Tamara New

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series.

Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization. Alloimmunized patients have an increased risk of serious hemolytic transfusion reactions (HTRs) and may not receive adequate RBC transfusion support due to lack of compatible RBC units.

SickleREMOTE: A two-way text messaging system for pediatric sickle cell disease patients

Sickle cell disease, the most common hemo-globinopathy in the world, affects patient lives from early childhood. Effective care of sickle cell disease requires frequent medical monitoring, such as tracking the frequency, severity, and duration of painful events. Conventional monitoring includes paper- or web-based reporting diaries. These systems require that patients carry forms, which are easily lost, or laptop computers, which are impractical to scale to large populations. Both are prone to sporadic use by older adolescents due to lack of reminders. In this paper, we design and prototype a Sickle cell disease REporting and MOnitoring TElemedicine system (SickleREMOTE), aiming to resolve limitations of conventional monitoring diaries. This monitoring system is configured as automated short message service text (SMS-text) messages that arrive at a mobile phone anywhere on a cellular network. The messages may be reminders to encourage treatment adherence or questionnaires to collect self-assessed clinical data relating to treatment adjustments. Patients respond to the messages using pre-determined templates and a cloud database parses and stores messages automatically. Providers use a web-based interface to view, analyze, and download collected data. SickleREMOTE is developed by Georgia Institute of Technology in conjunction with Childrens Healthcare of Atlanta (CHOA). System effectiveness will be evaluated using a trial of 30 adolescents with sickle cell disease and measured by response rate, time to response, error rate, and correspondence with data collected by telephone calls.

Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in children with sickle cell disease: less prevalent and predictive than previously thought?

Although elevated tricuspid regurgitant velocity (TRV), an echocardiographic marker for pulmonary hypertension, has previously been tied to mortality in adult patients with sickle cell disease, recent data demonstrated that it correlates poorly with catheterization findings. We describe the largest echocardiographic evaluation of pediatric patients with sickle cell disease to date, specifically the results of a protocol whereby a TRV≥250 cm/s prompted further evaluation. We investigated if elevated TRV would independently identify patients at risk for increased morbidity. A clinical echocardiographic database containing 630 patients with sickle cell disease was retrospectively reviewed; 120 patients (19%) met inclusion criteria and were compared 1:1 to randomly selected age-matched controls from the same database. By multivariate analysis, the elevated TRV cohort did not differ from controls in likelihood of acute chest episodes, hospitalization, or stroke. The study cohort’s mean TRV in fact decreased to 242±33 cm/s at follow-up without a discernible and comprehensive intervention to explain the improvement. Three patients had catheterization-proven pulmonary hypertension. In conclusion, elevated TRV in children with sickle cell disease is less prevalent than previously thought and is not independently associated with increased short-term morbidity.

Widespread Pain among Youth with Sickle Cell Disease Hospitalized with Vasoocclusive Pain: A Different Clinical Phenotype?

Objectives: The purpose of this study was to describe the clinical phenotype of widespread pain (WSP) among youth with sickle cell disease (SCD) hospitalized with vasoocclusive pain. Materials and Methods: One hundred fifty-six youth with SCD, between 7 and 21 years of age hospitalized at 4 children’s hospitals for a vasoocclusive episode were evaluated. Data were collected during 1 day of the hospitalization. Results: Using the 2010 American College of Rheumatology guidelines, 21.8% of patients were identified as having WSP (pain in 7 or more unique body locations). Patients classified as having WSP had higher pain intensity (6.5 vs. 5.6; t=2.19, P=0.03) higher pain burden (13.0 vs. 9.8; t=3.09, P=0.002), higher acute functional disability (22.1 vs. 16.5; t=2.43, P=0.016), higher chronic functional disability (30.4 vs. 22.2; t=2.31, P=0.02), lower positive affect (22.9 vs. 27.6; t=2.23, P=0.027), and lower quality of life (56.2 vs. 62.9; t=1.99, P=0.049) than those youth with SCD without WSP. Discussion: Assessment of WSP may identify a unique clinical phenotype of youth with SCD with differing treatment needs.

Management of refractory pain in hospitalized adolescents with sickle cell disease: changing from intravenous opioids to continuous infusion epidural analgesia.

Background: Prolonged hospitalizations for sickle cell disease painful episodes are not uncommon, as analgesic options are often suboptimal. Observations: Seven patients (15.4±3.7 y, 6 females) were treated with epidural analgesia for refractory pain. The median duration of epidural catheter placement was 4 days (interquartile range, 3 to 6 d). Mean pain scores changed from 6.8±2.7 to 4.8±2.2, whereas mean daily parenteral opioid requirements changed from 79.7±100.4 to 13.0±13.1 mg of morphine equivalents. Conclusion: Continuous epidural analgesia is an alternative to continuing intravenous opioids in sickle cell disease patients with refractory pain, and may reduce opioid-related side effects and facilitate transition to oral analgesics.

A phase 3 trial of l-glutamine in sickle cell disease

BACKGROUND Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical‐grade l‐glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result in fewer episodes of sickle cell–related pain. METHODS In a multicenter, randomized, placebo‐controlled, double‐blind, phase 3 trial, we tested the efficacy of pharmaceutical‐grade l‐glutamine (0.3 g per kilogram of body weight per dose) administered twice daily by mouth, as compared with placebo, in reducing the incidence of pain crises among patients with sickle cell anemia or sickle β0‐thalassemia and a history of two or more pain crises during the previous year. Patients who were receiving hydroxyurea at a dose that had been stable for at least 3 months before screening continued that therapy through the 48‐week treatment period. RESULTS A total of 230 patients (age range, 5 to 58 years; 53.9% female) were randomly assigned, in a 2:1 ratio, to receive l‐glutamine (152 patients) or placebo (78 patients). The patients in the l‐glutamine group had significantly fewer pain crises than those in the placebo group (P=0.005), with a median of 3.0 in the l‐glutamine group and 4.0 in the placebo group. Fewer hospitalizations occurred in the l‐glutamine group than in the placebo group (P=0.005), with a median of 2.0 in the l‐glutamine group and 3.0 in the placebo group. Two thirds of the patients in both trial groups received concomitant hydroxyurea. Low‐grade nausea, noncardiac chest pain, fatigue, and musculoskeletal pain occurred more frequently in the l‐glutamine group than in the placebo group. CONCLUSIONS 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.)

Tissue Doppler Imaging-derived Diastolic Function Assessment in Children With Sickle Cell Disease and Its Relation With Ferritin.

Diastolic dysfunction has been shown to occur earlier than systolic dysfunction in iron overload states in adult patients with sickle cell disease (SCD). Tissue Doppler imaging (TDI)-derived E/E′ has emerged as a noninvasive marker of diastolic function. We sought to determine diastolic function in children with SCD and study its relation with iron overload. A retrospective review of medical records of 225 pediatric patients with SCD who received an echocardiogram between January 2008 and December 2012 was performed. Echocardiographic measures including M-mode, spectral Doppler, and TDI-derived E/E′ were compared with previously published data in healthy children. The left ventricular end-diastolic and end-systolic dimensions were significantly higher in SCD (P<0.0001) and the shortening fraction was similar (P=0.66). E/E′ ratio was significantly higher in SCD at the mitral annulus, septum, and tricuspid annulus. In 54% of subjects, the septal E/E′ was >8, indicating elevated left ventricular filling pressure. However, there was no significant correlation between ferritin level and E/E′ ratios. Pediatric patients with SCD have a high prevalence of elevated estimated left ventricular filling pressure, but this does not correlate with ferritin levels.