Platelet reactive alloantibodies responsible for immune thrombocytopenia in Malay population
Background: Alloantibodies against human platelet alloantigens (HPAs) are responsible for the development of platelet transfusion refractoriness (PTR) in patients receiving random platelets and bleeding disorder in babies with fetal neonatal alloimmune thrombocytopenia (FNAIT). Recently, our results based on the analysis of the allelic distribution of HPAs indicated that immunization may occur among Malay. In this study, we sought to analyze the frequencies of platelet reactive alloantibodies responsible for FNAIT and PTR in Malaysia.
Methods: Sera from suspected FNAIT (n = 295) and PTR (n = 74) were collected in five years period (2008-2013) and tested for the presence of platelet reactive antibodies by the use of antigen capture assay.
Results: In 5/74 (5.41%) platelet specific antibodies against HPA-2b (n = 1), HPA-5a (n = 1), HPA-5b (n = 1), HPA-15b (n = 2) could be identified in our PTR cohort. In FNAIT cohort, platelet specific alloantibodies could be detected in 18 sera (6.10%) consisting anti-HPA-1a (n = 1), anti-HPA-3a (n = 3), anti-HPA-5a (n = 6), anti-HPA-5b (n = 6), anti-HPA-15a (n = 1), and anti-HPA-15b (n = 1).
Conclusion: Our study indicates that anti-HPA-3, -HPA-5 and -HPA-15 antibodies seems to be the most platelet specific antibodies involved in FNAIT and PTR cases in Malaysian population. Since similar HPA allelic distribution among Malaysian and Indonesian populations have been observed, immunization against these three HPA systems are expected to be the most potential risk of alloimmune mediated platelet disorders in Indonesia.
Metcalfe P, Watkins NA, Ouwehand WH, Kaplan C, Newman P, Kekomaki R, et al. Nomenclature of human platelet antigens. Vox Sang. 2003;85(3):240-5. http://dx.doi.org/10.1046/j.1423-0410.2003.00331.x
Juji T, Watanabe Y, Ishikawa Y, Fujiwara K, Tonami H, Tanaka H, et al. Human platelet alloantigen (HPA)-5a/b mismatch decreases disease-free survival in unrelated bone marrow transplantation. Tissue Antigens. 1999;54(3):229-34. http://dx.doi.org/10.1034/j.1399-0039.1999.540303.x
Mueller-Eckhardt C, Grubert A, Weisheit M, Mueller-Eckhardt G, Kiefel V, Kroll H, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 1989;333(8634):363-6. http://dx.doi.org/10.1016/S0140-6736(89)91733-9
Kiefel V, Konig C, Kroll H, Santoso S. Platelet antibodies in transfused patients. Transfusion. 2001;41(6):766-70. http://dx.doi.org/10.1046/j.1537-2995.2001.41060766.x
Kiefel V, Schönberner-Richter I, Schilf K. Anti-HPA-1a in a case of post-transfusion purpura: binding to antigen-negative platelets detected by adsorption/elution. Transfusion Med. 2005;15(3):243-7. http://dx.doi.org/10.1111/j.1365-3148.2005.00578.x
Veldhuisen B, Porcelijn L, Ellen van der Schoot C, de Haas M. Molecular typing of human platelet and neutrophil antigens (HPA and HNA). Transfus Apher Sci. 2014;50(2):189-99. http://dx.doi.org/10.1016/j.transci.2014.02.014
Tan J.Y, Lian L.H, Nadarajan V.S. Genetic polymorphisms of human platelet antigen-1 to -6 and -15 in the Malaysian population. Blood Transfusion. 2012;10(3):368-76.
Asmarinah, Dharma R, Ritchie N.K, Rahayu S, Putricahya E, Santoso S. Human platelet-specific antigen frequencies in Indonesian population. Transfus Med. 2013;23(4):250-3. http://dx.doi.org/10.1111/tme.12039
Kiefel V, Santoso S, Weisheit M, Müeller-Eckhardt C. Monoclonal antibody--specific immobilization of platelet antigens (MAIPA): a new tool for the identification of platelet-reactive antibodies. Blood. 1987;70(6):1722-6.
Campbell K, Rishi K, Howkins G, Gilby D, Mushens R, Ghevaert C, et al. A modified fast MAIPA for the detection of HPA antibodies: a multi-centre evaluation of a rapid monoclonal antibody specific immobilisation of platelet antigen (MAIPA) assay. Vox Sang. 2007;93: 289-97.
Saito S, Ota M, Komatsu Y, Ota S, Aoki S, Koike K, et al. Serologic analysis of three cases of neonatal alloimmune thrombocytopenia associated with HLA antibodies. Transfusion. 2003;43(7):908-17. http://dx.doi.org/10.1046/j.1537-2995.2003.00429.x
Tsuno NH, Matsuhashi M, Iino J, Nagura Y, Okazaki H, Santoso S. The importance of platelet antigens and antibodies in immune-mediated thrombocytopenia. ISBT Science Series. 2014;9(1):104-11. http://dx.doi.org/10.1111/voxs.12086
Sidiropoulos D, Straume B. The treatment of neonatal isoimmune thrombocytopenia with intravenous immunoglobulin. Blut. 1984;48:383-56. http://dx.doi.org/10.1007/BF00319967
Roberts I, Stanworth S, Murray NA. Thrombocytopenia in the neonates. Blood reviews. 2008;22(4):173-86. http://dx.doi.org/10.1016/j.blre.2008.03.004
Warkentin TE, Smith JW, Hayward CP, Ali AM, Kelton JG. Thrombocytopenia caused by passive transfusion of anti-glycoprotein Ia/IIa alloantibody (anti-HPA-5b). Blood. 1992;79(9):2480-4.
Ertel K, Al-Tawil M, Santoso S, Kroll H. Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenia syndromes. Transfusion. 2005;45(3):366-73. http://dx.doi.org/10.1111/j.1537-2995.2005.04281.x
Socher I, Kroll H, Jorks S, Santoso S, Sachs UJH. Heparin-independent activation of platelets by heparin-induced thrombocytopenia antibodies: a common occurance. J Thromb and Haemost. 2008;6(1):197-200. http://dx.doi.org/10.1111/j.1538-7836.2007.02815.x
Matsuhashi M, Tsuno NH, Sone S, Mishima Y, Nagura Y, Watanabe-Okochi N, et al. The role of alloantibodies against human platelet antigen-15 in multiply platelet transfused patients. Transfusion. 2014;54(4):1093-9. http://dx.doi.org/10.1111/trf.12455
Copyright (c) 2014 Mohd I. Armawai, Afifah Hassan, Hevi Wihadmadyatami, Sentot Santoso
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.