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Why can an ABO-incompatible blood transfusion cause a dangerous reaction?

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Close-up illustration of multiple human red blood cells with their characteristic disc shape, floating against a red background. — blood group The major component of human blood is the red blood cell.

An ABO-incompatible blood transfusion is dangerous because it triggers a rapid, potentially fatal immune response known as an intravascular hemolytic reaction.12

The human ABO blood group system is defined by the presence or absence of A and B antigens on the surface of red blood cells. Individuals naturally possess antibodies in their serum that oppose antigens they lack; for example, a person with type A blood has anti-B antibodies.32

When incompatible blood is transfused, these pre-existing antibodies recognize the donor's red blood cells as foreign "nonself" substances. The antibodies bind to the donor cells and initiate an immune attack that destroys the transfused red blood cells within the recipient's blood vessels. This process can lead to severe complications and, in some cases, death. To prevent these reactions, medical professionals must perform compatibility testing, such as the direct match test, to ensure the donor's cells are safe for the specific recipient.4132