Thalassemia 2016: Modern medicine battles an ancient disease

Abstract

Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

Extracellular Vesicle Characteristics in β-thalassemia as Potential Biomarkers for Spleen Functional Status and Ineffective Erythropoiesis

“…As there is no physiological mechanism to excrete iron from the body, patients require lifelong chelation therapy to prevent iron overload (Rund and Rachmilewitz, 2005). Reduction of erythroid cell lifespan, free-iron toxicity, and deposition of excess iron in vital organs are the major factors responsible for the functional and physiological abnormalities found in patients with thalassemia (Rund and Rachmilewitz, 2005; Koren et al, 2010; Breuer et al, 2012; Rund, 2016). …”

Laboratory diagnosis of thalassemia

“…The unstable free globin chain tetramers precipitate in erythroid cells leading to premature cell death inside and outside (peripheral hemolysis) the bone marrow. The resulting clinical manifestations are bone marrow expansion, increase function of the spleen (splenomegaly) and a chronic hemolytic anemia [6,7].…”

The mechanisms of systemic iron homeostasis and etiology, diagnosis, and treatment of hereditary hemochromatosis

“…Hereditary iron overload disorders such as HH and thalassemia syndromes are very common in the world [148][149][150]. Since the discoveries of HFE and hepcidin as the priming pumps in the research field of iron metabolism, a lot of new knowledge about systemic iron regulation have been provided by numerous investigations worldwide.…”