Skip to main content
Top
Published in: Indian Journal of Pediatrics 3/2019

01-03-2019 | Original Article

Platelet-Derived Microparticles: A New Index of Monitoring Platelet Activation and Inflammation in Kawasaki Disease

Authors: Jing Jin, Jing Wang, Yadong Lu, Zhidan Fan, Na Huang, Le Ma, Haiguo Yu

Published in: Indian Journal of Pediatrics | Issue 3/2019

Login to get access

Abstract

Objective

To investigate the dynamic changes of platelet-derived microparticles (PDMP) in Kawasaki disease (KD) and its clinical significance and to study its relationship with intravenous immunoglobulin (IVIG) resistance, inflammatory indicators and aspirin treatment in children with KD.

Methods

Twenty children with KD were enrolled as the experimental group, while 20 age- and gender-matched children with common febrile disease were included in the control group. Blood samples were drawn before and 7–10 d after IVIG infusion and thereafter at 1, 2, and 3 mo after the onset of KD to estimate the PDMP concentrations by enzyme linked immunosorbent assay (ELISA). C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and cytokines [Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and Soluble interleukin-2 (sIL-2R)] were also measured.

Results

The level of PDMP in KD children before IVIG was significantly higher than that in controls (P < 0.0001). The PDMP level in KD children decreased significantly at 7 to 10 d after IVIG (P < 0.0001) and then decreased to the lowest level in the course of 1 to 2 mo. Some children’s PDMP level rebounded in the course of 3 mo (P = 0.047). In addition, the mean level of PDMP in IVIG-resistant children was higher than that in IVIG-effective children; however, there was no significant difference between the two groups (P = 0.1945). Furthermore, PDMP was positively correlated with hs-CRP, IL-6, and sIL-2R levels, but no correlation was observed with ESR, PCT, and TNF-α levels.

Conclusions

PDMP can be used as an index to monitor inflammation in children at the acute stage of KD. And the duration of platelet activation in KD is individualized.
Literature
3.
go back to reference Lin YJ, Chang JS, Liu X, et al. Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan. Sci Rep. 2015;5:14762.CrossRefPubMedPubMedCentral Lin YJ, Chang JS, Liu X, et al. Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan. Sci Rep. 2015;5:14762.CrossRefPubMedPubMedCentral
4.
go back to reference Li JS, Newburger JW. Antiplatelet therapy in pediatric cardiovascular patients. Pediatr Cardiol. 2010;31:454–61.CrossRefPubMed Li JS, Newburger JW. Antiplatelet therapy in pediatric cardiovascular patients. Pediatr Cardiol. 2010;31:454–61.CrossRefPubMed
5.
go back to reference Tamir A, Sorrentino S, Motahedeh S, et al. The macromolecular architecture of platelet-derived microparticles. J Struct Biol. 2016;193:181–7.CrossRefPubMed Tamir A, Sorrentino S, Motahedeh S, et al. The macromolecular architecture of platelet-derived microparticles. J Struct Biol. 2016;193:181–7.CrossRefPubMed
6.
7.
go back to reference Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2007;21:157–71.CrossRef Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2007;21:157–71.CrossRef
8.
go back to reference Kim HK, Song KS, Chung JH, Lee KR, Lee SN. Platelet microparticles induce angiogenesis in vitro. Br J Haematol. 2004;124:376–84.CrossRefPubMed Kim HK, Song KS, Chung JH, Lee KR, Lee SN. Platelet microparticles induce angiogenesis in vitro. Br J Haematol. 2004;124:376–84.CrossRefPubMed
9.
go back to reference Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension. 2006;48:180–6.CrossRefPubMed Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension. 2006;48:180–6.CrossRefPubMed
10.
go back to reference Preston RA, Jy W, Jimenez JJ, et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003;41:211–7.CrossRefPubMed Preston RA, Jy W, Jimenez JJ, et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003;41:211–7.CrossRefPubMed
11.
go back to reference van der Zee PM, Biro E, Ko Y, et al. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin Chem. 2006;52:657–64.CrossRefPubMed van der Zee PM, Biro E, Ko Y, et al. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin Chem. 2006;52:657–64.CrossRefPubMed
12.
go back to reference Diehl P, Nagy F, Sossong V, et al. Increased levels of circulating microparticles in patients with severe aortic valve stenosis. Thromb Haemost. 2008;99:711–9.CrossRefPubMed Diehl P, Nagy F, Sossong V, et al. Increased levels of circulating microparticles in patients with severe aortic valve stenosis. Thromb Haemost. 2008;99:711–9.CrossRefPubMed
13.
go back to reference Burbano C, Rojas M, Vasquez G, et al. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediat Inflamm. 2015;2015:267590.CrossRef Burbano C, Rojas M, Vasquez G, et al. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediat Inflamm. 2015;2015:267590.CrossRef
14.
go back to reference Singh S, Vignesh P, Burgner D. The epidemiology of Kawasaki disease: a global update. Arch Dis Child. 2015;100:1084–8.CrossRefPubMed Singh S, Vignesh P, Burgner D. The epidemiology of Kawasaki disease: a global update. Arch Dis Child. 2015;100:1084–8.CrossRefPubMed
15.
go back to reference McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–99. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–99.
16.
go back to reference Li ZY, Lou JG, Chen J. Analysis of primary symptoms and disease spectrum in Epstein-Barr virus infected children. Zhonghua Er Ke Za Zhi. 2004;42:20–2.PubMed Li ZY, Lou JG, Chen J. Analysis of primary symptoms and disease spectrum in Epstein-Barr virus infected children. Zhonghua Er Ke Za Zhi. 2004;42:20–2.PubMed
17.
go back to reference Chandrashekar L, Rajappa M, Revathy G, et al. Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis? Clin Chim Acta. 2015;446:181–5.CrossRefPubMed Chandrashekar L, Rajappa M, Revathy G, et al. Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis? Clin Chim Acta. 2015;446:181–5.CrossRefPubMed
18.
go back to reference Hsu J, Gu Y, Tan SL, Narula S, DeMartino JA, Liao C. Bruton's tyrosine kinase mediates platelet receptor-induced generation of microparticles: a potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints. Immunol Lett. 2013;150:97–104.CrossRefPubMed Hsu J, Gu Y, Tan SL, Narula S, DeMartino JA, Liao C. Bruton's tyrosine kinase mediates platelet receptor-induced generation of microparticles: a potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints. Immunol Lett. 2013;150:97–104.CrossRefPubMed
19.
go back to reference Hayon Y, Dashevsky O, Shai E, Brill A, Varon D, R. Leker R. Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia. Curr Neurovasc Res. 2012;9:185–92.CrossRefPubMed Hayon Y, Dashevsky O, Shai E, Brill A, Varon D, R. Leker R. Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia. Curr Neurovasc Res. 2012;9:185–92.CrossRefPubMed
20.
go back to reference Denzer K, Kleijmeer MJ, Heijnen HF, et al. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000;113:3365–74.PubMed Denzer K, Kleijmeer MJ, Heijnen HF, et al. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000;113:3365–74.PubMed
21.
go back to reference Flaumenhaft R, Dilks JR, Richardson J, et al. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood. 2009;113:1112–21.CrossRefPubMedPubMedCentral Flaumenhaft R, Dilks JR, Richardson J, et al. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood. 2009;113:1112–21.CrossRefPubMedPubMedCentral
22.
go back to reference Smalley DM, Root KE, Cho H, Ross MM, Ley K. Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles. Thromb Haemost. 2007;97:67–80.CrossRefPubMed Smalley DM, Root KE, Cho H, Ross MM, Ley K. Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles. Thromb Haemost. 2007;97:67–80.CrossRefPubMed
23.
go back to reference Dean WL, Lee MJ, Cummins TD, Schultz DJ, Powell DW. Proteomic and functional characterisation of platelet microparticle size classes. Thromb Haemost. 2009;102:711–8.CrossRefPubMedPubMedCentral Dean WL, Lee MJ, Cummins TD, Schultz DJ, Powell DW. Proteomic and functional characterisation of platelet microparticle size classes. Thromb Haemost. 2009;102:711–8.CrossRefPubMedPubMedCentral
24.
go back to reference Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007;97:425–34.CrossRefPubMed Sinauridze EI, Kireev DA, Popenko NY, et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007;97:425–34.CrossRefPubMed
25.
go back to reference Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci (Lond). 2013;124:423–41.CrossRef Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci (Lond). 2013;124:423–41.CrossRef
26.
go back to reference Drutskaya MS, Efimov GA, Kruglov AA, Nedospasov SA. Can we design a better anti-cytokine therapy? J Leukoc Biol. 2017;102:783–90.CrossRefPubMed Drutskaya MS, Efimov GA, Kruglov AA, Nedospasov SA. Can we design a better anti-cytokine therapy? J Leukoc Biol. 2017;102:783–90.CrossRefPubMed
27.
go back to reference Larsen SB, Grove EL, Wurtz M, et al. The influence of low-grade inflammation on platelets in patients with stable coronary artery disease. Thromb Haemost. 2015;114:519–29.CrossRefPubMed Larsen SB, Grove EL, Wurtz M, et al. The influence of low-grade inflammation on platelets in patients with stable coronary artery disease. Thromb Haemost. 2015;114:519–29.CrossRefPubMed
28.
go back to reference Kim HJ, Choi EH, Lim YJ, Kil HR. The usefulness of platelet-derived microparticle as biomarker of antiplatelet therapy in Kawasaki disease. J Korean Med Sci. 2017;32:1147–53.CrossRefPubMedPubMedCentral Kim HJ, Choi EH, Lim YJ, Kil HR. The usefulness of platelet-derived microparticle as biomarker of antiplatelet therapy in Kawasaki disease. J Korean Med Sci. 2017;32:1147–53.CrossRefPubMedPubMedCentral
29.
go back to reference Kimura M, Harazaki M, Fukuoka T, et al. Targeted use of prednisolone with the second IVIG dose for refractory Kawasaki disease. Pediatr Int. 2017;59:397–403.CrossRefPubMed Kimura M, Harazaki M, Fukuoka T, et al. Targeted use of prednisolone with the second IVIG dose for refractory Kawasaki disease. Pediatr Int. 2017;59:397–403.CrossRefPubMed
30.
go back to reference Lee HY, Song MS. Predictive factors of resistance to intravenous immunoglobulin and coronary artery lesions in Kawasaki disease. Korean J Pediatr. 2016;59:477–82.CrossRefPubMedPubMedCentral Lee HY, Song MS. Predictive factors of resistance to intravenous immunoglobulin and coronary artery lesions in Kawasaki disease. Korean J Pediatr. 2016;59:477–82.CrossRefPubMedPubMedCentral
31.
go back to reference Seki M, Kobayashi T, Kobayashi T, et al. External validation of a risk score to predict intravenous immunoglobulin resistance in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30:145–7.CrossRefPubMed Seki M, Kobayashi T, Kobayashi T, et al. External validation of a risk score to predict intravenous immunoglobulin resistance in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30:145–7.CrossRefPubMed
32.
go back to reference Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.CrossRefPubMed Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.CrossRefPubMed
33.
go back to reference Yahata T, Suzuki C, Yoshioka A, Hamaoka A, Ikeda K. Platelet activation dynamics evaluated using platelet-derived microparticles in Kawasaki disease. Circ J. 2014;78:188–93.CrossRefPubMed Yahata T, Suzuki C, Yoshioka A, Hamaoka A, Ikeda K. Platelet activation dynamics evaluated using platelet-derived microparticles in Kawasaki disease. Circ J. 2014;78:188–93.CrossRefPubMed
Metadata
Title
Platelet-Derived Microparticles: A New Index of Monitoring Platelet Activation and Inflammation in Kawasaki Disease
Authors
Jing Jin
Jing Wang
Yadong Lu
Zhidan Fan
Na Huang
Le Ma
Haiguo Yu
Publication date
01-03-2019
Publisher
Springer India
Published in
Indian Journal of Pediatrics / Issue 3/2019
Print ISSN: 0019-5456
Electronic ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2765-2

Other articles of this Issue 3/2019

Indian Journal of Pediatrics 3/2019 Go to the issue