In the latest Case Record of the Massachusetts General Hospital, a 38-year-old woman was admitted to this hospital because of fatigue, malaise, and lightheadedness, with dyspnea on exertion, bruising, dark urine, and headache. Laboratory tests revealed anemia and thrombocytopenia. Diagnostic tests were performed.
Hemolytic anemia associated with normal red cells can be caused by destruction of red cells by antibodies or complement, the shearing of red cells in the microvasculature or by prosthetic heart valves, and infections of red cells. Abnormal red cells may break down because of problems with their hemoglobin, metabolic machinery, or cell membranes, and disorders associated with abnormal red cells are nearly all inherited.
• How does intravascular hemolysis differ from extravascular hemolysis?
Hemolysis may occur within the blood vessels or outside the blood vessels (in the liver, spleen, or bone marrow). During intravascular hemolysis, hemoglobin is released into the blood, binding to haptoglobin and reducing haptoglobin levels, and unbound alpha-globin dimers and beta-globin dimers cause both plasma and urine to turn reddish-brown. As compared with the uncontrolled lysis of red cells that occurs during intravascular hemolysis, extravascular hemolysis is a more controlled process that involves phagocytosis of red cells by macrophages, the breakdown of hemoglobin to bilirubin, and the release of unconjugated bilirubin, iron, and carbon monoxide into the blood.
• What laboratory findings and associated conditions are typically seen in autoimmune hemolytic anemia?
In the setting of laboratory evidence of hemolysis, positive direct antiglobulin test, the presence of spherocytes on the peripheral-blood smear, and normal results on coagulation tests are findings consistent with autoimmune hemolytic anemia. Autoimmune hemolytic anemia can be idiopathic or associated with connective-tissue disease (especially systemic lupus erythematosus [SLE]), viral infection, drug use (especially the use of cephalosporin and piperacillin), malignant diseases (especially chronic lymphocytic leukemia), immunodeficiency (e.g., common variable immunodeficiency), or a previous transfusion or transplantation.
Morning Report Questions
Q: What is Evans syndrome, and what is the first-line treatment?
A: Patients with autoimmune hemolytic anemia and immune thrombocytopenic purpura, neutropenia, or both were described by Evans and Duane in 1949 and by Evans et al. in 1951. The Evans syndrome can be primary (i.e., idiopathic) or associated with SLE or other immune disorders, immunodeficiencies, or lymphoproliferative disorders. In a 2009 review of 68 cases, half of the cases were primary, and many of the secondary cases were associated with SLE. The authors indicate that there are no randomized clinical trials showing the effectiveness of glucocorticoids in the treatment of Evans syndrome, but glucocorticoids have remained the standard treatment option since they were first described for this indication by Dameshek et al. in the Journal in 1950. Prednisone is usually administered (at a dose of 1 to 2 mg per kilogram of body weight per day) until the hematocrit is higher than 30% or the hemoglobin level is higher than 10 g per deciliter; then, prednisone is tapered at a rate of 10 mg per week, as long as the hematocrit and hemoglobin level are stable, to a dose of 20 mg per day. The main goal is to slowly taper the medication over several months and eventually discontinue it. If the hematocrit is still below 30% after 1 month, the initiation of second-line therapy is generally indicated.
Q: How do warm-reacting autoantibodies differ from cold-reacting autoantibodies?
A: Warm-reacting autoantibodies are optimally reactive at 37 degrees C; they usually bind protein antigens and may be associated with hemolysis. In contrast, cold-reacting autoantibodies are optimally reactive at 0 to 4 degrees C; they usually bind carbohydrate antigens and are very rarely associated with hemolysis. Cold-reacting autoantibodies associated with hemolytic anemia usually have a broad thermal range that enables them to bind target antigens at near-physiologic temperatures.