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

Abstract

Background Dengue 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. Methods In 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). Results A 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. Conclusion Thrombocyte 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.

Thrombocytopenia in Virus Infections

“…Activated platelets undergo degranulation, attach themselves to the vascular wall and form thrombi, effectively removing them from the circulation, which results in thrombocytopenia. Despite this activation, platelets from dengue patients are hyporesponsive to procoagulant stimuli in aggregometry assays, which is likely the result of exhaustion [ 65 ]. This illustrates thrombocytopenia and platelet dysfunction go hand in hand during DENV infection.…”

Rotational thromboelastometry in critical phase of dengue infection: Association with bleeding

“…Further clinical correlation demonstrated that lower AUC may indicate the severity of the disease and may correlate with the duration of the hospital stay. 17 In the context of other viral hemorrhagic fevers such as Crimean‐Congo hemorrhagic fever, Lassa fever, and Argentinian hemorrhagic fever, platelet aggregometry studies have suggested that the coagulopathy is clearly due to defects in platelet function and aggregation. 18 , 19 The findings of the study on Crimean‐ Congo hemorrhagic fever found that mucosal bleeding was not due to thrombocytopenia but rather due to platelet dysfunction in aggregation.…”

“…Interestingly, the investigators of the above study did not find any correlation between platelet count and platelet aggregation/AUC. Further clinical correlation demonstrated that lower AUC may indicate the severity of the disease and may correlate with the duration of the hospital stay 17 . In the context of other viral hemorrhagic fevers such as Crimean‐Congo hemorrhagic fever, Lassa fever, and Argentinian hemorrhagic fever, platelet aggregometry studies have suggested that the coagulopathy is clearly due to defects in platelet function and aggregation 18,19 .…”

Internet of medical things (IoMT)-integrated biosensors for point-of-care testing of infectious diseases

“…In this matter, POCT devices detecting platelet aggregation has been developed. Multiplate™ multiple-electrode biosensor potential was evaluated for platelet aggregation ( De Jong et al, 2020 ). Platelets become adhesive upon activation with reagents and got deposited onto the metal sensor wires that led to increase in electrical resistance.…”