Anemia of blood loss can be divided into anemia caused by acute bleeding (hemorrhage) and anemia caused by chronic blood loss (described later). The effects of acute bleeding are mainly due to the loss of intravascular volume, which if massive can lead to cardiovascular collapse, shock, and death. If blood loss exceeds 20% of blood volume, the immediate threat is hypovolemic shock rather than anemia. If the patient survives, hemodilution begins at once and achieves its full effect within 2 to 3 days; only then is the full extent of the red cell loss revealed. The anemia is normocytic and normochromic. Recovery from blood loss anemia is enhanced by a compensatory rise in the erythropoietin level, which stimulates increased red cell production and reticulocytosis within a period of 5 to 7 days.
With chronic blood loss, iron stores are gradually depleted. Iron is essential for hemoglobin synthesis and erythropoiesis, and its deficiency leads to a chronic anemia of underproduction. Iron deficiency anemia can occur in other clinical settings as well; it is described later along with other forms of anemia caused by decreased red cell production.
Hemolytic anemias are a diverse group of disorders that have as a common feature accelerated red cell destruction (hemolysis). By definition, the red cell life span is shortened to less than its normal 120 days, often markedly so. Regardless of cause, low tissue O2 levels trigger increased erythropoietin release from the kidney, which in turn stimulates the growth of erythroid elements and increased release of reticulocytes from the bone marrow. Thus, erythroid hyperplasia and reticulocytosis are hallmarks of all hemolytic anemias. In severe hemolytic anemias, the erythropoietic drive may be so pronounced that extramedullary hematopoiesis appears in the liver, spleen, and lymph nodes.
There are several ways to organize hemolytic anemias. One approach groups them according to whether the pathogenic red cell defect is intrinsic (intracorpuscular) or extrinsic (extracorpuscular) (see
Table 12.1 ). A second more clinically useful approach groups hemolytic anemias according to whether hemolysis is primarily extravascular or intravascular. Extravascular hemolysis is caused by defects that increase the destruction of red cells by phagocytes, particularly in the spleen. The spleen contains large numbers of macrophages, the principal cell responsible for the removal of damaged or antibody-coated red cells from the circulation. Because extreme alterations of shape are necessary for red cells to navigate the splenic sinusoids, any reduction in red cell deformability makes this passage difficult, and red cells that become “stuck” are recognized and phagocytosed by resident splenic macrophages. As described later in the chapter, diminished deformability is a major cause of red cell destruction in several hemolytic anemias. Findings that are relatively specific for extravascular hemolysis http://ebooksmedicine.net
Fig. 12.1 Pathogenesis of hereditary spherocytosis. (Left panel) Normal organization of the major red cell membrane skeleton proteins. Mutations in α-spectrin, β-spectrin, ankyrin, band 4.2, and band 3 that weaken the association of the membrane skeleton with the overlying plasma membrane cause red cells to shed membrane vesicles and transform into spherocytes (right panel). The nondeformable spherocytes are trapped in the splenic cords and phagocytosed by macrophages. GP, Glycophorin.
(as compared to intravascular hemolysis) include the following:
Hyperbilirubinemia and jaundice, stemming from degradation of hemoglobin in macrophages