Anemia in malignancies: pathogenetic and diagnostic considerations

The aim of this paper is to review the pathogenesis and diagnostic approaches to anemia in cancer patients.

PubMed was queried for various combinations of anemia and cancer-related terms using appropriate filters for articles and practice guidelines published in the last 5 years. Specific searches were conducted for individual pathogenetic mechanisms and malignancies of specific anatomic sites.

Anemia is the commonest hematological manifestation of cancer, afflicting 40-64% of patients treated for malignancies. Pathophysiologically, cancer-related anemia can be classified into four broad but overlapping categories: hypoproliferative anemia including the common anemia of inflammation/chronic disease, hemolytic anemia, miscellaneous etiologies, and uncertain etiologies. Anemia incidence increases with the administration of chemotherapy/radiotherapy. It reduces the quality of life and shortens survival in cancer patients. A positive correlation is observed between anemia and tumor hypoxia. Experimentally, hypoxemia enhances tumor growth and resistance to therapy by stimulating angiogenesis, acquisition of genomic mutations, and increasing resistance to apoptosis as well as to the killing effects of chemo/radiotherapy-generated free radicals.

Diagnostic approaches to the anemic cancer patient begin with a detailed clinical history and physical examination. Peripheral blood morphology and reticulocyte count are also helpful. Patients with unexplained anemia are evaluated by standard approaches also used in patients of similar age without malignancy. Serum iron profile and bone marrow examination are often required in difficult cases. This review focuses on major aspects of the pathogenesis of the individual entities. Diagnostic approaches and uncommon causes including hemophagocytic lymphohistiocytosis, acquired hemoglobinopathies, and myelodysplasia are also discussed.