Platelet function alterations in dengue are associated with plasma leakage

• DOI: 10.1160/th14-01-0056
• Publication Date: 2014-04-03T07:40:32Z
• Authors: Bachti Alisjahbana; Philip G. de Groot; Agnes R. Indrati; Rob Fijnheer; Mita Puspita; Intan M. W. Dewi; Lisa van de Wijer; Ellen M. S. de Boer; Mark Roest; André J. A. M. va...; Quirijn de Mast; Meta Michels
• Keywords: Adult; Blood Platelets; Male; 0301 basic medicine; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Capillary Permeability; Dengue; 03 medical and health sciences; Leukocytes; Odds Ratio; Humans; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Chi-Square Distribution; Flow Cytometry; Platelet Activation; 3. Good health; P-Selectin; Indonesia; Acute Disease; Linear Models; Female; Receptors, Thrombin; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Biomarkers

SummarySevere 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.