Investigation of anemia of unknown origin

One of the most difficult concepts to explain when training immunohematology staff involves the investigation of hemolytic anemias. In the transfusion service and in the immunohematology reference laboratory setting, rapid and efficient investigation can be extremely important for patients with critical anemia requiring transfusion. The flow charts presented here provide possible patient scenarios and a logical sequence for initial and subsequent serologic testing for investigation. A clinical assessment of anemia of unknown origin or the finding of an unresolved positive antibody screen in pre-transfusion patient testing begins the investigational flow process. The testing sequence is predicated on the fact that performing a direct antiglobulin test (DAT) on all patients has a low predictive value and should be reserved for patients with unexplained anemia. The process begins with assessing the results of DATs with anti-IgG and anti-C3. Subsequent charts A, B, and C aid in investigating these results. Flow Chart A is for the investigation of warm or cold autoantibody, Chart B is for the investigation of cold-agglutinin or drug-induced immune hemolytic anemia, and Chart C is for the investigation of autoantibody in the transfused patient. While the most common approaches to the initial and subsequent test results are in these flow charts, the charts are not inclusive of all possible diagnoses or presentations. These flow charts are meant to be a guide to assist the laboratory in developing a standard approach to efficient investigation and resolution in patients with unexplained anemia.