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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary microvascular occlusion by abnormally adherent and/or nondeformable sickle red blood cells (SS cells) may contribute to the pathogenesis of acute chest syndrome of sickle cell disease. We hypothesized that regional alveolar hypoxia reduces SS cell deformability and, by causing regional vasoconstriction, slows regional perfusion, facilitating endothelial adhesion and mechanical entrapment of cells. In isolated rat lungs perfused at constant average flow with physiological salt solution, we separately ventilated the two lungs: one with 95% O2 and the other with 0, 2.5, 5, or 21% O2. We infused a bolus of 99mTc-labeled SS cells or normal human AA cells along with 113Sn-labeled 15-mu m microspheres as a perfusion marker, then sliced the lungs and counted 99mTc and 113Sn. Weight-normalized perfusion decreased with hypoxia (P < 0.02). Retention of AA cells (perfusion-normalized) averaged approximately 1% in lungs ventilated with 95% O2 and increased only twofold with 0% O2. In contrast, retention of SS cells averaged 3-fold higher than that of AA cells at 95 and 5% O2, 15-fold higher at 2.5% O2, and 25-fold higher at 0% O2 (P < 0.01). Histological examination demonstrated entrapment of individual SS cells in alveolar capillaries of hypoxic but not well-oxygenated lungs. Relief of hypoxia, but not increased perfusate flow, caused prompt efflux of most entrapped cells, which were primarily high-density (high mean corpuscular hemoglobin concentration) cells. Thus substantial retention of SS cells does not occur without hypoxia, but regional hypoxia and/or the resulting vasoconstriction causes extraordinary regional retention of dense SS cells, a phenomenon that appears to be due more to mechanical entrapment of nondeformable cells in capillaries than to endothelial adhesion.
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PMID:Pulmonary entrapment of sickle cells: the role of regional alveolar hypoxia. 892 95

Transfusion therapy is frequently used in the treatment of sickle cell disease and its complications, but its efficacy has not been well proven. Red cell transfusions are well established for the acute treatment of cerebrovascular accidents and for the prevention of their recurrence. Acute chest syndrome with respiratory insufficiency is also an established indication for transfusion, especially in children. The use of red cell transfusions, especially chronic transfusions, in the treatment of sickle cell disease should be initiated only after serious consideration of the clinical setting and possible adverse effects. Both risks and benefits should be discussed with the patient, and that discussion should be documented.
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PMID:Treating anemia. 895 18

Acute chest syndrome (ACS) is an important cause of morbidity and mortality in sickle cell disease (SCD). Previous studies reported conflicting pictures of ACS making therapeutic interventions difficult. The Cooperative Study of Sickle Cell Disease prospectively followed 3,751 patients enrolled from birth to 66 years of age for ACS. Data on presenting signs and symptoms, laboratory findings, and hospital course were collected. There were 1,722 ACS episodes in 939 patients. Young children (age 2 to 4 years) presented with fever and cough, a negative physical exam, and rarely had pain. Adults were often afebrile and complained of shortness of breath, chills, and severe pain. Upper lobe disease was more common in children; multilobe and lower lobe disease affected adults more often. Severe hypoxia occurred in 18% of adults tested and could not be predicted by examination or laboratory findings. Bacteremia was documented in 3.5% of episodes, but was strongly influenced by age (14% of infants and 1.8% of patients > 10 years). ACS was most common in winter with children having the most striking increase. Transfusion was used less frequently, but earlier in children. Young children were hospitalized for 5.4 days versus 9 days for adults. Fifty percent of adults had a pain event in the 2 weeks preceding ACS and children were more likely to have febrile events. The death rate was four times higher in adults than in children. Fatal cases generally developed rapid pulmonary failure and one third were associated with bacteremia. Age has a striking effect on the clinical picture of ACS. In children, ACS was milder and more likely due to infection, whereas in adults ACS was severe, associated with pain and had a higher mortality rate.
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PMID:Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease. 905 64

Sickle cell disease is characterized by recurrent episodes of acute pain. Some patients also suffer from chronic pain syndromes including avascular necrosis, leg ulcers, and intractable pain. Approaches to rational therapy of sickle pain include pharmacologic, nonpharmacologic, and preventive therapeutic interventions. Pharmacologic treatment of sickle pain entails the use of nonopioid analgesics, opioid analgesics, and adjuvants singly or in combination depending on the severity of pain. Meticulous evaluation and assessment of painful episodes should precede and accompany all approaches to management. The choice of the opioid analgesic, its route of administration, dose, and frequency of administration should be individualized on a case-by-case basis. Meperidine should be avoided whenever possible. Nonsteroidal anti-inflammatory drugs, meperidine, and morphine are contraindicated in the presence of renal failure. Administration of opioids on a fixed schedule or by patient-controlled analgesia is ideal for effective therapy. Nonpharmacologic approaches to manage sickle pain are underutilized and more studies are needed to determine their role in sickle pain. Preventive therapy of sickle pain is best achieved with hydroxyurea, which was found to decrease the frequency of crises significantly, decrease the incidence of acute chest syndrome, and decrease the need for blood transfusion.
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PMID:Management of sickle pain. 910 26

Oxygen saturation was determined by pulse oximetry in a representative sample of Jamaican patients with steady-state sickle cell disease in a cohort study from birth. There were 220 with homozygous sickle cell (SS) disease and 142 with sickle cell-haemoglobin C (SC) disease aged 9-18 years, and 122 with a normal haemoglobin (AA) genotype aged 15-18 years. Pulse oximetry (SpO2) values were lower in SS disease (mean [95% confidence interval], 92.5 [92.0-93.0]) than in SC disease (96.7[96.5-96.9]) or AA controls (97.1 [96.8-97.3]). Inhalation of 100% oxygen in SS patients with O2 saturations below 90% consistently increased saturation to 99-100%. In SS disease, SpO2 correlated positively with haemoglobin and fetal haemoglobin and negatively with reticulocyte counts but not with MCHC, MCV or bilirubin level. Mean SpO2 in SS subjects with a normal alpha globin gene complement (mean [SD], 91.7 [3.9]%) was lower than in heterozygotes (93.4 [4.0]%) or homozygotes (96.1 [3.0]%) for alpha+ thalassaemia, the effects of alpha-thalassaemia not being explained by differences in haemoglobin or MCHC. In SS disease, SpO2 levels were not associated with age (within this age range), sex, number of sick clinic visits or number of hospital admissions. Higher SpO2 levels were associated with greater height and weight, more frequent painful crises and less frequent acute chest syndrome, but these associations were not significant after adjustment for haemoglobin level. Desaturation is common in steady-state SS disease and knowledge of the individual's steady-state value may be important in the interpreting low values during acute complications.
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PMID:Pulse oximetry in a cohort study of sickle cell disease. 914 42

The acute chest syndrome of sickle cell disease is believed to be primarily a microvascular event. It will rarely involve the larger pulmonary vasculature. We present a case of sickle cell disease where segmental pulmonary arteries were temporarily occluded during the episode of sickling.
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PMID:Scintigraphic evidence of pulmonary vascular occlusion in sickle cell disease. 922 10

Hydroxyurea (HU) is the first drug that, under well-organized clinical trials, has shown the potential for altering significantly the clinical severity of sickle cell disease (SCD). The placebo-controlled trial of HU in adult SS hemoglobinopathy patients (the Multicenter Study of Hydroxyurea in Sickle Cell Anemia) reported in May 1995 that HU therapy reduced significantly the frequencies of severe pain episodes, acute chest syndrome, and transfusion. Despite these impressive results, no guidelines have been developed to direct clinicians on the use of HU in adult SCD patients. Small-scale phase II studies in children have reported increases in fetal hemoglobin (HbF) and F-cell levels in response to HU therapy. A larger phase II study, the Pediatric Hydroxyurea Study Group (HUG-KIDS), is under way and is expected to be completed by March 1998. The need for a large-scale placebo-controlled trial in children will be doubtful if no unusual short-term toxicity is demonstrated by HUG-KIDS. Guidelines regarding patient selection, dosing schedules, treatment goals, and short- and long-term monitoring parameters need to be established. The case is made of the organization of a clinical network to register and follow SCD patients treated with HU for long-term toxicity.
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PMID:Use of hydroxyurea in children with sickle cell disease: what comes next? 931 99

Hydroxyurea (HU) is the first widely used treatment to have an impact on the severity of disease in adult patients with sickle cell anemia, but limited data are available for younger patients or those with variant genotypes. We reviewed 324 months of experience with HU in 16 patients from 5.3 to 18.4 years of age treated for 6 to 50 months. The major toxicity was reversible neutropenia. Linear growth continued unchanged, and all patients gained weight. Hematologic results were similar to those reported in adults with increases in mean corpuscular volume (MCV) and total and fetal hemoglobin (HbF). We noted that the maximal hematologic effects occurred at less than the maximum dose. Clinically, patients experienced an 80% reduction in episodes of acute chest syndrome and a reduced need for blood transfusion, as well as a 30% decrease in the number of hospitalizations for painful events during HU therapy compared with an equivalent number of months before HU. These highly statistically significant results confirmed the value of HU in ameliorating the severe clinical course of pediatric patients. Similar effects were observed in three patients with sickle beta degrees-thalassemia, sickle beta+-thalassemia, and S-O Arab. Recurrent acute splenic sequestration and progressive symptomatic osteonecrosis were observed during HU. Thus, HU may not prevent the development of complications once organ damage is present. The challenge remains to determine when and to which pediatric patients with sickle cell disease HU should be offered.
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PMID:Hydroxyurea therapy for diverse pediatric populations with sickle cell disease. 931

We performed pulmonary function testing in 20 infants (11 male and 9 female; ages 3-30 months) with sickle cell disease to assess whether abnormal lung function develops early in life. Respiratory system compliance (Crs) and resistance (Rrs) were measured by the passive occlusion technique, functional residual capacity (FRC) was measured by the nitrogen washout technique, and tidal flow-volume loops and partial expiratory flow-volume curves were obtained by the thoracoabdominal compression technique to detect airway obstruction. Patients with Hb SS (Group I, n = 12) had significantly lower hemoglobin levels and a higher (but not significant) incidence of acute chest syndrome (ACS), vasoocclusive crisis (VOC), splenic sequestration, transfusions, and history of intermittent bronchospasm compared to with patients with hemoglobinopathies Hb SC, Hb Sbt and Hb SF (Group II; n = 8). Both groups had elevated FRC, decreased maximum expiratory flows at FRC (V'max,FRC), and decreased time needed to reach peak expiratory flow (tme/tE), suggesting lower airway obstruction (LAO) and hyperinflation. Restrictive disease was found in only three patients of Group I. Our findings suggest that in sickle cell disease (especially among patients with Hb SS), abnormal lung function (predominantly LAO) may be present in early infancy. Airway reactivity may play a role in the pathogenesis, but the relation to VOC or ACS remains unclear.
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PMID:Lung function in infants with sickle cell disease. 936 61

Cerebrovascular accident (CVA) is a major complication of sickle cell disease. The incidence and mortality of and risk factors for CVA in sickle cell disease patients in the United States have been reported only in small patient samples. The Cooperative Study of Sickle Cell Disease collected clinical data on 4,082 sickle cell disease patients enrolled from 1978 to 1988. Patients were followed for an average of 5.2 +/- 2.0 years. Age-specific prevalence and incidence rates of CVA in patients with the common genotypes of sickle cell disease were determined, and the effects of hematologic and clinical events on the risk of CVA were analyzed. The highest rates of prevalence of CVA (4.01%) and incidence (0.61 per 100 patient-years) were in sickle cell anemia (SS) patients, but CVA occurred in all common genotypes. The incidence of infarctive CVA was lowest in SS patients 20 to 29 years of age and higher in children and older patients. Conversely, the incidence of hemorrhagic stroke in SS patients was highest among patients aged 20 to 29 years. Across all ages the mortality rate was 26% in the 2 weeks after hemorrhagic stroke. No deaths occurred after infarctive stroke. Risk factors for infarctive stroke included prior transient ischemic attack, low steady-state hemoglobin concentration and rate of and recent episode of acute chest syndrome, and elevated systolic blood pressure. Hemorrhagic stroke was associated with low steady-state hemoglobin and high leukocyte count.
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PMID:Cerebrovascular accidents in sickle cell disease: rates and risk factors. 941 96


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