The hemolytic anemias are a group of disorders in which red blood cell survival is reduced, either episodically or continuously. The bone marrow has the ability to increase erythroid production up to eightfold in response to reduced red cell survival, so anemia will be present only when the ability of the bone marrow to compensate is outstripped. This will occur when red cell survival is extremely short or when the ability of the bone marrow to compensate is impaired.
Since red blood cell survival is normally 120 days, in the absence of red cell production, the hematocrit will fall at the rate of approximately 1/120 of the hematocrit per day, which translates to a decrease in the hematocrit reading of approximately 2–3% (absolute percentage) per week. For example, a fall of hematocrit from 45% to 36% over 3 weeks need not indicate hemolysis, since this rate of fall would result simply from cessation of red blood cell production. If the hematocrit is falling at a rate faster than that due to decreased production, blood loss or hemolysis is the cause.
Reticulocytosis is an important clue to the presence of hemolysis, since in most hemolytic disorders the bone marrow will respond with increased red blood cell production and earlier release of young red blood cells into the circulation. However, hemolysis can be present without reticulocytosis when a confounding erythropoietic disorder (infection, nutritional deficiency) is superimposed on hemolysis; in these circumstances, the hematocrit will fall rapidly. Reticulocytosis does not necessarily imply hemolysis, since it also occurs during recovery from hypoproliferative anemia (replacement of a missing nutrient) or acute bleeding. Hemolysis is correctly diagnosed (when acute bleeding and nutrient replacement are excluded) if the hematocrit is either falling or stable despite reticulocytosis.
Hemolytic disorders are generally classified according to whether the defect is intrinsic to the red cell or due to some external factor (Table 13–8). Intrinsic defects have been described in all components of the red blood cell, including the membrane, enzyme systems, and hemoglobin; most of these disorders are hereditary (eFigure 13–20). Hemolytic anemias due to external factors are immune and microangiopathic hemolytic anemias and infections of red blood cells.
Table 13–8.Classification of hemolytic anemias. ||Download (.pdf) Table 13–8. Classification of hemolytic anemias.
Membrane defects: hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria
Glycolytic defects: pyruvate kinase deficiency, severe hypophosphatemia
Oxidation vulnerability: glucose-6-phosphate dehydrogenase deficiency, methemoglobinemia
Hemoglobinopathies: sickle cell syndromes, thalassemia, unstable hemoglobins, methemoglobinemia
Immune: autoimmune, lymphoproliferative disease, drug-induced
Microangiopathic: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, disseminated intravascular coagulation, valve hemolysis, metastatic adenocarcinoma, vasculitis, copper overload
Infection: Plasmodium, Clostridium, Borrelia
Hereditary elliptocytosis. (Peripheral blood, 50 ×.) Many ellipsoid forms in a patient with hereditary elliptocytosis. A congenital membrane abnormality results in abnormal red blood cell deformability and shortened red blood cell survival. The membrane abnormality also results in ...