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Blood compatibility testing is conducted in a medical laboratory to identify potential incompatibilities between blood types in blood transfusion. It is also used to diagnose and prevent some complications of pregnancy that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes blood typing, which detects the antigens on red blood cells that determine a person's blood type; testing for unexpected antibodies against blood group antigens ; and, in the case of blood transfusions, mixing the recipient's plasma with the donor's red blood cells to detect incompatibilities. Routine blood typing involves determining the ABO and RhD type, and involves both identification of ABO antigens on red blood cells and identification of ABO antibodies in the plasma. Other blood group antigens may be tested for in specific clinical situations.

Blood compatibility testing makes use of reactions between blood group antigens and antibodies—specifically the ability of antibodies to cause red blood cells to clump together when they bind to antigens on the cell surface, a phenomenon called agglutination. Techniques that rely on antigen-antibody reactions are termed serologic methods, and several such methods are available, ranging from manual testing using test tubes or slides to fully automated systems. Blood types can also be determined through genetic testing, which is used when conditions that interfere with serologic testing are present or when a high degree of accuracy in antigen identification is required.

Several conditions can cause false or inconclusive results in blood compatibility testing. When these issues affect ABO typing, they are called ABO discrepancies. ABO discrepancies must be investigated and resolved before the person's blood type is reported. Other sources of error include the "weak D" phenomenon, in which people who are positive for the RhD antigen show weak or negative reactions when tested for RhD, and the presence of immunoglobulin G antibodies on red blood cells, which can interfere with antibody screening, crossmatching, and typing for some blood group antigens.

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