The transfusion of ABO‐incompatible red cells can lead to intravascular haemolysis, where the recipient's anti‐A and/or anti‐B IgM antibodies bind to the corresponding surface antigens of the transfused cells (Norfolk [202]). Complement activation results in lysis of the transfused cells and the haemoglobin that is released precipitates renal failure, with the fragments of the lysed cells activating the clotting pathways, which in turn leads to the development of disseminated intravascular coagulation (Klein and Anstee [127]).

Transfusion of Rh D‐positive cells to a Rh D‐negative individual will result in immunization and the appearance of anti‐D antibodies in at least 30% of recipients (Daniels [54]). If the person is immunized and undergoes any subsequent exposure to D‐positive red cells, extravascular haemolysis occurs as Rh antibody‐coated red cells are destroyed by macrophages in the liver and spleen (McClelland [151]). This can present as a severe immediate or delayed haemolytic transfusion reaction (Daniels [54]).

A patient's Rh status is of particular importance if they are female and of child‐bearing age or require a transfusion during pregnancy. Immunization can happen by two processes: transfusion of D‐positive cells into someone who is D negative, or in pregnancy when transplacental passage of foetal red cells exposes the mother to D‐positive cells. When the mother is Rh D negative and the developing foetus is Rh D positive, the exposure to foetal blood can stimulate anti‐D activation in the mother. Anti‐D is one of the red cell antibodies that can cross the placenta and cause haemolysis of the foetal blood, which results in what is known as ‘haemolytic disease of the foetus and newborn’ (HDFN) (Norfolk [202]).

The human leucocyte antigen (HLA) is used to determine compatibility for organ transplantation, including bone marrow and peripheral blood stem cells. However, because the ABO blood groups and HLA tissue types are determined genetically, it is common to find a suitable HLA donor who is ABO and/or Rh incompatible with the recipient. Approximately 20–40% of allogeneic haemopoietic stem cell transplantation (HSCT) recipients receive grafts from ABO‐mismatched donors (Tekgündüz and Özbek [268]). In such circumstances, major transfusion reactions can be avoided by red cell and/or plasma depletion of the donor cells in the laboratory before reinfusion (Mollison et al. [162]). However, collection of peripheral stem cells by apheresis usually results in a product that has a low red cell haematocrit and therefore further removal of mature red cells is not necessary before the product is cryopreserved (Mian et al. [160]).