bims-conane 2024-11-10 papers

Issue of 2024‒11‒10
five papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo

Clin Ther. 2024 Nov 01. pii: S0149-2918(24)00287-X. [Epub ahead of print]

Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England.

Chuka Udeze, Nelly F Ly, Fiona C Ingleby, Sophia D Fleming, Sarah C Conner, Jo Howard, Nanxin Li, Farrukh Shah.

PURPOSE: Patients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England.METHODS: This longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period.
FINDINGS: Of 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years.
IMPLICATIONS: Patients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.

Keywords: Clinical complications; Economics; Healthcare resource utilization; Mortality; Transfusion-dependent β-thalassemia

DOI: https://doi.org/10.1016/j.clinthera.2024.09.024

Prenat Diagn. 2024 Nov 02.

Heterozygous Beta-Thalassaemia in Pregnancy: Two Rare Causes of Severe Fetal Anemia Requiring Intrauterine Blood Transfusions.

Eva van der Meij, Frans J W Smiers, Tamara T Koopmann, Ingrid Krapels, Kaatje LePoole, Enrico Lopriore, Johanna M Middeldorp, Claudia S Ootjers, Volkher Scharnhorst, Hubertina C J Scheepers, Cornelis L Harteveld, E J T Joanne Verweij.

AIM: In this article, we present two cases of severe fetal hemolytic anemia based on a beta-thalassaemia trait inherited from a single parent.RESULTS: These cases, presented at 20 and 28 weeks' gestation, necessitated intra-uterine blood transfusions. This occurrence is remarkable because it challenges the common assumption that beta-thalassaemia typically has no prenatal implications regarding fetal anemia. Both fetuses inherited a rare heterozygous mutation from their mother, resulting in gamma-thalassaemia-related anemia. In the first case, the anemia was related to a deletion in the beta locus control region (βLCR) and in the second case, a deletion on chromosome 11p15.4 was the cause. These mutations not only affect the beta chain production, but also the gamma chain production, leading to a reduction in the synthesis of HbF, ineffective erythropoiesis and consequently, perinatal hemolytic anemia.
CONCLUSION: Clinicians should be vigilant regarding these rare mutations in families with a history of beta-thalassaemia as the fetal clinical consequences can be severe and intra-uterine blood transfusions may prove life-saving for these fetuses.

DOI: https://doi.org/10.1002/pd.6695

Hemoglobin. 2024 Nov 04. 1-7

Existing Tubular Injury in β-Thalassemia Major Patients Receiving Iron Chelating Agents with Normal Creatinine Level in East Java, Indonesia.

Pradana Zaky Romadhon, Ami Ashariati, Siprianus Ugroseno Yudho Bintoro, Satriyo Dwi Suryantoro, Choirina Windradi, Bagus Aulia Mahdi, Krisnina Nurul Widyastuti, Etha Dini Widiasi, Kartika Prahasanti, Aditea Etnawati Putri, Narazah Mohammad Yusoff.

Patients suffering from thalassemia are recipients of routine transfusions leading to hemosiderosis. Taking iron chelating agents is mandatory. Several studies have shown different results regarding the occurrence of kidney complications in thalassemia patients who received iron-chelating agents. In this study, we were looking for kidney complications by examining human NAG urine/serum and NGAL urine/serum in thalassemia community in East Java community. The study was conducted cross-sectionally in the thalassemia community in East Java with a total sample of 91 patients aged 13-48 years. All thalassemia patients filled in demographic data, transfusion routines, duration of taking iron chelating agents, and length of time diagnosed with thalassemia. Laboratory tests included routine blood tests for ferritin, ureum, serum creatinine, human NAG urine or serum, and human NGAL urine or serum. Comparison tests (t-test, Mann-Whitney, and ANOVA, Kruskal-Wallis) were conducted to see if there were significant differences in the levels of human NAG urine and human NGAL urine serum based on age, sex, blood group, duration of transfusion, routine of transfusion, duration of taking iron chelating agents, and types of iron chelating drugs. Multivariate analysis was conducted to see whether some of these categories were related to abnormalities in human NAG urine or serum and human NGAL urine or serum. All 91 patients had normal creatinine values, yet some had abnormal serum NAG. There is a significant difference in urine human NAG and urine human NGAL levels at ages over 23 years (p = 0.05 and p = 0.01). Significant differences in human NGAL serum were also found in working and student patients (p = 0.028). Serum NGAL also differed in those taking deferasirox (p = 0.030) and significantly different human NGAL urine was also found in iron overload status (Ferritin ≥ 1000 ng.ml) (p = 0.006). There is no difference between human NAG urine/serum and human NGAL urine/serum based on sex, body mass index, blood type, hemoglobin less than 10 g/dl, routine transfusion once a month, duration of using iron chelation for more than 10 years, or splenomegaly status (splenomegaly, splenectomy, or no splenomegaly). The multivariate logistic regression results showed that age above 23 was a factor associated with abnormal urine human NAG levels (aOR = 3.79, 95% CI = 1.08-13.28). Students (aOR = 4.89, 95% CI = 1.48-16.16) with ages above 23 years (aOR = 3.69, 95% CI = 1.09-12.43) showed higher risk for an abnormal serum human NGAL levels. Patients with beta-thalassemia major exhibit noticeable tubular damage. Further research is encouraged to determine other factors behind tubular damage in the thalassemia community, particularly in Indonesia.

Keywords: Tubular injury; chelating agents; iron; renal marker; β-thalassemia

DOI: https://doi.org/10.1080/03630269.2024.2414102

Hemoglobin. 2024 Nov 05. 1-4

Phenotypic Analysis of the HBA2: C.95 G > A Mutation in China.

Jian-Lian Liang, Yi-Yuan Ge, Long-Xu Xie, Guang-Kuan Zeng, Xiao-Hua Yu, Yu-Wei Liao, Li-Li Liu, Yan-Bin Cao, Bai-Ru Lai, Yan-Qing Zeng, Yu-Chan Huang, Li-Ye Yang.

This study aimed to analyze the clinical phenotype of the HBA2: c.95G>A mutation in the Chinese population and to provide guidance for clinical diagnosis and genetic counseling. Peripheral blood samples were collected from 16 patients, including 6 newborns, 2 children, and 8 adults. Hematological parameters and hemoglobin electrophoresis were analyzed, and genotypes were identified using methods such as PCR combined with reverse dot blot (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), and DNA sequencing. The results showed that 10 patients had mild anemia, 2 had moderate anemia, and 12 exhibited microcytic hypochromic features with MCV values ranging from 53 to 74.7 fl and MCH values from 16.2 to 25.4 pg. Additionally, 3 cases displayed obvious HbH + HbBarts bands (>15%). Among the 16 cases, various combinations of the HBA2: c.95G>A mutation were observed: one case had -α3.7 combined with HBA2: c.95G>A, another had -α4.2 combined with HBA2: c.95G>A, and five had -SEA combined with HBA2: c.95G>A, while the remaining cases were HBA2: c.95G>A heterozygotes. The study concludes that the HBA2: c.95G>A mutation in the α2 globin gene causes α+ thalassemia. When this mutation is combined with the Southeast Asian deletion (-SEA), it results in HbH disease, characterized by moderate microcytic hypochromic anemia and the presence of HbH + HbBarts bands.

Keywords: DNA sequencing; HBA2; phenotype; α-thalassemia

DOI: https://doi.org/10.1080/03630269.2024.2424303