We often see anemic patients in the clinic, and one of the important differentials in adults is autoimmune hemolytic anemia. In this video, from our Transfusion Medicine Essentials course, you’ll discover the lab findings that will help you to diagnose this condition and the tests you can use to differentiate hemolytic anemia caused by autoimmune responses and anemia that stems from other causes.
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[00:00:00] We often see patients with anemia in our clinical routine. They present with symptoms such as paleness, fatigue or tachycardia. If the anemia is only mild, there might be no specific symptoms at all. One of the differentials that is common in adults is hemolytic anemia. So what lab findings can help you diagnose hemolysis? If hemolysis is present, you'll find elevated LDH,
[00:00:30] elevated bilirubin, reticulocytosis, a decrease in haptoglobin, and if intravascular hemolysis is present, you should see a significant elevation of free hemoglobin and hemoglobinuria. Once you see a laboratory finding suggesting hemolytic anemia, you should immediately consider the most common cause of hemolytic anemia in adults, autoimmune hemolytic anemia. So what happens in autoimmune hemolysis?
[00:01:00] Basically, antibodies that are directed against individual's own red blood cell antigens, so-called autoantibodies attack the RBCs and cause them to burst. The loss of functional red blood cells leads to anemia. These autoantibodies can be of different immunoglobulin classes IgG, IgM or IgA in some cases. The complement system is also activated. Why some individual's immune systems attack their own cells is not entirely
[00:01:30] understood. 50% of all cases of autoimmune hemolysis are idiopathic so we just don't know why they happen. The other 50% result from secondary causes. Diseases or conditions that are known to induce autoimmune hemolysis include neoplasms, especially lymphoproliferative disorders like lymphoma or chronic lymphocytic leukemia but also other neoplasms; autoimmune diseases like systemic lupus, rheumatoid arthritis,
[00:02:00] inflammatory bowel diseases, and others; infections by mycoplasma, viral pneumonia or infectious mononucleosis or drugs like penicillin, diclofenac or methyldopa. So, how can I verify that the hemolysis I see is autoimmune? To determine whether the hemolysis is autoimmune in nature, the transfusion lab performs the direct antiglobulin test, DAT for short. To perform this test, you need the patient's RBCs
[00:02:30] and antibodies to bind to IgG antibodies, which are known as antiglobulin antibodies or Coombs serum. Basically, we want to verify that the patient’s red blood cells have already been attacked by antibodies that cause hemolysis. In order to do this, you mix the patient's RBCs with the antiglobulin antibodies and incubate them. If the patient's RBCs are covered with IgG antibodies, the antiglobulin antibodies will bind to the IgGs on the RBC surface
[00:03:00] and agglutinate the RBCs. Agglutination can be seen microscopically. In this case, the direct antiglobulin test is positive. You are dealing with autoimmune hemolysis. The lab can go on to determine the specificity of the autoantibodies and whether the complement pathway is activated. These results, plus a proper medical history, help to narrow down the cause of the autoimmune process and lead the way to the best treatment option. If there are no autoantibodies on
[00:03:30] the patient's RBCs, the antiglobulin serum has nothing to bind to so there will be no agglutination. The DAT is negative. There must be a non-autoimmune reason for hemolysis so keep on searching for differentials. So does a positive DAT always indicate an autoimmune process? The answer is no. A positive DAT will not only indicate autoimmune hemolytic disease but also recent hemolysis caused by the incompatibility of red blood cell antigens
[00:04:00] and antibodies. There are two possible reasons for the latter, hemolytic transfusion reaction following incompatible blood transfusion and hemolytic disease of the newborn. In these two cases, RBCs might be covered with IgG antibodies as well. However, these would be alloantibodies instead of autoantibodies. The DAT will induce agglutination of discovered RBCs just the same. So in these situations, the DAT helps you to show that hemolysis is taking place right now.
[00:04:30] Autoimmune hemolytic anemia is an important differential in the workup of anemia. The direct antiglobulin test is a fast and cheap test to help you diagnose it. Furthermore, it can help you determine how recent hemolytic processes are in situations of blood group incompatibilities like after an incompatible transfusion or newborns affected with hemolytic disease of the fetus and newborn.