@article{3122192,
    title = "Activin-A is elevated in patients with thalassemia major and double heterozygous sickle cell/beta-thalassemia and correlates with markers of hemolysis and bone mineral density",
    author = "Voskaridou, E. and Ntanasis-Stathopoulos, I. and Christoulas, D. and Dimopoulou, M. and Komninaka, V. and Repa, K. and Papatheodorou, A. and Terpos, E.",
    journal = "Annals of Hematology",
    year = "2019",
    volume = "98",
    number = "7",
    pages = "1583-1592",
    publisher = "Springer-Verlag",
    issn = "0939-5555, 1432-0584",
    doi = "10.1007/s00277-019-03695-x",
    keywords = "activin A;  bilirubin;  ferritin;  lactate dehydrogenase;  activin;  activin A;  biological marker, adult;  aged;  Article;  bilirubin blood level;  bone density;  cohort analysis;  controlled study;  correlation analysis;  dual energy X ray absorptiometry;  female;  femoral neck;  ferritin blood level;  hemolysis;  heterozygous sickle cell beta thalassemia;  human;  lactate dehydrogenase blood level;  lumbar spine;  major clinical study;  male;  priority journal;  prospective study;  protein blood level;  reticulocyte count;  sickle cell anemia;  sickle cell beta thalassemia;  thalassemia intermedia;  thalassemia major;  beta thalassemia;  blood;  clinical trial;  genetics;  heterozygote;  middle aged, Activins;  Adult;  Aged;  Anemia, Sickle Cell;  beta-Thalassemia;  Biomarkers;  Bone Density;  Female;  Hemolysis;  Heterozygote;  Humans;  Male;  Middle Aged;  Reticulocyte Count",
    abstract = "Despite the advances in the management of hemoglobinopathies, further insight into disease pathophysiology is necessary to improve our therapeutic approach. Activin-A has emerged as a regulator of erythropoiesis and bone turnover in malignant disorders; however, clinical data in hemoglobinopathies are currently scarce. Thus, we aimed to investigate the role of activin-A among hemoglobinopathy patients and evaluate the rationale of its targeting. Circulating levels of activin-A were measured in patients (n = 227) with beta-thalassemia major (TM) (n = 58), beta-thalassemia intermedia (TI) (n = 43), double heterozygous sickle cell/beta-thalassemia (HbS/beta-thal) (n = 109), or homozygous sickle cell disease (n = 17), and we explored possible correlations with clinical and laboratory data. Seventeen age- and gender-matched, healthy individuals served as controls. Bone marrow density (BMD) was determined using dual-energy X-ray absorptiometry. TM and HbS/beta-thal patients had elevated activin-A compared to controls (p = 0.041 and p = 0.038, respectively). In TM patients, high circulating activin-A showed strong correlations with hemolysis markers, namely reticulocyte count (p = 0.011) and high lactate dehydrogenase (LDH; p = 0.024). Similarly, in HbS/beta-thal patients, activin-A showed positive correlations with indirect bilirubin (p < 0.001), ferritin (p = 0.005), and LDH (p = 0.044). High activin-A correlated with low Z-score of both lumbar spine BMD in TI patients (p < 0.01) and femoral neck BMD in TM patients (p < 0.01). Serum activin-A is elevated in patients with TM and HbS/beta-thal and correlates with markers of hemolysis and low BMD. These data support a role of activin-A in the biology of these disorders and provide further rationale for the broader clinical development of activin-A inhibitors in this setting. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature."
}