ELLIOTT P contact VICHINSKY

..To evaluate these therapies optimally, recommendations for improving clinical trial design in hemoglobinopathies are discussed...

..These patients often require comprehensive, multidisciplinary care. This chapter focuses on screening, diagnosis, and treatment approaches for patients with Hb H disease...

..Since its cause is largely unknown, therapy is supportive. Pilot studies with improved diagnostic techniques suggest that infection and fat embolism are underdiagnosed in patients with the syndrome...

..Comprehensive services that address language and social barriers as well as access to Hb F-enhancing agents and transfusions are needed...

..Characterization of the new spectrum of this ancient disease, now predominated by minority groups, is essential for optimizing survival...

..As with any new agent, it is important that treating physicians are familiar with the adverse event profile of deferasirox and how the associated effects can be readily managed to ensure optimal use of this important treatment...

..However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment...

..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...

..Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease...

..As evidence suggests more patients with SCD could benefit from regular transfusion therapy, it is apparent that greater awareness of the need to monitor and treat iron overload in transfused patients is required...

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..Universal newborn screening has been adopted in several regions with DNA confirmatory testing. These advances have resulted in ethical dilemmas for the family and the provider...

..NO regulates blood vessel tone, endothelial adhesion, and the severity of ischaemia-reperfusion injury and anaemia in SCD. Although NO is difficult to administer, its precursor, L-arginine, is an oral supplement...

..The purpose of this study was to determine if a multicenter trial could implement a transfusion program utilizing phenotypically matched blood to reduce alloimmunization...

..Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years...

..To measure body composition in patients with thalassemia and explore its relationship to abnormal growth and bone mass...

..Erythrocyte release of arginase during hemolysis contributes to the development of PHT. Therapies that maximize arginine and nitric oxide bioavailability may benefit patients with thalassemia...

..We hypothesized that increased arginase activity and dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, and patient outcomes...

..Although transfusion requirements increased in most patients, iron burden was not necessarily increased...

..The objective of this study was to evaluate the current standard of care in monitoring iron overload and related complications in patients with SCD compared to thalassemia (Thal)...

..After 5 years of follow-up, a subset of patients remained off transfusions. Hydroxyurea should be considered for a subset of Hb E-beta 0-thalassemia patients...

..Finally, the absence of a detectable change in ferritin mRNA indicates insufficient oxidative stress to significantly activate MARE/ARE promoters...

..Education and frequent noninvasive LIC assessments can improve adherence and iron burden. Elevated LIC does not necessarily reflect concurrent noncompliance; however, it can be an indication of nonadherence in the past...

..3 (95% confidence interval 4.9-60.4). The divergent clinical spectrum for PHT between adults and children may point to different age-specific mechanisms or biological expression of PHT...

..This first report of a marked increase in the ferritin H/L-subunit ratio may point to an underlying mechanism of disease in this enigmatic disorder...

..With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation...

..Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture...

..The authors have previously shown that Arg supplementation alone induces a paradoxical decrease in NO metabolite (NO(x)) production...

..However, the efficacy of hip core decompression to prevent the progression of osteonecrosis in these patients is still controversial...

..Review of the blood indices and serum iron and ferritin markers may alert the clinician to most disorders. Further research is likely to define the scope and approach to clinical diagnosis of the diseases of iron metabolism...

..Early diagnosis during newborn screening or infancy has enabled the observation of the natural history of hemoglobin H disease, a subtype of α-thalassemia...

..Presented data suggest that all patients with thalassemia undergo QOL assessment so that interventions focused on affected domains can be implemented...

..Other screening modalities, including the transtelephonic event recorder, should be evaluated in arrhythmia surveillance...

..We evaluated bone mineral density (BMD) and risk factors for poor bone mineralization in children with sickle cell anemia (SCA)...

..Continuous monitoring of toxicity and growth is required...

..Improvements in PGD therapy's efficacy and cost will make this a more viable option for affected families...

..This study underscores the role of platelet activation in the development of PAH and stresses its occurrence even among patients who are regularly transfused, especially those who are older and have had splenectomies...

..However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time...

..These findings underscore the disappointing results of hydroxyurea treatment in clinical trials and the importance of examining the effect on RBC characteristics for the development and understanding of HbF-enhancing agents...

..CONCLUSIONS: The CHOHES appears to be an easy-to-use, valid, and reliable assessment tool and should be considered for use in the routine clinical evaluation of SCD patients with AVN...

..Our findings indicate that higher levels of micronuclei frequencies are present in thalassemic RBCs...

..Decreased erythrocyte glutathione and glutamine levels contribute to alterations in the erythrocyte redox environment, which may compromise erythrocyte integrity, contribute to hemolysis, and play a role in the pathogenesis of PH of SCD...

..Guidelines for the management of PH in thalassemia have not yet been established; however, clinical trials are ongoing in an effort to guide future therapy...

..Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities...

..These preliminary observations, made over the last 7 years, provide directions for future research into this increasingly important disease...

..The Tanner stage transitions took place at appropriate ages. CONCLUSIONS: Hydroxyurea treatment had no adverse effect on height or weight gain or pubertal development in school-aged children with SCA...

..To determine the dose tolerance, safety, and pharmacokinetics of a single oral dose of ICA-17043 in patients with sickle cell disease...

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..In summary, if this study is successful, it will change the approach to Hb E/B worldwide and result in improved quality of life and decreased mortality. (End of Abstract) ..

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