USMLE – Hemolytic Anemia
Various abnormalities may shorten the normal red cell lifespan of 120 days and anemia develops when marrow output no longer compensates. The increased output of new erythrocytes is reflected in a raised reticulocyte count, which gives an indication of the severity of the process. Normoblasts may be released under extreme stress. The catabolic pathways for hemoglobin degradation are overloaded and there is a modest increase in unconjugated bilirubin in the blood and increased re-absorption of urobilinogen from the gut, which is excreted in the urine in increased amounts. Bilirubin does not appear in the urine. Jaundice is mild.
Hemolysis may occur intravascularly or extravascularly. Hemoglobin liberated into the plasma is bound mainly by the alpha-2 globulin, haptoglobin, to form a complex too large to be lost in the urine. It is taken up by the liver and degraded. Some hemoglobin is partially degraded and bound to albumin to form methemalbumin. If all the haptoglobin has been consumed, free hemoglobin may be lost in the urine. In small amounts this is re-absorbed by the renal tubules, where the hemoglobin is degraded and the iron stored as hemosiderin. Sloughing of the renal tubular cells gives rise to hemosiderinuria which, if found, always indicates intravascular hemolysis. Hemoglobinuria occurs when greater amounts of hemoglobin are lost, giving the urine a black appearance (‘black water’).
Extravascular hemolysis occurs in the phagocytic cells of the spleen, liver, bone marrow and other organs and there may be little or no depletion of haptoglobin. Estimation of the haptoglobin level in the blood is not always easily interpreted. Inflammatory disease and steroid therapy both increase haptoglobin levels. Ahaptoglobinemia may occur as an inherited disorder. Nevertheless, absence of haptoglobin is usually a strong indicator of hemolytic disease. Its presence does not exclude hemolysis.
Blood and marrow findings
The peripheral blood shows a moderate macrocytosis and polychromasia from reticulocytosis, while specific red cell abnormalities may give a clue to the type of hemolytic disease. There may be a polymorphonuclear leucocytosis. The marrow shows erythroid hyperplasia. A megaloblastic change usually reflects depletion of folate reserves. Increased erythropoietic turnover in the marrow is associated with increased serum lactate dehydrogenase levels which, in the absence of folate deficiency, closely follows the severity of the hemolytic disorder. Red cell survival can be measured crudely using radioactive chromium (51-Cr). Surface counting performed at the same time over liver and spleen may give an indication of the site of hemolysis. If transfusion has been given, the patient’s blood will contain a mixed cell population which is not suitable for 51-Cr studies. In these circumstances cross- matched donor cells should be used for labeling.
The causes of hemolytic anemias are classified as congenital or acquired.