Circulating microparticles and thrombin generation in patients with Chronic Lymphocytic Leukemia

Authors

  • Fernanda Cristina Gontijo Evangelista Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Aline Lúcia Menezes Ferrão Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Rita Carolina Figueiredo Duarte Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Lorena Caixeta Gomes Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Luan Carlos Vieira Alves Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil https://orcid.org/0000-0002-9024-8872
  • Fernanda Freire Nunes Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Tatiane Vieira Braga Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Marie Gabriele Santiago Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Sergio Schusterschitz da Silva Araújo Clinical Hospital, Federal University of Minas Gerais, Minas Gerais, Brazil
  • Maria das Graças Carvalho Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil https://orcid.org/0000-0002-1669-3302
  • Adriano Sabino Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Minas Gerais, Brazil https://orcid.org/0000-0001-8562-8689

DOI:

https://doi.org/10.1590/s2175-97902022e19407%20

Keywords:

Chronic lymphocytic leukemia, Prognosis, Microparticles, Thrombin Generation

Abstract

Chronic Lymphocytic Leukemia (CLL) has shown great biological heterogeneity, with a variable prognosis, and a short survival in some patients. In this light, the present study focused on the prognostic utility of circulating microparticles (MPs) and a Thrombin Generation (TG) Profile for thrombotic risk and disease progression in CLL patients. Circulating microparticles and TG were evaluated in 35 patients with CLL and 35 healthy individuals. For circulating microparticles, significant differences were observed among the following groups: MPs derived from endothelial cells (p = 0.002), B lymphocytes (p < 0.001), platelets (p = 0.003), and Tissue Factor MPs in monocytes (p < 0.001). In all cases, MP values were higher for the CLL group. When compared to the controls, CLL patients presented a decrease in TG, characterized by a reduced endogen thrombin potential (ETP) (p = 0.031). When the results were analyzed according to the Binet stage, as compared to the controls, the Binet B+C group also presented lower ETP values (p = 0.009). No significant differences were observed between the control and the Binet A groups or between the Binet A and the Binet B + C groups. Although hemostatic alterations may occur in patients with CLL, these parameters do not seem to be useful to indicate disease progression.

Downloads

Download data is not yet available.

References

Aguirre Palma LM, Flamme H, Gerke I, Kreuzer KA. Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro. Cancer Microenviron. 2016;9(1):13-26.

Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, Vaugier G, Potron G, Colona P, Oberking F, Thomas M, Tchernia G, Jacquillat C, Boivin P, Lesty C, Duault MT, Monconduit M, Belabbes S, Gremy F. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206.

Boccaccio C, Comoglio PM. Genetic link between cancer and thrombosis. J Clin Oncol. 2009;27(29):4827-4833.

Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014;21(1):15-25.

Campos FM, Franklin BS, Teixeira-Carvalho A, Filho AL, de Paula SC, Fontes CJ, et al. Augmented plasma microparticles during acute Plasmodium vivax infection. Malar J. 2010;9:327.

Castoldi E, Rosing J. Thrombin generation tests. Thromb Res. 2011;127(3):S21-25.

Danilov A, Danilova O, Klein A, Huber B. Molecular pathogenesis of chronic lymphocytic leukemia. Curr Mol Med. 2006;6(6):665-675.

Dighiero G. CLL biology and prognosis. Hematology Am Soc Hematol Educ Program. 2005;(1):278-284.

Domnikova NP, Dolgikh TY, Sholenberg E V, Vorontsova EV, Goreva OB, Mel’nikova EV, et al. Blood microvesicles during chronic lymphoproliferative diseases. Bull Exp Biol Med. 2013;156(1):94-97.

Duarte RCF, Gonçalves LH, Campos FMF, Filho OAM, Alves MT, Fernandes AP, et al. Effect of acetylsalicylic acid on platelet activation and oxidative profile in a set of Brazilian patients with type 2 diabetes mellitus. Blood Coagul Fibrinolysis. 2015;26(2):123-130.

Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: Biological and clinical aspects. J Thromb Haemost. 2013;11(2):223-233.

Gade IL, Riddersholm SJ, Christiansen I, Rewes A, Frederiksen M, Enggaard L, et al. Venous thromboembolism in chronic lymphocytic leukemia: a Danish nationwide cohort study. Blood Adv. 2018;2(21):3025-3034.

Ghosh AK, Secreto CR, Knox TR, Ding W, Mukhopadhyay D, Kay NE. Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood. 2010;115(9):1755-1764.

Goede V, Klein C, Stilgenbauer S. Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin’s lymphomas: a glycoengineered type II CD20 antibody. Oncol Res Treat. 2015;38(4):185-192.

Helbing T, Olivier C, Bode C, Moser M, Diehl P. Role of microparticles in endothelial dysfunction and arterial hypertension. World J Cardiol. 2014;6(11):1135-1139.

Hemker HC, Giesen P, Al Dieri R, Regnault V, De Smedt E, Wagenvoord R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003;33(1):4-15.

Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz- krzemien S, Kuliczkowski K, et al. Cladribine, But Not Fludarabine, Added to Daunorubicin and Cytarabine During Induction Prolongs Survival of Patients With Acute Myeloid Leukemia: A Multicenter, Randomized Phase III Study. J Clin Oncol . 2012;30(20):2441-2448.

Krause G, Baki I, Kerwien S, Knödgen E, Neumann L, Göckeritz E, et al. Cytotoxicity of the CD37 antibody BI 836826 against chronic lymphocytic leukaemia cells in combination with chemotherapeutic agents or PI3K inhibitors. Br J Haematol. 2016;173(5):791-794.

Lemanne D, Block KI, Kressel BR, Sukhatme VP, White JD. A Case of complete and durable molecular remission of chronic lymphocytic leukemia following treatment with epigallocatechin-3-gallate, an extract of green tea. Cureus. 2015;7(12):e441.

Lukenbill J, Kalaycio M. Fludarabine: A review of the clear benefits and potential harms. Leuk Res. 2013;37(9):986-994.

Martinez-Torres AC, Quiney C, Attout T, Boullet H, Herbi L, Vela L, et al. CD47 Agonist Peptides Induce Programmed Cell Death in Refractory Chronic Lymphocytic Leukemia B Cells via PLCγ1 Activation: Evidence from Mice and Humans. PLoS Med. 2015;12(3):e1001796.

Palanca-Wessels MCA, Czuczman M, Salles G, Assouline S, Sehn LH, Flinn I, et al. Safety and activity of the anti- CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: A phase 1 study. Lancet Oncol. 2015;16(6):704-715.

Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46(2):219-34.

Sagatys EM, Zhang L. Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia. Cancer Control. 2012;19(1):18-25.

Šimkovič M, Vodárek P, Motyčková M, Belada D, Vrbacký F, Žák P, et al. Venous thromboembolism in patients with chronic lymphocytic leukemia. Thromb Res. 2015;136(6):1082-1086.

Systat Software I. Sigma Stat version 2.03. 2013.

Trappenburg MC, Van Schilfgaarde M, Marchetti M, Spronk HM, Ten Cate H, Leyte A, et al. Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia. Haematologica. 2009;94(7):911- 918.

Vasilatou D, Papageorgiou SG, Dimitriadis G, Pappa V. Epigenetic alterations and microRNAs New players in the pathogenesis of myelodysplastic syndromes. Epigenetics. 2013;8(6):561-570.

Voloshin T, Fremder E, Shaked Y. Small but mighty: Microparticles as mediators of tumor progression. Cancer Microenviron . 2014;7(1-2):11-21.

Wiestner A. The role of b-cell receptor inhibitors in the treatment of patients with chronic lymphocytic leukemia. Haematologica . 2015;100(12):1495-1507.

Wu YY, Tang L, Wang MH. Leukemia and rick of venous thromboembolism: A Meta-analysis and systematic review of 144 studies comprising 162, 126 patients. Sci Rep. 2017;7(1):1167.

Young A, Chapman O, Connor C, Poole C, Rose P, Kakkar AK. Thrombosis and cancer. Nat Rev Clin Oncol. 2012;9(8):437-449.

Yu JL, May L, Lhotak V, Shahrzad S, Shirasawa S, Weitz JI, et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood . 2005;105(4):1734-1741.

Yu L, Kim H, Kasar SN, Benien P, Du W, Hoang K, et al. Survival of Del17p CLL depends on genomic complexity and somatic mutation. Clin Cancer Res. 2016;23(3):735-745.

Yuana Y, Sturk A, Nieuwland R. Extracellular vesicles in physiological and pathological conditions. Blood Rev. 2013;27(1):31-39.

Downloads

Published

2022-12-19

Issue

Section

Original Article

How to Cite

Circulating microparticles and thrombin generation in patients with Chronic Lymphocytic Leukemia. (2022). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e19407