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


ERC Consolidator Grant for Bousema and Sechopoulos

12 December 2019

Teun Bousema and Ioannis Sechopoulos are to receive an ERC Consolidator Grant of around two million euros each. This European research subsidy will enable them to carry out research for the next five years.

read more

'Stofwisselkracht' grant for Paola de Haas and Alessandra Cambi

5 December 2019

Paola de Haas and Alessandra Cambi, theme Nanomedicine, have recently been awarded a grant from ‘Stichting Stofwisselkracht’ for their project entitled “Identification of immune-related symptoms in Congenital Disorders of Glycosylation”.

read more

Newly appointed Principal Clinicians RIHS 2020 - 2022

5 December 2019

These caregivers are at the forefront of renewing patient care and take the lead in the development and realization of the Radboud vision.

read more

Call for nominations RIHS Awards 2019

4 December 2019

RIHS researchers are invited to propose candidates for the RIHS PhD Award, the Societal Impact Award, the Science Award and the Supervisor of the year Award. Deadline for nominations is 13 January 2020.

read more

Newly appointed Junior Principal Clinicians

3 December 2019

The appointed junior Principal Clinician for RIMLS are Heidi Zweers-van Essen and Jenneke Leentjens. These caregivers are at the forefront of renewing patient care and take the lead in the development and realization of the Radboudumc vision.

read more

Large research grant for Radboudumc Health Academy & HAN

3 December 2019

The Radboudumc Health Academy and the HAN receive a large research grant of 875.000 euro from the NRO (Nationaal Regieorgaan voor Onderwijsonderzoek) on developing flexible expertise.

read more