23 April 2019

In the PLoS Pathogens Quirijn de Mast and his colleagues from the theme Infectious diseases and global health, showed that excessive binding of the coagulation protein von Willebrand factor leads to removal of sialic acid from platelets and platelet clearance.

Abstract
Thrombocytopenia and platelet dysfunction are commonly observed in patients with dengue virus (DENV) infection and may contribute to complications such as bleeding and plasma leakage. The etiology of dengue-associated thrombocytopenia is multifactorial and includes increased platelet clearance. The binding of the coagulation protein von Willebrand factor (VWF) to the platelet membrane and removal of sialic acid (desialylation) are two well-known mechanisms of platelet clearance, but whether these conditions also contribute to thrombocytopenia in dengue infection is unknown. In two observational cohort studies in Bandung and Jepara, Indonesia, we show that adult patients with dengue not only had higher plasma concentrations of plasma VWF antigen and active VWF, but that circulating platelets had also bound more VWF to their membrane. The amount of platelet-VWF binding correlated well with platelet count. Furthermore, sialic acid levels in dengue patients were significantly reduced as assessed by the binding of Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL-II) to platelets. Sialic acid on the platelet membrane is neuraminidase-labile, but dengue virus has no known neuraminidase activity. Indeed, no detectable activity of neuraminidase was present in plasma of dengue patients and no desialylation was found of plasma transferrin. Platelet sialylation was also not altered by in vitro exposure of platelets to DENV nonstructural protein 1 or cultured DENV. In contrast, induction of binding of VWF to glycoprotein 1b on platelets using the VWF-activating protein ristocetin resulted in the removal of platelet sialic acid by translocation of platelet neuraminidase to the platelet surface. The neuraminidase inhibitor oseltamivir reduced VWF-induced platelet desialylation. Our data demonstrate that excessive binding of VWF to platelets in dengue results in neuraminidase-mediated platelet desialylation and platelet clearance. Oseltamivir might be a novel treatment option for severe thrombocytopenia in dengue infection.
 
Publication
Desialylation of platelets induced by Von Willebrand Factor is a novel mechanism of platelet clearance in dengue.
Riswari SF, Tunjungputri RN, Kullaya V, Garishah FM, Utari GSR, Farhanah N, Overheul GJ, Alisjahbana B, Gasem MH, Urbanus RT, de Groot PG, Lefeber DJ, van Rij RP, van der Ven A, de Mast Q.

Quirijn de Mast is member of the theme Infectious diseases and global health.

Related news items


Rob ter Horst in Dutch television broadcast Brandpunt Plus

21 May 2019

In a Dutch television broadcast, called Brandpunt Plus, Rob ter Horst, PhD candidate, theme Infectious diseases and global health, explains how he records data about himself and what he hopes to find out about himself.

read more

How do we keep new technology affordable to improve the lives of people?

16 May 2019

Improving healthcare by means of new technological developments? We need to change the entire approach for evaluating the true impact , says Maroeska Rovers. By bringing together all stakeholders from the beginning, millions of euros can be saved.

read more

Join the Young Academy of Europe

15 May 2019

The YAE is a pan-European initiative of outstanding young researchers, from all fields, for networking, scientific exchange and science policy.

read more

Algorithm calculates the presence and aggressiveness of prostate tumors

14 May 2019

A computer program that analyzes MRI images can reliably map the presence and even the aggressiveness of a prostate tumor. This is what Radboudumc researchers and international colleagues have published in the scientific journal Investigative Radiology.

read more

Universal tumor BRCA1/2 testing of ovarian cancer

13 May 2019

Marjolijn Ligtenberg, Janet Vos and Nicoline Hoogerbrugge, assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as prescreen for PARPi treatment and cancer predisposition testing. They have published their findings in the JNCI.

read more

Association of gestational weight gain with adverse maternal and infant outcomes

13 May 2019

An individual participant meta-analysis published in JAMA showed that pregnancy BMI is related stronger to maternal and infant complications than to gestational weight gain. The PRIDE Study, with coauthors Marleen van Gelder and Nel Roeleveld, was one of the participating cohorts.

read more