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

Publisher: BioMed Central Country of Publication: England NLM ID: 100968551 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2334 (Electronic) Linking ISSN: 14712334 NLM ISO Abbreviation: BMC Infect Dis Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Point-of-Care Systems* ; Point-of-Care Testing*; Blood Platelets/*metabolism ; Dengue/*diagnosis ; Dengue/*epidemiology ; Dengue Virus/*immunology; Adenosine Diphosphate/blood ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Collagen/metabolism ; Dengue/virology ; Enzyme-Linked Immunosorbent Assay ; Female ; Fever/diagnosis ; Humans ; Indonesia/epidemiology ; Male ; Middle Aged ; Peptide Fragments/blood ; Platelet Aggregation ; Platelet Count ; Prospective Studies ; Severity of Illness Index ; Young Adult

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.

J Clin Microbiol. 2016 Aug;54(8):2090-5. (PMID: 27225409)
Ann Clin Microbiol Antimicrob. 2019 Mar 13;18(1):10. (PMID: 30871553)
Infect Dis Poverty. 2017 Mar 2;6(1):27. (PMID: 28249623)
Antiviral Res. 2013 May;98(2):192-208. (PMID: 23523765)
IEEE Trans Biomed Eng. 2019 Oct;66(10):2861-2868. (PMID: 30716030)
Sci Rep. 2018 Jun 26;8(1):9700. (PMID: 29946074)
N Engl J Med. 2007 Dec 13;357(24):2482-94. (PMID: 18077812)
Crit Rev Microbiol. 2018 Aug;44(4):487-503. (PMID: 29451044)
Virus Res. 2019 Jan 15;260:163-172. (PMID: 30282001)
Thromb Res. 2015 Dec;136(6):1126-32. (PMID: 26462407)
PLoS One. 2018 Nov 9;13(11):e0206346. (PMID: 30412591)
Cell Rep. 2019 Jan 29;26(5):1104-1111.e4. (PMID: 30699342)
PLoS Negl Trop Dis. 2019 Jan 10;13(1):e0007038. (PMID: 30629593)
Platelets. 2019;30(1):81-87. (PMID: 29135309)
Am J Clin Pathol. 2014 Nov;142(5):647-56. (PMID: 25319980)
Front Immunol. 2019 Sep 13;10:2204. (PMID: 31572400)
Platelets. 2017 Nov;28(7):724-727. (PMID: 28287000)
PLoS Negl Trop Dis. 2011 Jul;5(7):e1244. (PMID: 21811645)
PLoS One. 2017 Jun 2;12(6):e0178443. (PMID: 28575000)
Front Immunol. 2014 Dec 18;5:649. (PMID: 25566260)
PLoS Negl Trop Dis. 2019 Oct 21;13(10):e0007785. (PMID: 31634352)
Eur J Clin Microbiol Infect Dis. 2017 Dec;36(12):2503-2512. (PMID: 28840345)
Eur J Haematol. 2015 Feb;94(2):138-44. (PMID: 24981148)
Sci Rep. 2017 Jul 25;7(1):6354. (PMID: 28743915)
PLoS Negl Trop Dis. 2013;7(2):e2055. (PMID: 23437406)
J Cardiovasc Pharmacol. 2019 Jan;73(1):40-47. (PMID: 30383606)
Crit Rev Biochem Mol Biol. 1997;32(6):437-502. (PMID: 9444477)
J Immunol. 2014 Aug 15;193(4):1864-72. (PMID: 25015827)
Southeast Asian J Trop Med Public Health. 2014 Jan;45(1):53-61. (PMID: 24964654)
Infect Genet Evol. 2015 Jun;32:165-77. (PMID: 25784569)
N Engl J Med. 2005 Sep 1;353(9):877-89. (PMID: 16135832)
Am J Trop Med Hyg. 2014 Sep;91(3):621-634. (PMID: 24957540)
Sci Rep. 2017 Jan 31;7:41697. (PMID: 28139770)
Semin Thromb Hemost. 2018 Oct;44(7):683-690. (PMID: 29913535)
PLoS Negl Trop Dis. 2010 Jul 06;4(7):e738. (PMID: 20625558)
J Biomed Sci. 2018 Jul 24;25(1):58. (PMID: 30037331)
Front Med (Lausanne). 2018 Apr 30;5:121. (PMID: 29761104)
J Thromb Haemost. 2016 Mar;14(3):438-48. (PMID: 26749406)
J Vector Borne Dis. 2018 Apr-Jun;55(2):79-88. (PMID: 30280705)

Keywords: Dengue; Haemostasis; Multiplate

0 (Biomarkers)
0 (Peptide Fragments)
0 (thrombin receptor peptide (42-47))
61D2G4IYVH (Adenosine Diphosphate)
9007-34-5 (Collagen)

Date Created: 20200809 Date Completed: 20200901 Latest Revision: 20200901

20240105

PMC7409667

10.1186/s12879-020-05248-4

32762658