Positive Direct Antiglobulin Tests in Myeloma Patients: Occurrence, Characterization, and Significance

Abstract

Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis.

Evaluation of the Microcolumn Technology for Pretransfusion Testing in Multiple Myeloma Patients

“…Clark et al [6], however, considered patients with concentration of monoclonal protein from 6.5 to 12.0 g/dl while in our patients the protein concentration was usually below 6.5 g/dl. Dalal et al [20] also observed patients with higher concentration of monoclonal protein than we did. In their material the mean protein concentration in DAT-positive patients (traditional, not gel DAT) was 5.76 and in negative ones 3.57, while in our patients 4.22 and 2.56, respectively.…”

“…Hence, red cells from MM patients were coated with immunoglobulins in a nonspecific way, different from that of antigen/antibody binding. This nonspecific binding of IgG was related to the level of monoclonal protein in the patients’ sera as reported by Clark et al [6] and Dalal et al [20]. Clark et al [6], however, considered patients with concentration of monoclonal protein from 6.5 to 12.0 g/dl while in our patients the protein concentration was usually below 6.5 g/dl.…”

“…In their material the mean protein concentration in DAT-positive patients (traditional, not gel DAT) was 5.76 and in negative ones 3.57, while in our patients 4.22 and 2.56, respectively. In addition the positive tube DAT was in most patients very weak and only transiently observed [20]. Both reports, Clark et al [6] and Dalal et al [20], explain why we have never observed a positive tube DAT.…”

“…In addition the positive tube DAT was in most patients very weak and only transiently observed [20]. Both reports, Clark et al [6] and Dalal et al [20], explain why we have never observed a positive tube DAT. Our negative data are consistent with the ELAT results – in 40 out of 41 patients the number of IgG was below 200.…”

Blood donors with positive direct antiglobulin tests are at increased risk for cancer

“…An increased prevalence of gammopathies is found in lymphoma, hairy cell leukemia, gastric cancer, ovarian cancer, lung cancer, chondrosarcoma, and hepatocellular carcinoma, as well as liver disease and connective tissue diseases 13 . Furthermore, a positive DAT is frequently encountered in patients with multiple myeloma 14 . The reaction is due to passive absorption of the monoclonal protein onto the RBCs and this usually does not produce hemolysis 14 …”