Clinical Features of β-Thalassemia and Sickle Cell Disease

McGann, Patrick T.; Nero, Alecia; Ware, Russell E.

doi:10.1007/978-1-4939-7299-9_1

Cited by 16 publications

(11 citation statements)

References 92 publications

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“…1 In the United States, approximately 100,000 persons are affected, 2 most of whom have numerous acute and chronic medical complications that lead to poor quality of life and early death. 1,3 On a global scale, the incidence of sickle hemoglobinopathies is greatest in sub-Saharan Africa, with more than 300,000 babies with sickle cell disease born annually, representing approximately 1% of births in the region. 4…”

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Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

et al. 2019

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BACKGROUND Hydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings. METHODS We enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell–related events, transfusions, and survival). RESULTS A total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88). CONCLUSIONS Hydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731.)

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Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

et al. 2019

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“…β-thalassemia/HbE is one of the most prevalent diseases in Thailand and other countries, and patients show varying degrees of anemia and abnormally high numbers of NRBCs. [23][24][25][26] The increased number of NRBCs in severe β-thalassemia/HbE has been shown to interfere with the lymphocyte counts obtained using several automated cell counters. 9,10 Barnes et al evaluated the performance of the DxH-800 on the detection of blast cells and found that its false positive rate when differentiating white blood cells in abnormal specimens was lower than that of another automated instrument.…”

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Accuracy of lymphocyte counts from UniCel DxH 800 in β-thalassemia/HbE patients having various numbers of nucleated red blood cells

Timilsena

Ardsiri

Lerdwana

et al. 2022

Asian Pac J Allergy Immunol

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Background:The UniCel® DxH-800 is an automated cell counter widely used in laboratories. However, the effects of increased nucleated red blood cells (NRBCs) on the lymphocyte counts obtained using the UniCel DxH-800 have not been fully elucidated.Objective: The study's objective was to compare lymphocyte counts obtained using the DxH-800 and those obtained using flow cytometry in various ranges of NRBCs. Methods:This cross-sectional study analyzed 25 healthy volunteers and 69 β-thalassemia/HbE patients. The numbers of lymphocytes were determined using a UniCel DxH-800 and a standard flow cytometer using counting beads.Results: In healthy volunteers, regression analysis of the lymphocyte counts using the two approaches showed an r 2 0.85 and a p < 0.0001, and a Bland-Altman plot showed mean bias of +264 cells/μL. In β-thalassemia/HbE patients, regression analysis of the lymphocyte counts obtained using an automated cell counter and a flow cytometer showed an r 2 of 0.06, a p = 0.028, and a Bland-Altman plot showed the mean bias of +1,509 cells/μL. In addition, a high degree of discrepancy in the lymphocyte counts was observed in β-thalassemia/HbE patients who had NRBCs > 100,001 cells/μL. Conclusions:The present study demonstrated that the UniCel DxH-800 performed well in enumerating lymphocytes in specimens that contained various numbers of NRBCs. However, a high number of NRBCs may interfere with lymphocyte counts obtained using the counter.

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“…This polymerization results in elongated and stiffened RBCs that cause vaso‐occlusion due to the decreased deformability and inability to easily travel through blood vessels. Painful vaso‐occlusive crises are the hallmark of SCD, but without adequate treatment, sickled RBCs and the associated hemolytic anemia results in innumerable acute and chronic clinical complications, including increased susceptibility to invasive bacterial infection due to splenic autoinfarction, acute splenic sequestration crisis, acute chest syndrome, stroke, chronic organ damage, and shortened lifespan 3 . Without early diagnosis and appropriate disease‐modifying treatment, SCA results in significant morbidity and early mortality.…”

Section: Overview Of Sickle Cell Diseasementioning

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Changing the Clinical Paradigm of Hydroxyurea Treatment for Sickle Cell Anemia Through Precision Medicine

Dong

McGann

2020

Clin Pharma and Therapeutics

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Sickle cell anemia (SCA) is a common and devastating inherited blood disorder, affecting millions of people across the world. Without treatment, SCA results in tremendous morbidity and early mortality. Hydroxyurea is the primary and most well‐established pharmacologic therapy with proven benefits to ameliorate the clinical course of SCA, primarily due to its ability to increase the expression of fetal hemoglobin (HbF), which prevents sickling of red blood cells. The optimal induction of HbF depends upon selection and maintenance of the proper dose that maximizes benefits and minimizes toxicity. Due to the significant interpatient variability in hydroxyurea pharmacokinetics, pharmacodynamics, and dosing, most patients treated with hydroxyurea receive suboptimal doses and have only modest treatment responses. Recognizing this variability, using a precision medicine approach, we developed and prospectively evaluated an individualized dosing model for children with SCA, designed to optimize the hydroxyurea dose and clinical response. We utilize novel laboratory methods and a sparse sampling strategy requiring only 10 μL of blood collected 15 minutes, 60 minutes, and 180 minutes after a test dose. We use Bayesian adaptive control to estimate hydroxyurea exposure and to select an individual, optimal starting dose. This dosing model has resulted in HbF responses >30–40%, levels beyond what is achieved with traditional weight‐based dosing and trial and error dose escalation. This hydroxyurea dosing strategy, if widely implemented, has the potential to change the treatment paradigm of hydroxyurea therapy and improve outcomes for the millions of patients with SCA across the world.

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Clinical Features of β-Thalassemia and Sickle Cell Disease

Cited by 16 publications

References 92 publications

Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

Accuracy of lymphocyte counts from UniCel DxH 800 in β-thalassemia/HbE patients having various numbers of nucleated red blood cells

Changing the Clinical Paradigm of Hydroxyurea Treatment for Sickle Cell Anemia Through Precision Medicine

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