Laboratory Evaluation Of Hemolytic Anemia

1. Complete blood count (CBC). The anemia that occurs may be mild or severe; verify normal/abnormal white blood cell count and platelet count.

2. Reticulocyte count. This is the single most useful test in ascertaining the presence of hemolysis and a normal bone marrow response; this should be elevated and can be as high as 30 to 40 percent.

3. Review of the peripheral blood smear. Most hemolytic disorders are associated with changes in the morphology of the red blood cells (RBCs); typical changes may include a. Spherocytes. These are the most common morphologic abnormality in hemolytic diseases; they will be most abundant in patients with warm antibody immune hemolysis and those with hereditary spherocytosis (Chap...213).

b. Schistocytes. These are fragmented RBCs that result from direct trauma within the vasculature, most often in the microvasculature (known as microangiopathic hemolytic anemia, MAHA), but also can occur in the macrovasculature; schistocytes are markers of nonimmune hemolysis.

4. Unconjugated (indirect) bilirubin. This should be elevated in the presence of hemolysis as a result of heme catabolism; the direct (conjugated) bilirubin should be normal unless there is concomitant hepatic or biliary dysfunction.

5. Haptoglobin. This binds to the protein globin that is released when hemoglobin is catabolized, so this should be low or absent in the presence of significant hemolysis. Haptoglobin is an acute-phase reactant that may be increased in conditions such as severe infection, tissue destruction, myocardial infarction, and burns and in some cancer patients; in these settings, the haptoglobin level may be increased, despite the presence of hemolytic anemia.

6. Plasma free hemoglobin. This should be elevated in hemolysis.

7. Lactic dehydrogenase (LDH). This should be elevated in hemolysis; it can be a relatively sensitive marker used to follow the course of a hemolytic disease. AUTOIMMUNE HEMOLYTIC ANEMIAS

There are three types of antibody-mediated, so-called immune, hemolytic anemias:

1. Warm antibody hemolytic anemia. These antibodies are reactive at body temperature.

2. Cold antibody hemolytic anemia. These antibodies react with the patient's RBCs at temperatures below normal body temperature.

3. Drug-induced immune hemolytic anemia. Certain drugs can cause an immune reaction in some patients that results in destruction of their RBCs.

Immune hemolytic anemias are characterized in the laboratory by the Coombs antiglobulin test, also known as the direct Coombs' test or direct antiglobulin test (DAT). This test demonstrates the presence of immunoglobulin (IgG) or complement (C3) on the surface of the RBC. It is only positive in immune-mediated hemolytic anemias. The indirect Coombs' test is used primarily for pretransfusion screening for antibodies; it demonstrates the presence of free antibodies in the patient's serum. Immune hemolysis is typified by abundant spherocytes on the peripheral blood smear.

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