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Etiology of Anemia

By Evan M. Braunstein, MD, PhD, Assistant Professor of Medicine, Division of Hematology, Department of Medicine, Johns Hopkins School of Medicine

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Anemia is a decrease in the number of RBCs, hematocrit (Hct), or hemoglobin (Hb) content.

The RBC mass represents the balance between production and destruction or loss of RBCs. Thus, anemia can result from one or more of 3 basic mechanisms (see Table: Classification of Anemia by Cause):

Classification of Anemia by Cause



Blood loss






Cancer or polyps in GI tract

Kidney tumors

Ulcers in the stomach or small intestine

Deficient erythropoiesis*


Iron reutilization defect (anemia of chronic inflammation, infection, cancer)

Iron-transport deficiency (iron refractory iron deficiency anemia [IRIDA])

Iron utilization defect (inherited sideroblastic anemia)

Thalassemias (also classified under excessive hemolysis due to intrinsic RBC defects)


Anemia of chronic inflammation, infection, or cancer

Kidney disease

Endocrine failure (thyroid, pituitary)



Liver disease

Malabsorption (eg, tropical sprue)


Excessive hemolysis due to extrinsic RBC defects

Reticuloendothelial hyperactivity with splenomegaly

Immunologic abnormalities



Ebstein Barr virus (EBV) infection

Mechanical injury

Cardiac valvular disease

Foot strike hemolysis




Spider bites

Excessive hemolysis due to intrinsic RBC defects

Membrane alterations, acquired

Membrane alterations, congenital

Metabolic disorders (inherited enzyme deficiencies)


Thalassemias (beta, beta-delta, and alpha)

*Classified according to RBC indices.

Blood losscan be acute or chronic. Anemia does not develop until several hours after acute blood loss, when interstitial fluid diffuses into the intravascular space and dilutes the remaining RBC mass. During the first few hours, however, levels of polymorphonuclear granulocytes, platelets, and, in severe hemorrhage, immature WBCs and normoblasts may rise. Chronic blood loss results in anemia if loss is more rapid than can be replaced or, more commonly, if accelerated erythropoiesis depletes body iron stores (see Iron Deficiency Anemia).

Deficient erythropoiesis has myriad causes. Complete cessation of erythropoiesis results in a decline in RBCs of about 7 to 10%/wk (1%/day). Impaired erythropoiesis, even if not sufficient to decrease the numbers of RBCs, often causes abnormal RBC size and shape.

Excessive hemolysis can be caused by intrinsic abnormalities of RBCs or by extrinsic factors, such as the presence of antibodies or complement on their surface, that lead to their early destruction. An enlarged spleen sequesters and destroys RBCs more rapidly than normal. Some causes of hemolysis deform as well as destroy RBCs. Hemolysis normally causes increased reticulocyte production unless iron or other essential nutrients are depleted.

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