The hemolytic anemias are a group of disorders in which RBC survival is reduced, either episodically or continuously. The bone marrow has the ability to increase erythroid production up to eightfold in response to reduced RBC survival, so anemia will be present only when the ability of the bone marrow to compensate is outstripped. This will occur when RBC survival is extremely short or when the ability of the bone marrow to compensate is impaired.
Since RBC survival is normally 120 days, in the absence of RBC 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 RBC 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 RBC production and earlier release of young RBCs into the circulation. However, hemolysis can be present without reticulocytosis when a confounding erythropoietic disorder (infection, nutritional deficiency, disturbed marrow) 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 consistently low despite reticulocytosis.
Hemolytic disorders are generally classified according to whether the defect is intrinsic to the RBC or due to some external factor (Table 13–8). Intrinsic defects have been described in all components of the RBC, including the membrane, enzyme systems, and hemoglobin; most of these disorders are hereditary. Hemolytic anemias due to external factors are classified as immune, microangiopathic hemolytic anemias, drug-induced, and RBC infections.
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
Immune: autoimmune, lymphoproliferative disease, drug-induced, idiopathic
Microangiopathic: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, disseminated intravascular coagulation, valve hemolysis, metastatic adenocarcinoma, vasculitis, copper overload
Infection: Plasmodium, Clostridium, Borrelia
Certain laboratory features are common to all hemolytic anemias. Haptoglobin, a normal plasma protein that binds and clears free hemoglobin released into plasma, is depressed in hemolytic disorders. However, the haptoglobin level is influenced by many factors and is not always a reliable indicator of hemolysis, particularly in end-stage liver disease (its site of synthesis). When intravascular ...