Platelet Donor Database: A Study on the Specialist Donor Database for the Patients with Alloimmune Thrombocytopenia in the Chinese Population and the Assessment of Completeness
Alloimmune thrombocytopenia is a critical condition that arises due to the immune response against platelet antigens, leading to various clinical manifestations such as immune platelet transfusion refractoriness, post-transfusion purpura, and fetal/neonatal alloimmune thrombocytopenia. The immunogenicity of platelet antigens, including blood group antigens (e.g., ABO antigens), human leukocyte antigen (HLA), human platelet antigen (HPA), and CD36 (platelet glycoprotein IV), plays a significant role in the development of these conditions. These antigens can induce the production of alloantibodies through immune factors such as blood transfusion, pregnancy, and drug exposure. Platelet transfusion is a vital therapeutic approach for managing alloimmune thrombocytopenia. However, the effectiveness of platelet transfusion depends on the availability of antigen-negative platelets, which do not react with the alloantibodies present in the patient’s body. To ensure the availability of such platelets, establishing a comprehensive platelet donor database (PDD) with a sufficient number of donors characterized for their platelet antigens or genotypes is essential. This study focuses on the design and establishment of a PDD tailored for the Chinese population, particularly in the Nanning area, and evaluates its completeness in meeting the needs of patients with alloimmune thrombocytopenia.
The immunogenicity of platelet antigens varies across different populations due to the racial characteristics of antigen polymorphisms and related genes. In the Chinese population, anti-CD36 antibodies are a significant cause of alloimmune thrombocytopenia, alongside the more commonly recognized anti-HLA and anti-HPA antibodies. The incidence of anti-CD36-mediated alloimmune thrombocytopenia is second only to that mediated by anti-HLA antibodies, which is attributed to the high prevalence of CD36 deficiency in the Chinese population (1.80%–4.13%). In contrast, anti-CD36 antibodies are rare in the Caucasian population, where the prevalence of CD36 deficiency is less than 0.40%. This highlights the importance of considering population-specific antigen characteristics when designing a PDD.
The study was conducted in the Nanning area of China, a multi-ethnic region with a population of over 7 million people. Nanning has the highest reported incidence of CD36 deficiency in China, making it an ideal location for this research. The study analyzed the characteristics of platelet antigens and related antibodies in the local population based on data collected from 265 cases of tested and identified platelet antibody specificity between 2007 and 2019. Among these cases, anti-HLA antibodies were the most prevalent (89.17%, 231/265), followed by anti-CD36 antibodies (8.30%, 22/265), and a small number of cases involving anti-HPA antibodies or combinations of these antibodies. These findings underscore the importance of considering HLA, HPA, and CD36 antigens in the design of a PDD for the Chinese population.
To construct the PDD, the study analyzed the polymorphisms of HLA-A and -B genes, the cross-reactive groups (CREGs) of the population, and the HPA-1-17w gene polymorphisms in the Nanning area. The data were derived from 7,001 samples for HLA-A and -B, 4,243 samples for HPA-1-17w, and 5,081 samples for CD36 deficiency and ABO blood group distribution among apheresis platelet donors. Based on these analyses, a PDD was established, consisting of donors with known HLA, HPA, and CD36 deficiency status. The completeness of the PDD was evaluated using a criterion that ensures at least one matched donor for a random recipient. The probability of achieving this criterion was calculated using a formula developed by Müller et al., which considers the frequency of specific antigen phenotypes or genotypes and the number of donors in the database.
The study found that the completeness of the PDD increased with the number of donors characterized for their HLA-A and -B genotypes, HPA-1-17w genotypes, and CD36 deficiency status. For a 99% completeness of the PDD, the study estimated that 9,516 donors with known HLA-A and -B genotypes, 1,728 donors with known HPA-1-17w genotypes, and 33 donors with CD36 deficiency would be required. The currently established PDD in Nanning (Nanning Platelet Donor Database, NNPDD) includes 1,813 donors with known HLA and HPA genotypes and 209 donors with CD36 deficiency. The completeness of the NNPDD was calculated to be 90.23% for HLA-A and -B CREGs, 99.04% for HPA-1-17w, and 100.00% for CD36 deficiency, ensuring that a random local recipient would have at least one donor with fully matched antigens.
The NNPDD has already been utilized in clinical transfusion therapy in the Nanning area. For patients with alloimmune thrombocytopenia requiring platelet transfusion, matched platelets were selected from the NNPDD based on a strategy that ensures the platelets do not react with the patient’s antibodies and are negative for relevant antigens. The study emphasizes the need for continuous improvement of the PDD by increasing the number of donors with known HLA and HPA genotypes and maintaining financial support for the database. The model and completeness assessment developed in this study are not only applicable to the Chinese population but can also be adapted for other populations worldwide.
In conclusion, this study provides a comprehensive approach to designing and establishing a platelet donor database tailored for patients with alloimmune thrombocytopenia in the Chinese population. By analyzing the characteristics of platelet antigens and related antibodies in the Nanning area, the study highlights the importance of considering population-specific antigen profiles in the development of a PDD. The NNPDD demonstrates high completeness in providing matched donors for patients, thereby improving the outcomes of platelet transfusion therapy. The findings of this study have broader implications for the development of similar databases in other regions, contributing to the advancement of transfusion medicine globally.
doi.org/10.1097/CM9.0000000000001561
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