Original Article

Correlations Between the Circulating Level of Cell-Derived Microparticles and Surgical Variables in Heart Valve Surgery with Cardiopulmonary Bypass

Abstract

Background: Cell-derived microparticles (MPs) as membrane vesicles are procoagulant. They play a role in surgical hemostasis. In this study, the correlations between the circulating level of cell-derived MPs and surgical variables in heart valve surgery were investigated.

Methods: The present prospective case-series study was conducted in Rajaie Cardiovascular Medical and Research Center from January through March 2021. Forty patients undergoing heart valve surgery with cardiopulmonary bypass (CPB) were enrolled. Before the induction of anesthesia and 30 minutes after the administration of protamine sulfate, venous blood samples were collected. After MP isolation, the concentration of MPs was determined via the Bradford method. Flow cytometry analysis was performed to determine the MP count and phenotype. Intraoperative variables and postoperative routine coagulation tests were defined as surgical variables. Postoperative coagulopathy was defined as an activated partial thromboplastin time (aPTT) ≥48 seconds or an international normalized ratio (INR) >1.5.

Results: The total concentration of MPs and the MP count increased significantly after surgery compared with before surgery. The postoperative concentration of MPs was positively correlated with the CPB time (P=0.030, ρ=0.40). The preoperative concentration of MPs was significantly lower in patients with higher postoperative aPTT and INR (P=0.003, Ρ= −0.50 and P=0.020, Ρ= −0.40, respectively). In multivariate logistic regression analysis, the preoperative MP concentration (OR, 1.00; 95% CI, 1.00 to 1.01; P=0.017) was considered a risk factor for postoperative coagulopathy.

Conclusion: The levels of MPs, especially platelet-derived MPs, rose after surgery, in correlation with the CPB time. Given the role of MPs in the induction of coagulation and inflammation, they can be considered therapeutic goals for preventing postoperative complications. In addition, the preoperative levels of MPs are a risk factor for predicting the occurrence of postoperative coagulopathy in heart valve surgery.

1. Morel O, Jesel L, Freyssinet JM, Toti F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 2011;31:15-26.
2. Xie RF, Hu P, Li W, Ren YN, Yang J, Yang YM, Wang ZY, Fan HH. The effect of platelet-derived microparticles in stored apheresis platelet concentrates on polymorphonuclear leucocyte respiratory burst. Vox Sang 2014;106:234-241.
3. Perez-Pujol S, Marker PH, Key NS. Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer. Cytometry A 2007;71:38-45.
4. Butenas S, Orfeo T, Mann KG. Tissue factor in coagulation: Which? Where? When? Arterioscler Thromb Vasc Biol 2009;29:1989-1996.
5. Fu L, Hu XX, Lin ZB, Chang FJ, Ou ZJ, Wang ZP, Ou JS. Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation. J Thorac Cardiovasc Surg 2015;150:666-672.
6. Lin ZB, Ci HB, Li Y, Cheng TP, Liu DH, Wang YS, Xu J, Yuan HX, Li HM, Chen J, Zhou L, Wang ZP, Zhang X, Ou ZJ, Ou JS. Endothelial microparticles are increased in congenital heart diseases and contribute to endothelial dysfunction. J Transl Med 2017;15:4.
7. . Olatunya OS, Lanaro C, Longhini AL, Penteado CFF, Fertrin KY, Adekile A, Saad STO, Costa FF. Red blood cells microparticles are associated with hemolysis markers and may contribute to clinical events among sickle cell disease patients. Ann Hematol 2019;98:2507-2521.
8. Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci (Lond) 2013;124:423-441.
9. Berezin AE. Microparticles in Chronic Heart Failure. Adv Clin Chem 2017;81:1-41.
10. Li Y, Yuan H, Chen C, Chen C, Ma J, Chen Y, Li Y, Jian Y, Liu D, Ou Z, Ou J. Concentration of circulating microparticles: a new biomarker of acute heart failure after cardiac surgery with cardiopulmonary bypass. Sci China Life Sci 2021;64:107-116.
11. Ma J, Yuan HX, Chen YT, Ning DS, Liu XJ, Peng YM, Chen C, Song YK, Jian YP, Li Y, Liu Z, Ou ZJ, Ou JS. Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass. Ann Transl Med 2021;9:786.
12. Vuylsteke A, Pagel C, Gerrard C, Reddy B, Nashef S, Aldam P, Utley M. The Papworth Bleeding Risk Score: a stratification scheme for identifying cardiac surgery patients at risk of excessive early postoperative bleeding. Eur J Cardiothorac Surg 2011;39:924-930.
13. Matijevic N, Wang YW, Wade CE, Holcomb JB, Cotton BA, Schreiber MA, Muskat P, Fox EE, Del Junco DJ, Cardenas JC, Rahbar MH, Cohen MJ; PROMMTT Study Group. Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study: correlation with coagulopathy. Thromb Res 2014;134:652-658.
14. Hashemi Tayer A, Amirizadeh N, Ahmadinejad M, Nikougoftar M, Deyhim MR, Zolfaghari S. Procoagulant Activity of Red Blood Cell-Derived Microvesicles during Red Cell Storage. Transfus Med Hemother 2019;46:224-230.
15. Rubin O, Canellini G, Delobel J, Lion N, Tissot JD. Red blood cell microparticles: clinical relevance. Transfus Med Hemother 2012;39:342-347.
16. Kielkopf CL, Bauer W, Urbatsch IL. Bradford Assay for Determining Protein Concentration. Cold Spring Harb Protoc 2020;2020:102269.
17. Nishiguchi K, Okuda J, Toyoda M, Tanaka K, Tanigawa N. Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma. Dis Colon Rectum. 2001;44:223-230.
18. Leung KL, Lai PB, Ho RL, Meng WC, Yiu RY, Lee JF, Lau WY. Systemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma: A prospective randomized trial. Ann Surg 2000;231:506-511.
19. Ikeda M, Iwamoto Si, Imamura H, Furukawa H, Kawasaki T. Increased platelet aggregation and production of platelet-derived microparticles after surgery for upper gastrointestinal malignancy. J Surg Res 2003;115:174-183.
20. Park MS, Owen BA, Ballinger BA, Sarr MG, Schiller HJ, Zietlow SP, Jenkins DH, Ereth MH, Owen WG, Heit JA. Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not. Surgery 2012;151:831-836.
21. Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC, Maquelin KN, Roozendaal KJ, Jansen PG, ten Have K, Eijsman L, Hack CE, Sturk A. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997;96:3534-3541.
22. Craver JM, Cohen C, Weintraub WS. Case-matched comparison of mitral valve replacement and repair. Ann Thorac Surg 1990;49:964-969.
23. Jy W, Ricci M, Shariatmadar S, Gomez-Marin O, Horstman LH, Ahn YS. Microparticles in stored red blood cells as potential mediators of transfusion complications. Transfusion 2011;51:886-893.
24. Kozuma Y, Sawahata Y, Takei Y, Chiba S, Ninomiya H. Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol 2011;152:631-639.
25. Nantakomol D, Dondorp AM, Krudsood S, Udomsangpetch R, Pattanapanyasat K, Combes V, Grau GE, White NJ, Viriyavejakul P, Day NP, Chotivanich K. Circulating red cell-derived microparticles in human malaria. J Infect Dis 2011;203:700-706.
26. Rubin O, Delobel J, Prudent M, Lion N, Kohl K, Tucker EI, Tissot JD, Angelillo-Scherrer A. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation. Transfusion 2013;53:1744-1754.
27. Diehl P, Aleker M, Helbing T, Sossong V, Beyersdorf F, Olschewski M, Bode C, Moser M. Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activation. Interact Cardiovasc Thorac Surg 2010;11:133-137.
28. Ay C, Freyssinet JM, Sailer T, Vormittag R, Pabinger I. Circulating procoagulant microparticles in patients with venous thromboembolism. Thromb Res 2009 Mar;123:724-726.
29. Bucciarelli P, Martinelli I, Artoni A, Passamonti SM, Previtali E, Merati G, Tripodi A, Mannucci PM. Circulating microparticles and risk of venous thromboembolism. Thromb Res. 2012;129:591-597.
30. Macey MG, Enniks N, Bevan S. Flow cytometric analysis of microparticle phenotype and their role in thrombin generation. Cytometry B Clin Cytom 2011;80:57-63.
31. Castaman G, Yu-Feng L, Battistin E, Rodeghiero F. Characterization of a novel bleeding disorder with isolated prolonged bleeding time and deficiency of platelet microvesicle generation. Br J Haematol 1997;96:458-63.
32. Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 1989;264:17049-17057.
33. Jy W, Horstman LL, Arce M, Ahn YS. Clinical significance of platelet microparticles in autoimmune thrombocytopenias. J Lab Clin Med 1992;119:334-345.
34. Herring JM, McMichael MA, Smith SA. Microparticles in health and disease. J Vet Intern Med 2013;27:1020-1033.
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IssueVol 17 No 3 (2022): J Teh Univ Heart Ctr QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jthc.v17i3.10846
Keywords
Cell-derived microparticles Heart valve disease Cardiac surgical procedure

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1.
Abdolalian M, Khalaf-Adeli E, Yari F, Hosseini S, Bakhshandeh H. Correlations Between the Circulating Level of Cell-Derived Microparticles and Surgical Variables in Heart Valve Surgery with Cardiopulmonary Bypass. J Tehran Heart Cent. 2022;17(3):134-139.