéutico , Inmunización , Lactante , Recién Nacido , Esperanza de Vida , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Tamizaje Neonatal , Embarazo , Complicaciones Hematológicas del Embarazo/terapia , Reacción a la Transfusión , Viremia/transmisiónRESUMEN
Although the endocrine pancreas appears to play an important role in the pathophysiology of sickle cell disease, very little is known about the morphologic changes in this tissue. Our study was initiated to delineate the microscopic features of the endocrine pancreas in a large autopsy series of sickle cell hemoglobinopathies. From more than 650 cases archived at the Centralized Pathology Unit for Sickle Cell Disease (Mobile, AL), 224 autopsy cases were identified for review of clinical and gross autopsy findings and/or for microscopic studies, including histochemical stains (trichrome, reticulin, iron), and immunohistochemical stains (insulin, glucagon, somatostatin, and pancreatic polypeptide). The gross examinations were recorded as unremarkable in 65% of the autopsies. In childhood and adolescence (< or = 18 years), pancreas weights (50.76 +/- 5.16SE gm) were significantly greater (p < 0.0001) than age-matched controls (30.42 +/- 3.59SE gm). In adulthood, pancreas weights (108.34 +/- 5.29SE gm) were not significantly different from controls (110 gm). Microscopic findings included vascular congestion (48%), edema (65%), siderosis (31%), and nesidioblastosis (76%), which included islet cell dispersion (53%), hyperplasia (23%), and hypertrophy (25%). Analysis by age groups suggested that islet cell dispersion/hyperplasia persists unchanged, whereas diameters of compact islets tend to increase with age. These findings may be related to local tissue hypoxia and/or increased metabolic energy needs in sickle cell disease.