The importance of platelet antigens and antibodies in immune mediated thrombocytopenia
ISBT Education. Tsuno N. 12/01/13; 48043; 1D-H8-01 Topic: Platelet antibodies
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Dr. Nelson H. Tsuno
Dr. Nelson H. Tsuno
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After viewing this presentation, the participant will be able to understand the clinical conditions in which anti-platelet alloantibodies are involved, the mechanism of the disease, the clinical picture, and the methods for their prevention and/or treatment. Also, the participant will understand the difference in the frequency distribution of human platelet antigens (HPA) between Caucasian and Asian, and the importance of the development of the platelet immunology field in Asia.
Antibodies directed to human platelet antigens (HPA) play important roles in the pathogenesis of neonatal alloimmune thrombocytopenia (NAIT), platelet transfusion refractoriness (PTR) and post-transfusion purpura (PTP). Presently, 6 HPA biallelic systems, namely HPA-1 to -5 and -15, which are involved in immune mediated thrombocytopenia, are characterized. There are important ethnic differences in the frequency distribution of these HPA systems, the incompatibility of the HPA-1 system being the mostly involved in thrombocytopenic conditions in Caucasian, whereas in Japanese, the HPA-4 system is the mostly involved. The frequency distribution of HPA systems reported in other parts of Asia seems to be different from Caucasian as well as Japanese, especially related to HPA-1 and -4, respectively.
In addition to HPA, antibodies to human leukocyte antigen (HLA), blood group ABO, and human neutrophil antigens (HNA) have also been shown to be involved in immune mediated thrombocytopenia. In fact, the majority of the cases of PTR are dependent on anti-HLA antibodies, and anti-HPA antibodies comprise only a small proportion. The identification of the causative antibody is very important for the implementation of preventive/therapeutic measures for PTR, such as the selection of HLA- and/or HPA-compatible platelets. On the other hand, the involvement of anti-HLA antibodies in the pathogenesis of NAIT is questioned, but cases in which the causative antibody cannot be determined still remain relatively high.
Thus, for the implementation of preventive and therapeutic measures for the immune mediated thrombocytopenia, the detection and identification of the causative antibody is essential. The standard methods applied varies among the regions, the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and the platelet immunofluorescence test (PFIT) being the preferred methods in the US and Europe, whereas in Japan, the mixed-passive hemagglutination is the most applied one. Neither of the methods alone, however, is able to detect all the clinically significant antibodies, thus, improvement of the available methods as well as the development of new technologies is required.
Considering the ethnical differences of the HPA frequency distribution, we considered important to develop the research of this field also in Asia, and for this purpose, the ISBT Platelet Immunobiology Working Party, Asia Regional (ISBT PIWP-AR) was launched in 2010, during the XXXIst International Congress of the ISBT in Berlin, which aims the sharing of knowledge and improvement of technology in Asia. A training course on platelet immunology methods and genotyping was provided in Tokyo in 2010, and the first workshop of the PIWP-AR was organized in Taipei in 2011. In May 2013, the second training course on platelet immunology methods and genotyping was organized in Guangzhou, China, and the 2nd workshop of the PIWP-AR is going to be held in Kuala Lumpur, Malaysia, during the 24th Regional Congress of the ISBT.
The presently available methods for the antigen/antibody testing, the problems related with antibody detection, and the activities of the Platelet Working Party will be presented.
Antibodies directed to human platelet antigens (HPA) play important roles in the pathogenesis of neonatal alloimmune thrombocytopenia (NAIT), platelet transfusion refractoriness (PTR) and post-transfusion purpura (PTP). Presently, 6 HPA biallelic systems, namely HPA-1 to -5 and -15, which are involved in immune mediated thrombocytopenia, are characterized. There are important ethnic differences in the frequency distribution of these HPA systems, the incompatibility of the HPA-1 system being the mostly involved in thrombocytopenic conditions in Caucasian, whereas in Japanese, the HPA-4 system is the mostly involved. The frequency distribution of HPA systems reported in other parts of Asia seems to be different from Caucasian as well as Japanese, especially related to HPA-1 and -4, respectively.
In addition to HPA, antibodies to human leukocyte antigen (HLA), blood group ABO, and human neutrophil antigens (HNA) have also been shown to be involved in immune mediated thrombocytopenia. In fact, the majority of the cases of PTR are dependent on anti-HLA antibodies, and anti-HPA antibodies comprise only a small proportion. The identification of the causative antibody is very important for the implementation of preventive/therapeutic measures for PTR, such as the selection of HLA- and/or HPA-compatible platelets. On the other hand, the involvement of anti-HLA antibodies in the pathogenesis of NAIT is questioned, but cases in which the causative antibody cannot be determined still remain relatively high.
Thus, for the implementation of preventive and therapeutic measures for the immune mediated thrombocytopenia, the detection and identification of the causative antibody is essential. The standard methods applied varies among the regions, the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and the platelet immunofluorescence test (PFIT) being the preferred methods in the US and Europe, whereas in Japan, the mixed-passive hemagglutination is the most applied one. Neither of the methods alone, however, is able to detect all the clinically significant antibodies, thus, improvement of the available methods as well as the development of new technologies is required.
Considering the ethnical differences of the HPA frequency distribution, we considered important to develop the research of this field also in Asia, and for this purpose, the ISBT Platelet Immunobiology Working Party, Asia Regional (ISBT PIWP-AR) was launched in 2010, during the XXXIst International Congress of the ISBT in Berlin, which aims the sharing of knowledge and improvement of technology in Asia. A training course on platelet immunology methods and genotyping was provided in Tokyo in 2010, and the first workshop of the PIWP-AR was organized in Taipei in 2011. In May 2013, the second training course on platelet immunology methods and genotyping was organized in Guangzhou, China, and the 2nd workshop of the PIWP-AR is going to be held in Kuala Lumpur, Malaysia, during the 24th Regional Congress of the ISBT.
The presently available methods for the antigen/antibody testing, the problems related with antibody detection, and the activities of the Platelet Working Party will be presented.
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