Immunological Platelet Refractoriness

Platelet refractoriness is defined as a platelet Corrected Count Increment (CCI) of less than 4000 per μL per m2 per 1011 platelets 1 hour post transfusion.

 

This measure of platelet refractoriness however requires knowledge of the patient’s height and weight at the time of transfusion in order to calculate the Body Surface Area. This is not always possible to obtain. For practical purposes therefore, platelet refractoriness often is defined as a failure to obtain a platelet count increment (PCI) of more than 10 x 109/l between 1 and 24 hours post transfusion with ABO compatible platelets on at least two separate occasions. This measure does not take body surface area into account.

 

Platelet refractoriness has immune as well as non immune causes. Non immune causes account for 80% of platelet refractoriness and include active bleeding, infection, splenomegally, dissemination intravascular coagulation (DIC) and some medication such as Amphotericin B. The main immune cause of platelet refractoriness is the presence of anti-HLA antibodies (95% of immune refractoriness) though immune refractoriness can also be caused by anti-HPA antibodies and high titre anti ABO antibodies.

 

HLA antibodies cause platelet refractoriness by binding to the donor platelets which are then removed in the spleen by resident macrophages. The patients’ platelet count therefore fails to rise, making the patient refractory to random platelets. Such patients are supported with HLA ‘matched’ platelets. Laboratory investigations undertaken to support the provision of HLA matched platelets include patient HLA typing at the HLA-A and B loci (matching is at HLA-A and B only) and Class I HLA antibody screening and identifications. Donors need to be HLA class I typed. HLA typing is currently mainly undertaken by low to medium resolution DNA based techniques as matching is undertaken to the split serological level. HLA antibody screening and identification has historically been by cell based techniques such as the complement dependent cytotoxicity (CDC) assay or by cell based flowcytometric assays. Currently however, most HLA antibody testing in the UK is by the solid phase Luminex bead based assays. These assays are much more sensitive than the traditional CDC techniques. Accurate HLA antibody definition permits the identification of ‘windows’ or HLA specificities that the patient does not have antibodies against and which will therefore be permitted mismatches for that patient during donor selection.

 

Where patients do not respond to HLA matched platelets, anti-HPA antibodies investigation may be undertaken. Antibodies against all of the HPA antigens have been implicated in platelet refractoriness, including HPA-1, 2, 3, 4, 5 and 15. Techniques most commonly used include the flowcytometric Platelet immunofluorescence Test (PIFT) and the Monoclonal Antibody specific Immobilisation of Platelet Antigens (MAIPA) test which uses platelet antigen specific monoclonal antibodies to specifically capture platelet antigens and is therefore useful for differentiating HPA from HLA antibodies. Provision of HPA matched platelets requires that donor be typing HPA typed for the common platelet antigens.

 

Where ABO incompatible donors are being used, donors with high titre anti ABO antibodies need to be avoided.

 

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