ALLOIMMUNIZATION TO PLATELET TRANSFUSIONS
Authors: von dem Borne A E G Kr , Ouwehand W H 
Published: August 2018

Alloimmunization against platelets is an important cause of refractioness to transfusion of this blood product.It may occur in up to 66% of patients, with malignant blood diseases or aplastic anaemia, whoreceive platelet transfusions for thrombocytopenia.The alloantibodies responsible for refractioness areoften anti-HLA-ABC antibodies, but in about 20% platelet specific allo- antibodies may (also) play a role.

In recent years major progress has been made in the methodology of platelet antibody detection. Reliabletechniques to detect platelet antibodies and antigens have been developed, based on the antiglobulin principle. Platelet immunofluorescence is the standard and reference method, but platelet radio-immuno assays and enzyme-linked immuno-assay appear to be good alternatives. A problem is still the quality of the antiglobulin reagents applied, which appears to be often poor.

A new development is the study of antibody binding at the level of platelet membrane glycoproteins, instead of intact platelets. This can be done in the immunoblot, but also with chemically purified glycoproteins, or glycoproteins specifically captured by monoclonal antibodies. It gives direct information aboutthe chemical structures involved in the alloimmune response. Most of these methods are still in the investigational stage, but the immunoblot has already found a place in the routine laboratory. A limitation of the immunoblot is that it is quite insensitive and often gives non-specific results.

An important question in platelet serology is whether a positive platelet antibody test is due to HLA-antibodies or to platelet specific antibodies. To answer this question, combined tests on platelets and lymphocytes, obtained from the same donor, are usuallyperformed. Complicated studies on cell panels of typed donors, with absorptions and elutions, may often be necessary.However chloroquine treatment of the platelets, which leads to elution of HLA-antigens, isthan a very helpfull new technique, as are techniqueswhich use isolated glycoproteins.

Platelet specific antibodies may be directed againsthidden or cryptic antigens of glycoprotein Ilb/IIIa, which are exposed upon alteration of the platelets, for instance by fixation or Na2EDTA.The recognition of such antibodies is important, because they are not responsible for increased platelet destruction and may cause 'falsely 'positive test results.

Modern platelet antibody technology has made it possible to perform platelet crossmatching. In refractory patients an obvious first approach is the selection of platelets from cross-match negative random donors. In many patients satisfactory platelets increments can be obtained again in this way. Only in patients with multiple HLA antibodies in the blood, HLA-typing and the transfusion of HLA-compatible donor platelets is than necessary.

HLA-alloimmunization occurs much more frequently on blood products that contain leukocytes. It has been postulated that mixed lymphocyte reactions, which take place between the lymphocytes of the donor and the patient in vivo, are an important stimulus for theimmunization to occur. Leukocyte depletion of blood products (red cells, platelets) is therefore advicedto prevent it. This can be done by differential centrifugation, but also by cotton wool filtration. However the best method is not yet know and controlled studies are badly needed.