Anemia is a decrease in the number of RBCs, Hct, or 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 1: Approach to the Patient With Anemia: Classification of Anemia by Cause):

• Blood loss
• Deficient erythropoiesis
• Excessive hemolysis (RBC destruction)

Table 1
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Classification of Anemia by Cause Mechanism Examples Blood loss Acute GI bleeding Injuries Childbirth Surgery Chronic Bladder tumors Cancer or polyps in GI tract Heavy menstrual bleeding Kidney tumors Ulcers in the stomach or small intestine Deficient erythropoiesis* Microcytic Iron deficiency Iron-transport deficiency Iron utilization defect Iron reutilization defect Thalassemias (also classified under excessive hemolysis due to intrinsic RBC defects) Normochromic-normocytic Aplastic anemia Hypoproliferation In kidney disease In endocrine failure (thyroid, pituitary) In protein depletion Myelodysplasia Myelophthisis Macrocytic Copper deficiency Folate deficiency Vitamin B12 deficiency Vitamin C deficiency Excessive hemolysis due to extrinsic RBC defects Reticuloendothelial hyperactivity with splenomegaly Hypersplenism Immunologic abnormalities Autoimmune hemolysis Cold antibody hemolysis (paroxysmal cold hemoglobinuria) Warm antibody hemolysis Isoimmune (isoagglutinin) hemolysis Mechanical injury Infection Trauma Excessive hemolysis due to intrinsic RBC defects Membrane alterations, acquired Hypophosphatemia Paroxysmal nocturnal hemoglobinuria Stomatocytosis Membrane alterations, congenital Hereditary elliptocytosis Hereditary spherocytosis Metabolic disorders (inherited enzyme deficiencies) Embden-Meyerhof pathway defects G6PD deficiency Hemoglobinopathies Hb C disease Hb E disease Hb S-C disease Hb S–β-thalassemia disease Sickle cell disease (Hb S) Thalassemias (β, β-δ, and α) *Classified according to RBC indices. Classification of Anemia by Cause Mechanism Examples Blood loss Acute GI bleeding Injuries Childbirth Surgery Chronic Bladder tumors Cancer or polyps in GI tract Heavy menstrual bleeding Kidney tumors Ulcers in the stomach or small intestine Deficient erythropoiesis* Microcytic Iron deficiency Iron-transport deficiency Iron utilization defect Iron reutilization defect Thalassemias (also classified under excessive hemolysis due to intrinsic RBC defects) Normochromic-normocytic Aplastic anemia Hypoproliferation In kidney disease In endocrine failure (thyroid, pituitary) In protein depletion Myelodysplasia Myelophthisis Macrocytic Copper deficiency Folate deficiency Vitamin B12 deficiency Vitamin C deficiency Excessive hemolysis due to extrinsic RBC defects Reticuloendothelial hyperactivity with splenomegaly Hypersplenism Immunologic abnormalities Autoimmune hemolysis Cold antibody hemolysis (paroxysmal cold hemoglobinuria) Warm antibody hemolysis Isoimmune (isoagglutinin) hemolysis Mechanical injury Infection Trauma Excessive hemolysis due to intrinsic RBC defects Membrane alterations, acquired Hypophosphatemia Paroxysmal nocturnal hemoglobinuria Stomatocytosis Membrane alterations, congenital Hereditary elliptocytosis Hereditary spherocytosis Metabolic disorders (inherited enzyme deficiencies) Embden-Meyerhof pathway defects G6PD deficiency Hemoglobinopathies Hb C disease Hb E disease Hb S-C disease Hb S–β-thalassemia disease Sickle cell disease (Hb S) Thalassemias (β, β-δ, and α) *Classified according to RBC 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 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 Anemias Caused by Deficient Erythropoiesis: Iron Deficiency Anemia).

Deficient erythropoiesis (see Anemias Caused by 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 (see Anemias Caused by Hemolysis) can be caused by intrinsic abnormalities of RBCs or by extrinsic factors, such as the presence of antibodies 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. Excessive hemolysis does not normally decrease reticulocyte production unless iron or other essential nutrients are depleted.

Last full review/revision June 2008 by Alan E. Lichtin, MD