Anemia in cancer

If Anemia is one of the most common complications of malignancy and the treatment of cancer.



Estimated 20-60% of patients with cancer have anemia at the time of diagnosis.


An estimated 26-85% of patients with gynecologic malignancies have anemia.


The percentage of cancer patients who have anemia increases to 60-90% of those doing cancer therapy, and a subset has anemia of cancer that is chemotherapy-induced.


Anemia and cancer is multi factorial: bleeding, nutritional deficiencies, hemolysis , reduced erythropoietin  levels, inflammation with increased hepcidin activity, and toxic effects of chemotherapy on bone marrow precursors.



Anemia of cancer is mediated by cytokines produced by malignancy, such as interferon, tumor necrosis factor, in interleukin, all of which can you suppress erythropoiesis.


Suppression may result from inhibition of iron metabolism and utilization with an increase in the iron regulatory protein hepcidin, which in turn leads to the sequestration of iron in macrophages. 


Systemic inflammation leads to activation of the hepcidin pathway affecting iron metabolism.


Cytokines such as IL-2beta, IL-6 and Lipopolysaccharide induce the production and activation of hepcidin in the liver.


Hepcidin Increases iron retention in macrophages and decreases dietary iron absorption in the duodenum, in both cases by the degradation of ferroportin: these effects cause hypoferremia and hyperferrritinemis making iron less available for erythropoiesis.

Heme is synthesized by protoporhyrin, a byproduct of glucose metabolism.

Iron is involved in the regulation of erythropoietin synthesis in conjunction with hypoxia-inducible factor2A gene.

In cancer related anemia pro inflammatory cytokines such as IL-6 increase the production of hepcidin in the liver, resulting in a decrease in HIF and subsequently erythropoietin. 

A functional iron deficiency leads to a further the decrease in erythropoiesis.

It is suggested that cancer related inflammation shortens RBC survival resulting from increased destruction, suppressed  erythropoiesis due to decreased erythropoietin, suppressed bone marrow erythropoiesis, and iron restricted erythropoiesisdue to an increase in hepcidin.

Cancer related anemia tends to be hypo proliferative, with low reticulocyte index, and normochromic, normocytic indices.

Iron studies demonstrate lowered serum iron and reduced total Iron binding capacity, and ferritin levels can be low or elevated.

EPO levels tend to be low in the setting of anemia of cancer, and addition, the transferrin receptor to ferritin ratio is low.

Anemia induced by the cancer can be from direct effects of the tumor.

Malignancies may cause bleeding by damaging endothelium-G.I. or GU bleeding. 

Tumors May bleed into itself and other malignancies can lead to internal hemorrhage.

Endothelial damage can cause anemia through the initiation of disseminated intravascular coagulation, which occurs through the release of tissue factor, and activator a factor VII that is expressed in tumor cells.

Neoplasms can impede absorption of vital nutrients required for the creation of RBCs.

Malignancies can lead to bone marrow replacement, especially with hematologic malignancies.

Neoplasms byproducts  can be antigenic, leading to immune mediated anemias.

Solid and hematologic malignancies may be associated with microangiopathic hemolytic anemias.

Cancer treatments that include surgery, radiation, chemotherapy, targeting agents, and immunotherapy may impair marrow function and cause anemia.

The treatment for anemia related to an underlying cancer is directed at the lesion.

Erythropoietin stimulating agents (ESA) are approved for use in chemotherapy induced anemia.

The use of ESAs is associated with an increased risk for venous thromboembolism.

Cytokines  decrease the production everythropoietin and by inhibiting messenger RNA synthesis.


Acute blood loss from cytotrdictivr surgery, renal impairment from chemotherapy, and bone marrow impairment from chemotherapy, radiation, or other treatments may also contribute to cancer associated anemia.


Erythropoiesis and erythroid differentiation are impaired in inflammatory states.


Erythropoietin production in kidney is inhibited by IL-1, IFN -gamma, and TNF-alpha.


Patients with cancer and anemia have an increased mobility and mortality: Such patients often present with shortness of breath, lethargy, palpitations, or syncope, and the symptoms of anemia may impair daily function and contribute to decreased quality of life.


Studies have shown an association between anemia and worse response to treatment and survival in a variety of cancers including: ovarian, endometrial, cervical, and vulvar malignancies.


Among gynecologic cancers, anemia is associated with poor local tumor control, potentially related to tumor hypoxia mediated resistance to treatment.


In general,patients with cancer and anemia, should  undergo evaluation for the causes of anemia with hemoglobin of 11 g/dL or less.





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