Open AccessPlatelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria
Author(s) -
João Conrado Khouri Dos-Santos,
João Luiz Silva-Filho,
Carla C. Judice,
Ana Carolina Andrade Vitor Kayano,
Júlio Aliberti,
Ricardo Khouri,
Diógenes Saulo de Lima,
Helder I. Nakaya,
Marcus Vinícius Guimarães Lacerda,
Erich Vinícius De Paula,
Stefanie Costa Pinto Lopes,
Fábio Trindade Maranhão Costa
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0007656
Subject(s) - platelet , platelet activation , von willebrand factor , endothelial activation , plasmodium vivax , malaria , immunology , mean platelet volume , flow cytometry , p selectin , medicine , biology , plasmodium falciparum , inflammation
Platelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness. We performed platelet flow cytometry of PAC-1 and P-selectin. We measured platelet markers (CXCL4, CD40L, P-selectin, Thrombopoietin, IL-11) and endothelial activation markers (ICAM-1, von Willebrand Factor and E-selectin) in plasma with a multiplex-based assay. The values of each mediator were used to generate heatmaps, K-means clustering and Principal Component analysis. In addition, we determined pair-wise Pearson’s correlation coefficients to generate correlation networks. Platelet counts were reduced, and mean platelet volume increased in malaria patients. The activation of circulating platelets in flow cytometry did not differ between patients and controls. CD40L levels (Median [IQ]: 517 [406–651] vs. 1029 [732–1267] pg/mL, P = 0.0001) were significantly higher in patients, while P-selectin and CXCL4 showed a nonsignificant trend towards higher levels in patients. The network correlation approach demonstrated the correlation between markers of platelet and endothelial activation, and the heatmaps revealed a distinct pattern of activation in two subsets of P . vivax patients when compared to controls. Although absolute platelet activation was not strong in uncomplicated vivax malaria, markers of platelet activity and production were correlated with higher endothelial cell activation, especially in a specific subset of patients.