- Last Update On : 2015-05-04
Autoimmune hemolytic anemias (AIHA) are caused by autoantibodies directed against a patient’s own red blood cells that result in accelerated red cell destruction. This disorder is relatively uncommon, with an incidence of 1 in 80,000 individuals. All ages are affected, with the peak incidence occurring in the fourth and fifth decades. Women are more often affected then men.
AIHA are divided into warm and cold autoantibody types based on the temperatures at which the antibodies maximally react with red blood cells in vitro. Warm autoantibodies are more reactive at 37ºC than at lower temperatures, whereas cold autoantibodies react optimally at 5ºC and less strongly at higher temperatures. These two principal types are further subdivided into primary, or idiopathic, and secondary forms which are associated with an underlying disease. Lymphoproliferative disorders are present in about half of the secondary warm and cold AIHA. Systemic lupus erythematosis and other autoimmune diseases account for the majority of the remaining warm types. Transient cold AIHA are associated with infections, especially mycoplasma pneumonia and infectious mononucleosis.
The clinical picture of warm type AIHA is highly variable. Most patients seek treatment for symptoms attributable to anemia, but occasionally massive hemolysis is seen at onset. Physical findings are related to the degree of anemia and include pallor, resting tachycardia, mild jaundice and occasionally fever. The spleen is usually only mildly enlarged.
Several common laboratory results suggest hemolysis. Hemoglobin is decreased, but the degree of anemia depends on the compensatory capacity of the bone marrow. Reticulocyte count is usually elevated and may result in a mildly elevated MCV. Spherocytes in the peripheral blood smear indicate ongoing red cell destruction. Unconjugated bilirubin is usually, but not always, elevated and urine urobilinogen is increased. Lactate dehydrogenase is usually elevated into the thousands. Serum haptoglobin levels are reduced or undetectable. Hemoglobinemia and hemoglobinuria are present in cases of severe hemolysis. Mild leukocytosis and thrombocytosis may be present.
The diagnosis of AIHA depends on the demonstration of a positive direct antiglobulin test (DAT), indicating the presence of immunoglobulin and/or complement on red blood cells. In warm autoimmune hemolytic anemia, red cells may be coated with IgG, IgG and complement, or complement alone. In warm AIHA, IgG is found alone in about 60% of cases and in association with complement in about 30% of cases. In contrast, cold autoimmune hemolytic anemia is caused by complement-fixing IgM antibodies that react more strongly in the cold than at higher temperatures. In these cases, the direct antiglobulin test detects only complement. Autoantibodies may appear to have specificity for a particular blood group antigen even though the patients’ red cells express that antigen.
The strength of the DAT does not predict the severity of disease. For instance, some patients with a strongly positive DAT have little hemolysis, while other patients with a weakly positive DAT hemolyze extensively. Also, the strength of the DAT often does not change following treatment, even though the clinical condition greatly improves.
Transfusion of patients with autoimmune hemolytic anemia is associated with unique risks. Autoantibody often complicates compatibility testing and makes it difficult to exclude the presence of co-existing alloantibodies, thus increasing the risk of a hemolytic transfusion reaction. Approximately 30% of patients with AIHA have detectable alloantibodies. Undetected alloantibodies may cause increased hemolysis following transfusion, which may be mistakenly attributed to an increase in the severity of AIHA. In patients with severe hemolytic anemia, time may be too short to rule out alloantibodies prior to transfusion. In these situations, it is important to remember that alloantibodies typically cause delayed serologic or hemolytic reactions and should be regarded as a tolerable risk in any patient likely to die from rapidly worsening hemolytic anemia.
The autoantibody itself may shorten the survival of transfused red cells. If possible, red blood cell transfusion should be avoided. However, a patient with life threatening anemia should never be denied blood even though the crossmatch is incompatible. If the hemoglobin level is above 8 g/dL, transfusion is rarely necessary or desirable. A hemoglobin of less than 7 g/dL, which would be considered an acceptable threshold for transfusion in many other groups of patients, may not be appropriate in AIHA patients. Signs of anemia, such as tachycardia, shortness of breath and exercise intolerance should be addressed through other modalities such as absolute bed rest and oxygen therapy, before transfusion is given. Rapidly progressive anemia, cardiac failure and onset of confusion are all appropriate indications for transfusion of patients with AIHA. When the hemoglobin falls below 5 g/dL, most patients will require transfusion.
Warm autoantibodies may demonstrate relative specificity, especially for Rh antigens. Some laboratories select those ABO compatible RBC units that react least strongly with the patient’s autoantibody for transfusion. This practice of selecting “least incompatible” units of RBCs has never been proven to provide clinical benefit and should be abandoned because it only delays transfusion. Unusual cases of warm AIHA may react more strongly with a specific antigen, such as Rh e. Insufficient data is available to determine whether providing antigen negative blood in these cases will lessen the risk of alloimmunization or improve red cell survival.
A critical aspect of transfusing patients with AIHA is to avoid over- transfusion. The kinetics of red cell destruction always describe an exponential decay curve, indicating that the number of cells removed during a unit of time is a percentage of the number of cells present at the start of this time interval. Raising the hemoglobin level abruptly is likely to increase the amount of hemolysis that is occurring and may precipitate DIC. Indeed, the most common cause of post transfusion hemoglobinemia and hemoglobinuria in AIHA may not be alloantibody induced hemolysis but rather the quantitative effect of increasing the red cell mass subjected to ongoing autoantibody hemolysis. Accordingly, transfusion of comparatively small volumes of blood is the optimal means of minimizing the danger of transfusion-induced intravascular hemolysis. The patient's hemoglobin level should be maintained just above a tolerable level until more specific therapy becomes effective.