Birnie Emma, Koh Gavin C K W, Löwenberg Ester C, Meijers Joost C M, Maude Rapeephan R, Day Nicholas P J, Peacock Sharon J, van der Poll Tom, Wiersinga W Joost
Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS Negl Trop Dis. 2017 Mar 15;11(3):e0005468. doi: 10.1371/journal.pntd.0005468. eCollection 2017 Mar.
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.
METHODS/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
类鼻疽病由生物恐怖治疗剂类鼻疽伯克霍尔德菌引起，是东南亚和澳大利亚北部社区获得性革兰氏阴性败血症的重要病因。对类鼻疽病发病机制的新见解可能有助于改善治疗并降低这种可怕疾病的死亡率。基于类鼻疽病中内毒素、促炎细胞因子和凝血酶对内皮细胞的刺激，我们推测类鼻疽病中血管性血友病因子（VWF）功能会发生变化，并研究了这是否会影响预后。
方法/主要发现：我们在泰国乌汶叻差他尼的萨帕西提普拉松医院招募了52名对照者和34名经培养确诊的类鼻疽病患者。所有受试者均患有糖尿病。类鼻疽病患者的血小板计数低于对照组（p = 0.0001），且与死亡率相关（p = 0.02）。患者的VWF抗原水平（几何平均值为478 U/dl）高于对照组（166 U/dL，p<0.0001）。类鼻疽病中VWF水平升高似乎是由于内皮细胞刺激增加（VWF前肽水平升高，p<0.0001）和清除减少（ADAMTS13减少，p<0.0001）。然而，VWF抗原水平与血小板计数不相关，这意味着急性类鼻疽病中的血小板减少有其他原因。
结论/意义：血小板减少是类鼻疽病的关键特征，且与死亡率相关。此外，VWF过量和ADAMTS13缺乏是急性类鼻疽病的特征，但不是类鼻疽病中血小板减少的主要驱动因素。需要进一步研究血小板减少在类鼻疽伯克霍尔德菌感染中的作用。
