Introduction. Wr^a is an antigen of the Diego blood group system. Anti-Wr^a antibody can be found in the sera of healthy individuals (naturally occurring anti-Wr^a) or can be immunostimulated after transfusion or after exposure to foreign erythrocytes during pregnancy. Commercial antibody identification panels do not routinely contain Wr^a antigen-positive erythrocytes. We present two cases of patient blood management in complex situations, such as antibody appearance to low-frequency Wr^a antigen. Case report. In the first presented patient, who received multiple blood transfusions, anti-Wr^a antibody was detected while solving cross-match incompatibility. In the second patient, anti-Wr^a antibody was identified during routine antierythrocyte antibody screening during pregnancy. Immunohematological testing included blood typing and antibody screening, cross-matching, antibody identification, indirect antiglobulin test (IAT), and direct antiglobulin test (DAT). Column agglutination technology with micro-tubes containing gel and standard tube test methodology were used in IAT and DAT. Conclusion. Due to the limitations of the screening test in detecting antibodies to clinically significant low-frequency blood group antigens, such as Wr^a, the recommendation when selecting erythrocytes or transfusion is to use units that are cross-match compatible by the IAT test at 37 ºC. In the case of anti-Wr^a antibody, as well as in cases of other antibodies to low-frequency antigens, immunohematology findings should be confirmed in a national or international reference laboratory that has the structure, organization, as well as technical and professional capacities to provide this service.