Sideroblastic Anemia: Laboratory Evaluation, Diagnostic Challenges, and Clinical Correlation
Abstract
Background: Sideroblastic anemia (SA) is a heterogeneous group of disorders unified by the pathological hallmark of ring sideroblasts—erythroid precursors with perinuclear mitochondrial iron accumulation visible on Prussian blue-stained bone marrow aspirates. This results from defective heme synthesis, leading to ineffective erythropoiesis and a characteristic paradox of systemic iron overload concurrent with anemia.
Aim: This article provides a comprehensive review of the laboratory evaluation, diagnostic challenges, and clinical management of sideroblastic anemia. It aims to delineate the pathophysiologic pathways, categorize the diverse etiologies, and correlate diagnostic findings with appropriate therapeutic strategies.
Methods: A detailed analysis of the etiology, pathophysiology, and histopathology of SA is presented. The diagnostic approach integrates complete blood count, iron studies, peripheral smear for siderocytes, and definitive bone marrow examination. Further classification relies on genetic testing for hereditary forms and molecular analysis (e.g., for SF3B1 mutations) for acquired, clonal variants like myelodysplastic syndromes with ring sideroblasts (MDS-RS).
Results: Management is etiology-driven. Hereditary forms, often involving ALAS2 mutations, may respond to pyridoxine (Vitamin B6). Acquired, reversible causes (e.g., copper deficiency, alcohol, drugs) require removal of the insult. Clonal MDS-RS variants are managed with erythropoiesis-stimulating agents, luspatercept, or hypomethylating agents. Iron overload, a universal complication, necessitates vigilant monitoring and chelation or phlebotomy to prevent end-organ damage.
Conclusion: Accurate diagnosis of SA hinges on marrow morphology and systematic evaluation to distinguish between congenital, acquired, and clonal causes, which is crucial for implementing targeted therapy and managing iron overload to improve patient outcomes.
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Copyright (c) 2024 Majed Abdullah Saleh Alyahya, Sultan Shafi Alanazi, Ahmed Abdulaziz Alblaihi, Rayed Fahad ALhammad, Khudhair Fahad Alharbi, Mohammed Shaliyel D ALotaibi, Khaled Abdullah Saad Almutleb, Hussain Brakh ALharbi, Abdullah Mohammad Alshahrani, Mofareh Mohammad Alshahrani
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