Causes and Pathophysiology of Acquired Sideroblastic Anemia

Abstract

The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by anemia and the presence of ring sideroblasts in the bone marrow. Ring sideroblasts are abnormal erythroblasts with iron-loaded mitochondria that are visualized by Prussian blue staining as a perinuclear ring of green-blue granules. The mechanisms that lead to the ring sideroblast formation are heterogeneous, but in all of them, there is an abnormal deposition of iron in the mitochondria of erythroblasts. Congenital sideroblastic anemias include nonsyndromic and syndromic disorders. Acquired sideroblastic anemias include conditions that range from clonal disorders (myeloid neoplasms as myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms with ring sideroblasts) to toxic or metabolic reversible sideroblastic anemia. In the last 30 years, due to the advances in genomic techniques, a deep knowledge of the pathophysiological mechanisms has been accomplished and the bases for possible targeted treatments have been established. The distinction between the different forms of sideroblastic anemia is based on the study of the characteristics of the anemia, age of diagnosis, clinical manifestations, and the performance of laboratory analysis involving genetic testing in many cases. This review focuses on the differential diagnosis of acquired disorders associated with ring sideroblasts.

Dolutegravir‐induced acquired sideroblastic anemia in a HIV positive patient: A challenging hematologic complication

“…Sideroblastic anemias include a heterogeneous group of inherited/congenital and acquired disorders characterized by ineffective erythropoiesis and the presence of ring sideroblasts in the bone marrow aspirate. Ring sideroblasts, aberrant erythroblasts with iron‐loaded mitochondria, are seen as a perinuclear ring of green‐blue granules when stained with Prussian blue 2 . There should be a minimum of five granules encircling one‐third of the nuclear diameter in this Prussian blue staining process known as the Perls reaction 11 .…”

“…Ring sideroblasts, aberrant erythroblasts with iron‐loaded mitochondria, are seen as a perinuclear ring of green‐blue granules when stained with Prussian blue. 2 There should be a minimum of five granules encircling one‐third of the nuclear diameter in this Prussian blue staining process known as the Perls reaction. 11 Sideroblastic anemias can be grouped into inherited and acquired forms.…”

“…This leads to the formation of ring sideroblasts, where iron‐laden mitochondria surround the nuclei of erythroblasts 1 . Ring sideroblasts can be present in various pathological conditions, including both congenital and acquired forms of sideroblastic anemias 2 . The underlying mechanisms leading to different forms of sideroblastic anemias are diverse.…”

“… 1 Ring sideroblasts can be present in various pathological conditions, including both congenital and acquired forms of sideroblastic anemias. 2 The underlying mechanisms leading to different forms of sideroblastic anemias are diverse. However, in all cases, the abnormal accumulation of iron is attributed to disruptions in mitochondrial proteins involved in regulating heme synthesis or Fe/S cluster synthesis.…”

Dolutegravir-induced severe sideroblastic anemia

“…In the Philippines, sexual minorities face minority stress due to stigma and discrimination related to HIV, sexual orientation, and drug use, particularly in the context of ''chemsex'' [4,8]. Societal prejudices against sexual minority identities and drug use force individuals to conceal their identities and HIV status, amplifying mental health risks [2,4,9,10]. Additionally, negative attitudes toward drug use, notably crystal methamphetamine, heighten shame and fear among sexual minorities, further impeding healthcare access [2,11,12].…”