A second form of acquired hemolytic disease is caused by mechanical damage to the RBC membrane during circulation. In thrombotic microangiopathy, the RBCs are trapped by fibrin strands in the circulation and physically broken by shear stress as they pass through these strands. Hemolytic uremic syndrome, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, malignant hypertension, toxemia, and hyperacute renal graft rejection can produce thrombotic microangiopathy. The platelets are usually large, indicating that they are young, but have a decreased survival even if the numbers are normal. Consumption of clotting factors is more prominent in DIC than in the other forms of thrombotic microangiopathy. The smear shows RBC fragments (schistocytes), microspherocytes, teardrop forms, and polychromasia. Other examples of mechanical injury to RBCs include damage by exposure to nonendothelialized surfaces (as in artificial heart valves) or as a result of high flow and shear rates in giant hemangiomas (Kasabach-Merritt syndrome).
Alterations in the plasma lipids, especially cholesterol, may lead to damage to the RBC membrane and shorten RBC survival. Lipids in the plasma are in equilibrium with lipids in the RBC membrane. High cholesterol levels increase the membrane cholesterol and the total membrane surface without affecting the volume of the cell. This condition produces spur cells that may be seen in abetalipoproteinemia and liver diseases. Hemolysis occurs in the spleen, where poor RBC deformability results in erythrocyte destruction. Circulating toxins (e.g., snake venoms and heavy metals) that bind sulfhydryl groups may damage the RBC membrane and induce hemolysis. Irregularly spiculated RBCs (burr cells) are seen in renal failure. Vitamin E deficiency can also cause an acquired hemolytic anemia as a result of abnormal sensitivity of membrane lipids to oxidant stress. Vitamin E deficiency may occur in premature infants who are not being supplemented with vitamin E or who have insufficient nutrition, in infants with severe malabsorption syndromes (including cystic fibrosis), and in infants with transfusional iron overload, which can lead to severe oxidant exposure.
Laboratory Diagnosis. The peripheral blood smear in autoimmune hemolytic anemia usually reveals spherocytes and occasionally nucleated RBCs. The reticulocyte count varies because some patients have relatively low reticulocyte counts as a result of autoantibodies that cross-react with RBC precursors.
Treatment and Prognosis. Transfusion for the treatment of autoimmune hemolysis is challenging because crossmatching is difficult, as the autoantibodies react with virtually all RBCs. In addition to transfusion, which may be lifesaving, management of autoimmune hemolytic anemia depends on antibody type. Management may involve administration of corticosteroids and, at times, intravenous immunoglobulin. Corticosteroids reduce the clearance of sensitized RBCs in the spleen. In drug-induced hemolysis, withdrawal of the drug usually leads to resolution of the hemolytic process. More than 80% of children with autoimmune hemolytic anemia recover spontaneously.