Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis

Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dread...

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Vydané v:PLoS neglected tropical diseases Ročník 11; číslo 3; s. e0005468
Hlavní autori: Birnie, Emma, Koh, Gavin C. K. W., Löwenberg, Ester C., Meijers, Joost C. M., Maude, Rapeephan R., Day, Nicholas P. J., Peacock, Sharon J., Poll, Tom van der, Wiersinga, W. Joost
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 15.03.2017
Public Library of Science (PLoS)
Predmet:
ADAMTS13 Protein - analysis
Adolescent
Adult
Aged
Antibiotics
Antigens
Biology and Life Sciences
Blood platelets
Burkholderia pseudomallei
Burkholderia pseudomallei - isolation & purification
Correlation
Cytokines
Diagnosis
Endotoxins
Female
Health aspects
Hospitals
Humans
Immunology
Infections
Infectious diseases
Inflammation
Intensive care
Male
Measurement
Medicine
Medicine and Health Sciences
Melioidosis - mortality
Melioidosis - pathology
Middle Aged
Mortality
Pathogenesis
People and Places
Pseudomonas infections
Public health
Sepsis
Stimulation
Survival Analysis
Thailand
Thrombin
Thrombocytopenia
Thrombocytopenia - pathology
Thrombosis
Tropical diseases
Vaccines
Von Willebrand factor
von Willebrand Factor - analysis
Young Adult
Southeast Asia
Netherlands
Thailand
Australia
Bangkok Thailand
ISSN:1935-2735, 1935-2727, 1935-2735
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Shrnutí:Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. We hypothesized that changes in Von Willebrand factor (VWF) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin in melioidosis, and investigated whether this impacted on outcome. We recruited 52 controls and 34 culture-confirmed melioidosis patients at Sappasithiprasong Hospital in Ubon Ratchathani, Thailand. All subjects were diabetic. Platelet counts in melioidosis patients were lower compared to controls (p = 0.0001) and correlated with mortality (p = 0.02). VWF antigen levels were higher in patients (geometric mean, 478 U/dl) compared to controls (166 U/dL, p<0.0001). The high levels of VWF in melioidosis appeared to be due to increased endothelial stimulation (VWF propeptide levels were elevated, p<0.0001) and reduced clearance (ADAMTS13 reduction, p<0.0001). However, VWF antigen levels did not correlate with platelet counts implying that thrombocytopenia in acute melioidosis has an alternative cause. Thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis. Further studies on the role of thrombocytopenia in B. pseudomallei infection are needed.
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I have read the journal's policy and the authors of this manuscript have the following competing interests: GCKWK is currently employed by GlaxoSmithKline.
Current address: Diseases of the Developing World, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom
Conceptualization: EB GCKWK NPJD SJP WJW.Data curation: EB GCKWK WJW.Formal analysis: EB GCKWK.Funding acquisition: EB GCKWK SJP WJW.Investigation: GCKWK RRM ECL JCMM.Methodology: GCKWK NPJD SJP WJW.Project administration: EB GCKWK WJW.Resources: JCMM NPJD SJP WJW.Supervision: NPJD SJP TvdP WJW.Visualization: EB GCKWK WJW.Writing – original draft: EB GCKWK WJW.Writing – review & editing: EB GCKWK JCMM TvdP WJW.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0005468