Platelet-Derived Microparticle Count in β-Thalassemia Patients with Direct Labeling Monoclonal Antibody CD62P and CD41

Ivan Lumban Toruan, Pandji Irani Fianza, Delita Prihatni

Abstract


Thromboembolic events are potentially life-threatening clinical complications found in β-thalassemia patients. The pathogenesis of the hypercoagulable state in β-thalassemia patients results from the degradation of excess α-globin chains in red blood cells, leading to intracellular labile iron accumulation, oxidative stress, and more rigid, deformed, and eventually prematurely damaged red blood cells. This process is associated with the loss of the normal asymmetrical distribution of membrane phosphatidylserine and its exposure to the outer surface of the blood cell membrane resulting in the formation of tenase complexes, prothrombinase, and thrombin complexes. Increased thrombins lead to platelet activation and platelet-derived microparticles synthesis, which in turn contributes to thrombus formation. This study aimed to determine the increase in the platelet-derived microparticle count by direct labeling of CD62P and CD41 monoclonal antibodies in β-thalassemia patients when compared with normal subjects. This was a cross-sectional analytical quantitative study conducted in Dr. Hasan Sadikin General Hospital Bandung and Dharmais Cancer Hospital Jakarta Indonesia between August and September 2019. Sixty patients, divided evenly into β-thalassemia group and control group, were labeled by CD62P and CD41 monoclonal antibodies. Results showed that the β-thalassemia group had a platelet count of 197x103/uL (58–1,261) with a median count for platelet-derived microparticles of 10,553 events/uL (779–90,971) as opposed to 1,861 events/uL (1,244–3,174) in the normal group (p<0.05). Therefore, the platelet-derived microparticle count in the β-thalassemia patients is 5.7 times greater than in the normal subjects.



Jumlah Platelet Derived Microparticles pada Pasien Thalassemia β dengan Metode Pelabelan Langsung Antibodi Monoklonal CD62P dan CD41


Kejadian tromboemboli berpotensi komplikasi klinis yang mengancam jiwa ditemukan pada pasien thalassemia β. Patogenesis keadaan hiperkoagulasi pada pasien thalassemia β akibat dari degradasi rantai globin α berlebih dalam sel darah merah yang menghasilkan akumulasi besi labil intraseluler, dan mengarah pada stres oksidatif serta sel darah merah yang lebih kaku dan cacat, dengan akibat kerusakan prematur. Proses ini dikaitkan dengan hilangnya distribusi asimetris normal dari fosfatidilserin membran dan paparannya pada permukaan luar membran sel darah, yang meyebabkan pembentukan kompleks tenase, kompleks protrombinase dan trombin. Peningkatan trombin mengarah pada aktivasi trombosit dan sintesis platelet derived microparticles yang selanjutnya berkontribusi pada pembentukan trombus. Tujuan dari penelitian ini adalah mengetahui peningkatan jumlah platelet derived microparticles dengan metode pelabelan langsung antibodi monoklonal CD62P dan CD41 pada pasien thalassemia β dibanding dengan subjek normal. Penelitian ini merupakan suatu penelitian kuantitatif dengan metode analitik potong lintang yang dilakukan di RSUP Dr. Hasan Sadikin Bandung dan Rumah Sakit Kanker Dharmais Jakarta antara bulan Agustus dan September 2019. Enam puluh pasien, dibagi secara merata menjadi kelompok thalassemia β dan kelompok kontrol, diberi label oleh CD62P dan CD41 antibodi monoklonal. Hasil penelitian menunjukkan kelompok thalassemia β memiliki jumlah trombosit 197x103/uL (58–1.261) dengan jumlah median platelet derived microparticles 10.553 partikel/uL (779–90.971) dibanding dengan 1.861 partikel/uL ( 1,244–3,174) pada kelompok normal (p<0,05). Simpulan, jumlah platelet derived microparticles  pada pasien thalassemia β adalah 5,7 kali lebih besar daripada pada subjek normal.

Keywords


hypercoagulation, monoclonal antibodies, phosphatidylserine, platelet derived microparticles, thalassemia.

Full Text:

PDF

References


Pattanapanyasat K, Gonwong S, Chaichompoo P, Noulsri E, Lerdwana S, Sukapirom K, et al. Activated platelet-derived microparticles in thalassemia. Br J Haematol. 2007;136(3): 462–71.

Cappellini MD, Musallam KM, Marcon A, Taher AT. Coagulopathy in beta-thalassemia: current understanding and future perspective. Mediterr J Hematol Infect Dis. 2009;1(1):e2009029.

Mishra G, Saxena R, Mishra A, Tiwari A. Recent techniques for the detection of β-thalassemia: a review. J Biosens Bioelectron. 2012;3(4):1–5.

Trinchero A, Marchentti M, Giaccherini C, Tartari CJ, Russo L, Falanga A. Platelet haemostatic properties in β-Thalassemia: the effect of blood transfusion. Blood Transfus. 2017;15(5):413–21..

Agauti I, Cointe S, Robert S, Judicone C, Loundou A, Driss F, et al. Platelet and not erythrocyte microparticles are procoagulant in transfused thalassemia major patients. Br J Haematol. 2015;171(4):615–24.

Nasiri S. An overview on platelet-derived microparticles in platelet concentrates: blood collection, method preparation and storage. IJBC. 2015;7(3):119–28.

Ayers L, Kohler M, Harrison P, Sargent I, Dragovic R, Schaap M, et al. Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay. Thromb Res. 2011;127(4):370–7.

Saleh HA, Kabeer BS. Microparticles: biomarkers and effectors in the cardiovascular system. Global Cardiology Science Practice. 2015;38:1–14.

Ismail EAR, Youssef OI. Platelet-derived microparticles and platelet function profile in children with congenital heart disease. Clin Appl Thromb Hemost. 2013;19(4):424–32.

Bivard A, Lincz LF, Maquire J, Parsons M, Levi C. Platelet microparticles: a biomarker for recanalization in rtPA-treated ischemic stroke patients. Ann Clin Transl Neurol. 2017;4(3):175–9.

Kheansaard W, Phongpao K, Paiboonsukwong K, Pattanapanyasat K, Chaichompoo P, Svasti S. Microparticles from β-thalassemia/HbE patients induce endothelial cell dysfunction. Sci Rep. 2018;8(1):13033.

Elgammal M, Mourad Z, Sadek N, Abassy H, Ibrahim H. Plasma levels of soluble endothelial protein C-receptor in patients with β-thalassemia. Alexandria J Med. 2012;48:283–88.

Chanpeng P, Svasti S, Paiboonsukwong K, Smith DR, Leecharoenkiat K. Platelet proteome reveals specific proteins associated with platelet activation and the hypercoagulable state in β-thalassemia/HbE patients. Sci Rep. 2019;9(1):6059.

Langenskiold C, Mellgreen K, Abrahamsson J, Bemark M. Determination of blood cell subtype concentrations from frozen whole blood samples using trucount beads. Cytometry B Clin Cytom. 2018;94(4):660–6.

Cappellini MD, Musallam KM, Taher AT. Thalassemia as a hypercoagulable state. US Oncology Hematology. 2011;7(2):157–60.

Rubin O, Canellini G, Delobel J, Lion N, Tissot JD. Red blood cell microparticles: clinical relevance. Transfus Med Hemother. 2012;39(5):342–7.

Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarker and beyond. Clin Sci (Lond). 2013;124(7):423–41

Wang CC, Tseng CC, Chang HC, Huang KT, Fang WF, Chen YM, et al. Circulating microparticles are prognostic biomarkers in advanced non-small cell lung cancer patients. Oncotarget. 2017;8(44):75952–67.

Zhou BD, Guo G, Zheng LM, Zu LY, Gao W. Microparticles as novel biomarkers and therapeutic targets in coronary heart disease. Chin Med J (Engl). 2015;128(2):267–72.

Lacroix R, Judicone C, Mooberry M, Boucekine M, Key NS, George FD, et al. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop [published online ahead of print, 2013 Apr 2] [published correction appears in J Thromb Haemost. 2017 Jun;15(6):1236]. J Thromb Haemost. 2013;10.1111/jth.12207.




DOI: https://doi.org/10.15395/mkb.v52n2.1836

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.



 

This Journal indexed by

                    

  


Creative Commons License
MKB is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

 


View My Stats