According to the World Health Organization criteria, anemia is defined as blood hemoglobin (Hb) concentration <130 g/L (<13 g/dL) or hematocrit (Hct) <39% in adult males; Hb <120 g/L (<12 g/dL) or Hct <37% in adult females.

Signs and symptoms of anemia are varied, depending on the level of anemia and the time course over which it developed. Acute anemia is nearly always due to blood loss or hemolysis. In acute blood loss, hypovolemia dominates the clinical picture; hypotension and decreased organ perfusion are the main issues. Symptoms associated with more chronic onset vary with the age of the pt and the adequacy of blood supply to critical organs. Moderate anemia is associated with fatigue, loss of stamina, breathlessness, and tachycardia. The pt's skin and mucous membranes may appear pale. If the palmar creases are lighter in color than the surrounding skin with the fingers extended, Hb level is often <80 g/L (8 g/dL). In pts with coronary artery disease, anginal episodes may appear or increase in frequency and severity. In pts with carotid artery disease, light-headedness or dizziness may develop.

A physiologic approach to anemia diagnosis is based on the understanding that a decrease in circulating RBCs can be related to either inadequate production of RBCs or increased RBC destruction or loss. Within the category of inadequate production, erythropoiesis can be either ineffective, due to an erythrocyte maturation defect (which usually results in RBCs that are too small or too large), or hypoproliferative (which usually results in RBCs of normal size, but too few of them).

Basic evaluations include (1) reticulocyte index (RI), and (2) review of blood smear and RBC indices (chiefly mean corpuscular volume [MCV]) (Fig. 47-1. The Physiologic Classification of Anemia).

The RI is a measure of RBC production. The reticulocyte count is corrected for the Hct level and for early release of marrow reticulocytes into the circulation, which leads to an increase in the lifespan of the circulating reticulocyte beyond the usual 1 day. Thus, RI = (% reticulocytes × pt Hct/45%) × (1/shift correction factor). The shift correction factor varies with the Hct: 1.5 for Hct = 35%, 2 for Hct = 25%, 2.5 for Hct = 15%. RI <2-2.5% implies inadequate RBC production for the particular level of anemia; RI >2.5% implies excessive RBC destruction or loss. About 75% of anemias are hypoproliferative.

If the anemia is associated with a low RI, RBC morphology helps distinguish a maturation disorder from hypoproliferative marrow states. Cytoplasmic maturation defects such as iron deficiency or Hb synthesis problems produce smaller RBCs, MCV <80; nuclear maturation defects such as B₁₂ and folate deficiency and drug effects produce larger RBCs, MCV >100. In hypoproliferative marrow states, RBCs are generally normal in morphology but too few are produced. Bone marrow examination is often helpful in the evaluation of anemia but is done most frequently to diagnose hypoproliferative marrow states.

Other laboratory tests indicated to evaluate particular forms of anemia depend on the initial classification based on the pathophysiology of the defect. These are discussed in more detail in Chap. 63 Red Blood Cell Disorders.