After studying this chapter you should be able to:
Explain the mechanisms underlying antibody-mediated autoimmune hemolysis.
Understand the causes of immune hemolytic anemia as well as its diagnosis and treatment.
Describe the pathogenesis and clinical features of disorders that cause traumatic hemolysis.
Hemolytic anemias are encountered less often than anemias due to decreased red cell production or blood loss. By far the most common hemolytic anemia in both pediatric and adult medicine is sickle cell disease (Chapter 9). Next in prevalence are acquired hemolytic anemias. Familiarity with the pathophysiology of this group of disorders is essential because these patients often pose formidable challenges in both diagnosis and management.
An overview of the hemolytic anemias is presented in Chapter 3 and summarized in Table 3-2. As indicated in Table 11-1, with the exception of the rare disorder paroxysmal nocturnal hemoglobinuria, all of the acquired hemolytic anemias are extracorpuscular. This means that red cells from a compatible donor are hemolyzed as readily as the patient's own red cells. Acquired hemolysis is most often caused by immune-mediated destruction or traumatic mechanical damage of red cells.
TABLE 11-1Acquired Hemolytic Anemias
Immune hemolysis can be triggered by:
This chapter will deal with autoimmune hemolytic anemia. Alloimmune hemolysis will be covered in Chapter 25 (Transfusion Medicine).
Autoimmune hemolytic anemia is conveniently divided into two categories based on the temperature dependence of autoantibody binding to red cells, summarized in Table 11-2.
TABLE 11-2Hemolytic Autoantibodies |Favorite Table|Download (.pdf) TABLE 11-2 Hemolytic Autoantibodies
| ||Warm ||Cold |
|Autoantibody ||IgG ||IgM |
|Specificity ||Rh complex ||I antigen |
|I0 site of clearance ||Spleen ||Liver |
|Mode of recognition ||Common IgG H chain ||C3 |
|Blood film ||Spherocytes ||Agglutination |
Warm autoantibodies bind avidly to the patient's red cells at body temperature. They are immunoglobulin G (IgG) antibodies with specificity for Rh group antigens found on red cells of nearly all individuals. IgG-coated red cells are cleared primarily in the spleen, where they are engulfed by resident macrophages that have receptors for the constant region (Fc) of the heavy (H) chain of IgG. Figure 11-1A shows a macrophage from a patient with warm antibody hemolytic anemia that has just ingested two red cells and is about to destroy them. Alternatively, the patient's IgG-coated red cells may bind to the surface of the macrophage but escape total engulfment. Under these circumstances, the macrophage nibbles at the red cell membrane and removes a small portion of it. ...