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Etiology of Anemia


Evan M. Braunstein

, MD, PhD, Johns Hopkins School of Medicine

Last full review/revision Sep 2020| Content last modified Sep 2020
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Anemia is a decrease in the number of red blood cells (RBCs), which leads to a decrease in hematocrit and hemoglobin content. (See also Red Blood Cell Production.)

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

Iron utilization defect (inherited sideroblastic anemia)


Anemia of chronic inflammation, infection, or cancer

Kidney disease

Endocrine failure (thyroid, pituitary)



Liver disease

Malabsorption (eg, tropical sprue)


Excessive hemolysis due to extrinsic red blood cell defects

Reticuloendothelial hyperactivity with splenomegaly

Immunologic abnormalities



Ebstein Barr virus (EBV) infection

Mechanical injury

Foot strike hemolysis




Spider bites

Excessive hemolysis due to intrinsic red blood cell defects

Membrane alterations, acquired

Membrane alterations, congenital

Hereditary stomatocytosis

Hereditary xerocytosis


Metabolic disorders (inherited enzyme deficiencies)


Sickle cell disease (Hb S disease)

Thalassemias (beta, beta-delta, and alpha)

* Classified according to red blood cell indices.

Blood loss can 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 white blood cells 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%/week (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 or there is erythropoietin deficiency.

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