Causes of Anemia in Patients

Anemia in patients with lung cancer has a multifactorial etiology (6). Contributing factors are the anemia of chronic disorders, concomitant postobstructive respiratory infections, tumor-induced autoimmune hemolysis, and bone marrow invasion or dysfunction caused by the tumor. These patients can also have iron, folate, or vitamin B12 deficiency, as well as blood loss from tumor erosion.

Endogenous EPO is of particular interest, since anemic cancer patients have been shown to have inappropriately low amounts of circulating EPO for their degree of anemia, reflecting a perturbation in this homeostatic mechanism, with loss of the normally expected inverse linear relation between serum EPO and Hb concentrations (7,8). In a study with a very homogenous group of chemotherapy- and radiotherapy-naive patients with lung cancer, analysis of serum EPO and soluble transferrin receptor suggested that impaired erythroid marrow response to EPO and a relative inadequacy of EPO production were important mechanisms in the chronic anemia of lung cancer (9). Both phenomena are probably owing to the production of inflammatory cytokines such as tumor necrosis factor (TNF) (10).

The EPO response and RBC production is further decreased in cancer patients receiving chemotherapy, both cisplatin-based or other (7). In patients with lung cancer more specifically, erythropoiesis can be greatly affected. Indeed, cisplatin-based chemotherapy is the standard of care for many patients with this disease (11,12). Platinum-based chemotherapy causes anemia not only by the mechanisms listed above, but also by its direct effect on the renal tubules, which leads to a decrease in the production of EPO (13). Patients with locally advanced nonsmall-cell lung cancer (NSCLC) or limited disease small-cell lung cancer (SCLC) will be even more prone to the development of anemia, since state-of-the-art therapy for these patients consists of a combination of platinum-based chemotherapy together with radiation, thereby further increasing the risk of myelosuppression (14,15).

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