Point-of-care thrombocyte function testing using multiple-electrode aggregometry in dengue patients: an explorative study

Wesley De Jong,Usman Hadi,Musofa Rusli,Inge Verbeek,Eric Van Gorp,Tri Pudy Asmarawati,Marco Goeijenbier

doi:10.1186/s12879-020-05248-4

Wesley De Jong, Usman Hadi + Show 5 more

Open Access

https://doi.org/10.1186/s12879-020-05248-4

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Abstract

BackgroundDengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage.MethodsIn this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC).ResultsA total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases.ConclusionThrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.

Highlights

Dengue virus (DENV), most likely the most important mosquito transmitted viral disease in the world, is endemic in South East Asia
Exclusion criteria were a thrombocyte count below 100 × 109/ L and the use of any medication with a anticoagulant and/or antiplatelet effect, including nonsteroidal antiinflammatory drugs (NSAIDs), acetyl salicylic acid (ASA), non-vitamin K oral anticoagulants (NOAC), direct oral anticoagulants (DOAC) and antiplatelet drugs such as clopidogrel, dipyridamole or vitamin K antagonists
To the best of our knowledge this is the first study that has applied short-turnaround time thrombocyte aggregation tests in acute DENV cases. This explorative data contributes to the understanding of thrombopathies as result of a DENV infection and we suggest that thrombocyte aggregation tests, such as the MultiPlate, could be further studied in the clinical assessment of DENV-suspected patients

Summary

Introduction

Dengue virus (DENV), most likely the most important mosquito transmitted viral disease in the world, is endemic in South East Asia. Earlier studies tried to identify patients at risk of developing severe dengue by specific biomarkers, genomics, machine learning and early point-ofcare ultrasound. Many of these promising markers call for difficult, expensive or laborious techniques that are not practical in the current Indonesian healthcare setting [7,8,9,10]. It is difficult to early differentiate uncomplicated dengue from those that will develop a severe form of the disease that warrants intensified in-hospital monitoring Such approaches were previously studied in a specific combination of hematological parameters to differentiate between dengue and malaria in Thailand [11]. We investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using MultiplateTM multipleelectrode aggregometry to explore its potential in triage

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