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Published on: August 14, 2017
Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis
Emma Birnie1, Gavin C K W Koh1,2,3,4, Ester C Löwenberg5
1Center for Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Background:
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.
Insights
Melioidosis causes low platelet counts linked to mortality. While excess Von Willebrand factor (VWF) and ADAMTS13 deficiency occur, they don't drive this thrombocytopenia, requiring further research into Burkholderia pseudomallei infection.
Area of Science:
- Infectious Diseases
- Hematology
- Pathogenesis of bacterial infections
Background:
- Melioidosis, a severe Gram-negative sepsis caused by Burkholderia pseudomallei, is prevalent in Southeast Asia and Northern Australia.
- Understanding melioidosis pathogenesis is crucial for improving treatment and reducing mortality.
- The study investigated potential changes in Von Willebrand factor (VWF) function due to endothelial stimulation and thrombin presence in melioidosis.
Purpose of the Study:
- To investigate the role of Von Willebrand factor (VWF) and ADAMTS13 in melioidosis.
- To determine the relationship between VWF, platelet counts, and mortality in melioidosis patients.
- To explore the underlying causes of thrombocytopenia in acute melioidosis.
Main Methods:
- Recruited 34 culture-confirmed melioidosis patients and 52 diabetic controls in Thailand.
- Measured platelet counts, VWF antigen, VWF propeptide, and ADAMTS13 levels.
- Analyzed correlations between these parameters and patient mortality.
Main Results:
- Melioidosis patients exhibited significantly lower platelet counts compared to controls, correlating with mortality.
- Elevated VWF antigen levels were observed in patients, attributed to increased endothelial stimulation and reduced VWF clearance (ADAMTS13 deficiency).
- VWF levels did not correlate with platelet counts, suggesting alternative causes for thrombocytopenia.
Conclusions:
- Thrombocytopenia is a significant feature of melioidosis, associated with increased mortality.
- Excess VWF and ADAMTS13 deficiency are present in acute melioidosis but do not primarily cause thrombocytopenia.
- Further research is needed to elucidate the mechanisms of thrombocytopenia in Burkholderia pseudomallei infections.
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