Red Cell Reference

Investigating antigen/antibody problems

The Red Cell Reference department deals exclusively in complex and difficult red cell antigen/antibody problems.

These problems take the form of:

  • Antibody identification when the referring laboratory has been unable to elucidate a serological incompatibility. These are usually from patients whose sera react with all red cells and for whom a compatible donor is difficult or impossible to find. The reactions may be due to a complex mixture of antibodies or to the presence of an antibody to a high incidence antigen produced by a patient with a rare red cell phenotype. Sometimes both occur in the same patient.
  • Antibody confirmation when the referring laboratory needs verification of an antibody specificity which is suspected but not proven. Cells with rare types are needed to exclude the presence of underlying antibodies to ‘routine’ blood groups.
  • Elucidation of rare or novel blood group antigens on the red cells of patients or donors. When confirmed, donors may be registered for the National or International Rare Donor Panels or provide rare cells for exchange schemes.
  • Identification of low incidence antigens responsible for haemolytic disease of the newborn or crossmatch incompatibility.

Clinical Usefulness

Antibody identification may suggest potential clinical significance or act as a guide to the likely availability of compatible donors at a local level or via the National or International Rare Donor Panels.


Techniques used as an adjunct to serology in difficult cases include MAIEA, flow cytometry, molecular biology and immunoblotting.

Referring Investigations

Red cell serology services are only provided to UK Blood Centres and to bona-fide reference centres outside the UK. 

Centres wishing to refer for the first time must contact IBGRL to discuss the appropriateness of the proposed investigation.

Other types of referrals can be considered but please telephone to discuss the case before sending samples.

Type of Investigation Description Samples required Notes
Investigation of antibody to a high-incidence antigen or a mixture of antibodies Patient (or donor) whose serum/plasma contains antibody(ies) to all or the majority of red cells (i.e. antibody to a high incidence antigen or a complex mixture of antibodies) 10ml clotted blood PLUS 10ml anticoagulated blood Includes confirmation of rarity previously determined by the referrer and determination of possible underlying specificities. Larger samples are preferable and sometimes may be essential. Anticoagulated samples should not be separated. Separation of clotted samples is optional.
Investigation of antibody to a low-incidence antigen Patient (or donor) whose serum/plasma contains antibody to a single example of donor cells or the baby’s/fathers cells in case of maternal antibody (i.e. antibody to a low incidence antigen). Minimum of 10ml clotted blood from the patient PLUS 10ml anticoagulated blood from the incompatible donor/father (less from a baby). This type of investigation cannot be carried out unless the incompatible cells are received. The incompatibility should have a minimum 3+ reaction ( on a scale of 1+ to 5+).
Difficult or discrepant typing (any phenotype) Minimum of 10ml anticoagulated sample. ABO problems and partial D problems with anti-D cannot be investigated without either plasma or serum for antibody confirmation

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