Abstract
Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections.
Highlights
Linked with platelet destruction and thrombocytopenia in these patients[14,15,16]
To elucidate the association between thrombocytopenia and activation status of platelets in peripheral blood of the dengue patients, the platelet counts along with platelet surface activation markers such as P selectin and PS expression, and PAC1 binding were measured at various days of fever
With a focus on investigating the various mechanisms of thrombocytopenia in dengue infection, we described from this study: 1) the activation status of platelets was a crucial cause of their depletion from circulation in patients with Dengue virus (DENV) infections and 2) the mechanism of platelet depletion included processes such as lysis, aggregation and clot formation and phagocytosis of platelets
Summary
Linked with platelet destruction and thrombocytopenia in these patients[14,15,16]. Further an ex vivo report describes a direct correlation between microparticles (MPs) derived from activated platelets in the peripheral blood and the severity of thrombocytopenia in dengue patients[17]. DENV infects circulating platelets and their progenitor megakaryocytes in bone marrow[19,20] It interacts with platelets and megakaryocytes via the cell surface receptor FcγRII21. Our data showed that circulating platelets carrying high copy numbers of DENV genome were hyperactive expressing elevated P-selectin and binding of PAC-1 (activation-dependent antibody) on surface and generating MPs (well known makers of platelet activation)[12,13,24]. These activated platelets displayed elevated levels of surface bound C3 and IgG. We observed that the DENV-mediated activation of platelets was significantly abrogated in the presence of platelet activation inhibitor such as prostacyclin (PGI2)
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