Among patients with sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and infection, especially community-acquired pneumonia. Among older patients and those with neurologic symptoms, the syndrome often progresses to respiratory failure. Treatment with transfusions and bronchodilators improves oxygenation, and with aggressive treatment, most patients who have respiratory failure recover.

A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications.

Among children and adults with sickle cell anemia, the median number of pain crises over 48 weeks was lower among those who received oral therapy with l-glutamine, administered alone or with hydroxyurea, than among those who received placebo, with or without hydroxyurea. (Funded by Emmaus Medical; ClinicalTrials.gov number, NCT01179217 .).

Context Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. Objective To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. Design, Setting, and Participants Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level ≤10 mg/dL) aged 19 to 55 years and of African descent (n=149) or community controls (Hb AA and normal hemoglobin level) (n=47). Participants were stratified on age, sex, and education. Main Outcome Measures The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. Results The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, −5.50; 95% confidence interval {CI}, −9.55 to −1.44]; P =.008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, −5.19; 95% CI, −9.24 to −1.13]; P =.01), working memory (90.75 vs 95.25 [mean difference, −4.50; 95% CI, −8.55 to −0.45]; P =.03), processing speed (86.50 vs 97.95 [mean difference, −11.46; 95% CI, −15.51 to −7.40]; P <.001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. Conclusion Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.

© F e r r a t a S t o r t i F o u n d a t i o nN o c o m m e r c i a l u s e metabolite (NO x ) levels. 16 The lowest arginine levels were found in children requiring admission for VOE, 16 with arginine levels returning to baseline during convalescence in the hospital. Of interest, low plasma arginine alone was a sensitive predictor for admission, 16 while NO x levels were not, suggesting a function for arginine bioavailability in VOE severity that goes beyond NO. Although supplemental arginine increases plasma NO x in normal controls, when given to SCD patients at steady-state, a paradoxical decrease in NO x occurs that is not overcome by higher doses, 20 indicating that arginine is metabolized differently in patients with SCD than in healthy volunteers. However, when a single dose of arginine is given to patients with SCD during VOE, there is a robust dosedependent increase in plasma NO x . 20 Based on these promising data, we designed a randomized, placebo-controlled trial to determine the safety and efficacy of arginine therapy in children with SCD requiring hospitalization for severe pain necessitating parenteral narcotics. Methods Study designThis study was a single-center, prospective, randomized, double-blind, placebo-controlled, phase 2 trial designed to explore the effectiveness of the arginine intervention in participants with SCD requiring hospitalization for VOE. Data outcome measures included length of stay (LOS) in hospital (days), total narcotic use over the course of the emergency department visit and hospitalization (mg/kg), and pain scores (10-cm linear visual analog scale and Faces Pain Scale). Further details are provided in the Online Supplementary Methods.Standard intravenous (IV) opioid analgesic equivalents were used: 10 mg morphine sulfate = 100 mg meperidine = 2 mg hydromorphone hydrochloride. A hospital admission for a pain episode was considered a distinct event if it occurred more than 2 weeks after a previous pain episode requiring parenteral opioid therapy.The study protocol was approved by the Institutional Review Board at the Children's Hospital & Research Center at Oakland (CHRCO): informed consent was obtained for all patients enrolled, and assent was obtained from all children age 7 years and older. Children with an established diagnosis of SCD age 3-19 years with VOE requiring parenteral opioids and admission to hospital were recruited from emergency departments, hematology clinics, day hospitals and wards. Patients were recruited as a convenience sample during times when the principal investigator or study nurse was on-site and available to consent, a legal guardian was present, and the research pharmacist was available to perform the randomization.Patients were consented within 24 hours of admission to the hospital and randomized to receive IV or oral (PO) study drug, Larginine hydrochloride (100 mg/kg/dose three times/day with a maximum dose of 10 g for 15 doses or until discharge, whichever occurred first) or placebo. Placebo capsules appeared identical to the s...

Background and Study Objectives Transfusions are the primary therapy for thalassemia but have significant cumulative risks. In 2004, the Centers for Disease Control and Prevention (CDC) established a national blood safety monitoring program for thalassemia. The purpose of this report is to summarize the patient population as well as previous non-immune and immune transfusion complications at the time of enrollment into the program. A focus on factors associated with allo- and auto-immunization in chronically transfused patients and a description of blood product preparation and transfusion practices at the participating institutions are included. Study Design and Methods The CDC Thalassemia Blood Safety Network is a consortium of thalassemia centers, longitudinally following patients to determine transfusion-related complications. Enrollment occurred from 2004 through 2012 and annual data collection is ongoing. Demographic data, transfusion history, and previous transfusion and non-transfusion complications were summarized for patients enrolled between 2004 and 2011. Logistic analyses of factors associated with allo- and auto-immunization were developed. Summary statistics of infections reported at the time of enrollment were also calculated. Results The race/ethnicity of the 407 thalassemia patients enrolled in the Network was predominantly Asian or Caucasian and 27% were immigrants. The average age was 22.3 years ± 13.2 and patients received an average total number of 149 ± 103.4 units of red blood cells. Iron-induced multi-organ dysfunction was common despite chelation. At study entry, 86 patients had previously been exposed to possible transfusion-associated pathogens, including Hepatitis-C (61), Hepatitis B (20), Hepatitis A (3), Parvovirus (9), HIV (4), malaria (1), staphylococcus aureus (1) and babesia (1). As 27% of the population was born outside of the United States (India, Pakistan, Thailand, China, Vietnam and Iran accounting for 57%), the source of infection cannot be unequivocally tied to transfusion. In total, 24% of transfused patients were reported to have possible transfusion-associated pathogens. Transfusion reactions occurred in 48% of patients, including allergic, febrile, and hemolytic; 19% of transfused patients were alloimmunized (defined as a having an antibody to a foreign red blood cell antigen). The most common antigens were E, Kell and C. One hemolytic reaction to an anti-Mia antibody was noted. Years of transfusion was the strongest predictor of alloimmunization. However, initiating transfusions in infancy may induce immune tolerance. Autoantibodies occurred in 6.5% and were predicted by previous alloimmunization (p < .0001). Local institutional transfusion policies, rather than patient characteristics, were the major determinants in the preparation of red-blood cells for transfusion. Conclusion Hemosiderosis and immunologic and non-immunologic transfusion reactions are major problems in thalassemia patients. Infections continue to be a problem in thalassemia and new pathogen...

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Orthopedic disease affects the majority of sickle cell anemia patients of which aseptic necrosis of the hip is the most common, occurring in up to 50% of patients. We conducted a multicentered study to determine the perioperative complications among sickle cell patients assigned to different transfusion regimens prior to orthopedic procedures: 118 patients underwent 138 surgeries. The overall serious complication rate was 67%. The most common of these were excessive intraoperative blood loss, defined as in excess of 10% of blood volume. The next most common complication was sickle cell-related events (acute chest syndrome or vaso-occlusive crisis), which occurred in 17% of cases. While preoperative transfusion group assignment did not predict overall complication rates, higher risk procedures were associated with significantly higher rates of overall complications. Transfusion complications were experienced by 12% of the patients. Two patients died following surgery. Both deaths were associated with an acute pulmonary event. The 52 patients undergoing hip replacements experienced the highest rate of complications with excessive intraoperative blood loss occurring in the majority of patients. Sickle cell-related events occurred in 19% of patients, and surgical complications occurred after 15% of hip replacements and included postoperative hemorrhage, dislocated prosthesis, wound abscess, and rupture of the femoral prosthesis. There were twenty-two hip coring procedures. Acute chest syndrome occurred in 14% of the patients. Overall, decompression coring was a safer, shorter operation. A randomized prospective trial to determine the perioperative and long-term efficacy of core decompression for avascular necrosis of the hip in sickle cell disease is needed. In conclusion, this study demonstrates a high rate of perioperative complications despite compliance with sickle cell perioperative care guidelines. Pulmonary complications and transfusion reactions were common. This study supports the results previously published by the National Preoperative Transfusion in Sickle Cell Disease Group. These results stated that a conservative preoperative transfusion regimen to bring hemoglobin concentration to between 9 and 11 g/dl was as effective as an aggressive transfusion regimen in which the hemoglobin S level was lowered to 30%.