title: Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis.
abstract: 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.
authors.affiliation: Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Emma
authors.initials: E
authors.lastname: Birnie
authors.affiliation: Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.|Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kindom.|Department of Infection and Tropical Medicine, Heartlands Hospital, Birmingham, United Kindom.
authors.forename: Gavin C K W
authors.initials: GC
authors.lastname: Koh
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ester C
authors.initials: EC
authors.lastname: Löwenberg
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.|Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Rapeephan R
authors.initials: RR
authors.lastname: Maude
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|The Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kindom.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kindom.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.affiliation: Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Wiersinga
mesh_terms: D000071120:ADAMTS13 Protein / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D016957:Burkholderia pseudomallei / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016019:Survival Analysis; D013785:Thailand; D013921:Thrombocytopenia / Q000473:pathology*; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D014841:von Willebrand Factor; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human