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Thromb Haemost 2014; 112(02): 352-362
DOI: 10.1160/TH14-01-0056
Wound Healing and Inflammation/Infection
Schattauer GmbH

Platelet function alterations in dengue are associated with plasma leakage

Meta Michels
1   Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
,
Bachti Alisjahbana
2   Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia
,
Philip G. de Groot
3   Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Agnes R. Indrati
4   Department of Clinical Pathology, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia
,
Rob Fijnheer
3   Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Mita Puspita
2   Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia
,
Intan M. W. Dewi
2   Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia
,
Lisa van de Wijer
1   Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
,
Ellen M. S. de Boer
1   Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
,
Mark Roest
3   Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
,
André J. A. M. van der Ven
1   Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
,
Quirijn de Mast
1   Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
› Author Affiliations Financial support: MM was funded by a Junior Research Grant provided by the Radboud University Medical Center, Nijmegen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Further Information

Publication History

Received: 19 January 2014

Accepted after major revision: 07 March 2014

Publication Date:
04 December 2017 (online)

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Summary

Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometerbased assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (αIIbβ3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated αIIbβ3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated αIIbβ3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3–22.7) and 3.9 (95% CI 1.1–13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.

Keywords

Dengue virus infection - platelet function - flow cytometry - plasma leakage - serotonin
 

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