High Prevalence of Antiphospholipid Antibodies in Children with Non-Transfusion Dependent Thalassemia and Possible Correlations with Microparticles Antiphospholipid Antibodies and Thalassemia in children

Main Article Content

Jitlada Chinsuwan
Phatchanat Klaihmon
Praguywan Kadegasem
Ampaiwan Chuansumrit
Anucha Soisamrong
Kovit Pattanapanyasat
Pakawan Wongwerawattanakoon
Nongnuch Sirachainan

Keywords

Thalassemia disease; Antiphospholipid antibody; Microparticles

Abstract

Antiphospholipid antibodies (APAs) are developed antibodies to the phospholipid surfaces or to the proteins binding to phospholipids. Increased PS-expressed red blood cells (RBC) may be a risk factor in APAs development. There were only a few studies reported on APAs in thalassemia, and their associations to PS-expressing microparticles (MPs), remain unknown. The presence of antiphospholipid antibodies (APAs) in pediatric thalassemia patients and their associations with phosphatidylserine (PS)- expressing microparticles (MPs), a previously unexplored relationship, were the aims of this report. We identified that positive APA rates were highest in non-transfusion-dependent thalassemia (NTDT) subjects, followed by transfusion-dependent thalassemia (TDT) subjects and controls (29.5%, 18.2% and 17.9%, respectively).  Subgroup analysis demonstrated that positive anti- ?2 glycoprotein I (a?2-GPI)- IgG rates in NTDT subjects were significantly greater than in controls and that the percentage of MPs was also significantly elevated in thalassemia subjects. More specifically, there were significant correlations found between a?2GPI-IgG and anticardiolipin (aCL)-IgM APAs, and MPs.

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References

1. Greenberg PL, Gordeuk V, Issaragrisil S, Siritanaratkul N, Fucharoen S, Ribeiro RC. Major hematologic diseases in the developing world- new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia. Hematology Am Soc Hematol Educ
Program. 2001;1:479-498. https://doi.org/10.1182/asheducation-2001.1.479 PMid: 11723000
2. Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353(11):1135-1146. https://doi.org/10.1056/NEJMra050436 PMid: 16162884
3. Bonifazi F, Conte R, Baiardi P, Bonifazi D, Felisi M, Giordano P, et al. Pattern of complications and burden of disease in patients affected by beta thalassemia major. Curr Med Res Opin. 2017;33(8):1525-1533. https://doi:10.1080/03007995.2017.1326890 PMid: 28471307
4. Logothetis J CM, Economidou J, Stefanis C, Hakas P, Augoustaki O, Sofroniadou K, et al. Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology. 1972;22(3):294-304.
https://doi:10.1212/wnl.22.3.294 PMid: 5062264
5. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000;111(2):467-473. https://doi:10.1046/j.1365-2141.2000.02376.x.
PMid: 11122086
6. Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood. 2002;99(1):36-43. https://doi:10.1182/blood.v99.1.36 PMid: 11756150
7. Kheansaard W, Phongpao K, Paiboonsukwong K, Pattanapanyasat K, Chaichompoo P, Svasti S. Microparticles from ?-thalassaemia/HbE patients induce endothelial cell dysfunction. Sci Rep. 2018;8(1):13033. https://doi:10.1038/s41598-018-31386-6
PMid: 30158562 PMCid: PMC6115342
8. Klaihmon P, Vimonpatranon S, Noulsri E, Lertthammakiat S, Anurathapan U, Sirachainan N et al. Normalized levels of red blood cells expressing phosphatidylserine, their microparticles, and activated platelets in young patients with ?-thalassemia following bone marrow
transplantation. Ann Hematol. 2017;96(10):1741-1747. https://doi:10.1007/s00277-017-3070-2 PMid: 28748286
9. Youssry I, Soliman N, Ghamrawy M, Samy RM, Nasr A, Abdel Mohsen M. Circulating microparticles and the risk of thromboembolic events in Egyptian beta thalassemia patients. Ann Hematol. 2017;96:597-603. https://doi:10.1007/s00277-017-2925-x PMid: 28168351
10. Rai R, Swetha T. Association of anti-phospholipid antibodies with connective tissue diseases. Indian Dermatol Online J. 2015;6(2):89-91. https://doi:10.4103/2229-5178.153009 PMid: 25821728
11. Islam MA, Alam SS, Kundu S, Prodhan AHMSU, Khandker SS, Reshetnyak T, et al. Prevalence of antiphospholipid antibodies in Behçet's disease: A systematic review and meta-analysis. PLoS One. 2020;15(1):e0227836. https://doi:10.1371/journal.pone.0227836 PMid: 31929597
PMCid: PMC6957187
12. Liu A, Zhang H. Detection of antiphospholipid antibody in children with Henoch-Schönlein purpura and central nervous system involvement. Pediatr Neurol. 2012;47(3):167-170. https://doi:10.1016/j.pediatrneurol.2012.05.024 PMid: 22883280
13. Urbanus RT, Derksen RH, de Groot PG. Current insight into diagnostics and pathophysiology of the antiphospholipid syndrome. Blood Rev. 2008;22(2):93-105. https://doi:10.1016/j.blre.2007.09.001 PMid: 17964017
14. Kashef S, Karimi M, Amirghofran Z, Ayatollahi M, Pasalar M, Ghaedian MM, et al. Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patients. Int J Lab Hematol. 2008;30(1):11-16. https://doi:10.1111/j.1751-553X.2007.00916.x. PMid: 18190462
15. Sharma S, Raina V, Chandra J, Narayan S. Lupus anticoagulant and anticardiolipin antibodies in polytransfused betathalassemia major. Hematology. 2006;11(4):287-290. https://doi:10.1080/10245330600954130. PMid: 17178669
16. Versteeg HH, Ruf W. Thiol pathways in the regulation of tissue factor pro-thrombotic activity. Curr Opin Hematol. 2019;119(6):860-870. https://doi:10.1055/s-0039-1681102. PMid: 30861549
17. de Laat B, Wu XX, van Lummel M, Derksen RH, de Groot PG, Rand JH. Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5. Blood. 2007;109(4):1490-1494.
https://doi:10.1182/blood-2006-07-030148. PMid: 17053060
18. Urbanus RT, Pennings MT, Derksen RH, de Groot PG. Platelet activation by dimeric beta2-glycoprotein I requires signaling via both glycoprotein Ibalpha and apolipoprotein E receptor 2'. J Thromb Haemost. 2008;6(8):1405-1412. https://doi:10.1111/j.1538-7836.2008.03021.x.
PMid: 18485085
19. Shi T, Giannakopoulos B, Yan X, Yu P, Berndt MC, Andrews RK, et al. Anti-beta2-glycoprotein I antibodies in complex with beta2-glycoprotein I can activate platelets in a dysregulated manner via glycoprotein Ib-IX-V. Arthritis Rheum. 2006;54(8):2558-2567.
https://doi:10.1002/art.21968. PMid: 16868978
20. Gardiner C, Hills J, Machin S, Cohen H. Diagnosis of antiphospholipid syndrome in routine clinical practice. Lupus. 2013;22(1):18-25. https://doi:10.1177/0961203312460722. PMid: 22988029 PMCid: PMC4108293
21. Giordano P, Tesse R, Lassandro G, Fracchiolla D, Ranieri P, Lotito A, et al. Clinical and laboratory characteristics of children positive for antiphospholipid antibodies. Blood Transfus. 2012;10(3):296-301. https://doi:10.2450/2011.0069-11. PMid: 22244004 PMCid: PMC3417728
22. Biggioggero M, Meroni PL. The geoepidemiology of the antiphospholipid antibody syndrome. Autoimmun Rev. 2010;9(5):A299-304. https://doi:10.1016/j.autrev.2009.11.013. PMid: 19932199
23. Giordano P, Galli M, Del Vecchio GC, Altomare M, Norbis F, Ruggeri L. Lupus anticoagulant, anticardiolipin antibodies and hepatitis C virus infection in thalassaemia. Br J Haematol. 1998;102(4):903-906. https://doi:10.1046/j.1365-2141.1998.00853.x. PMid: 9734637
24. Atichartakarn V, Chuncharunee S, Chandanamattha P, Likittanasombat K, Aryrachai K. Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/?-thalassemia patient. Blood.
2004;103(7):2844-2846. https://doi:10.1182/blood-2003-09-3094 PMid: 14645000
25. Pittoni V, Isenberg D. Apoptosis and antiphospholipid antibodies. Semin Arthritis Rheum. 1998;28(3):163-178. https://doi:10.1016/s0049-0172(98)80033-4 PMid: 9872477
26. Del Vecchio GC, Schettini F, Piacente L, De Santis A, Giordano P, De Mattia D. Effects of deferiprone on immune status and cytokine pattern in thalassaemia major. Acta Haematol. 2002;108(3):144-149. https://doi:10.1159/000064705. PMid: 12373086
27. Khamashta M, Taraborelli M, Sciascia S, Tincani A. Antiphospholipid syndrome. Best Pract Res Clin Rheumatol. 2017;151 Suppl 1:S43-S47. https://doi:10.1016/S0049-3848(17)30066-X. PMid: 28262233