Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis
| Autor: | Gavin C. K. W. Koh, Tom van der Poll, Rapeephan R. Maude, Emma Birnie, Joost C. M. Meijers, W. Joost Wiersinga, Ester C. Löwenberg, Nicholas P. J. Day, Sharon J. Peacock |
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| Přispěvatelé: | AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, Vascular Medicine, Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Bacterial Diseases Melioidosis Burkholderia pseudomallei Physiology 030204 cardiovascular system & hematology Pathology and Laboratory Medicine Pathogenesis 0302 clinical medicine Endocrinology Animal Cells hemic and lymphatic diseases Medicine and Health Sciences Platelet biology lcsh:Public aspects of medicine Hematology Middle Aged Thailand ADAMTS13 3. Good health Body Fluids Infectious Diseases Blood Female Anatomy Cellular Types Research Article Adult Platelets lcsh:Arctic medicine. Tropical medicine Adolescent Endocrine Disorders Death Rates lcsh:RC955-962 ADAMTS13 Protein Blood Plasma Sepsis 03 medical and health sciences Young Adult Signs and Symptoms Von Willebrand factor Diagnostic Medicine Diabetes mellitus von Willebrand Factor medicine Diabetes Mellitus Humans Secretion Aged Demography Blood Cells business.industry Public Health Environmental and Occupational Health Correction Biology and Life Sciences lcsh:RA1-1270 Cell Biology medicine.disease biology.organism_classification Survival Analysis Thrombocytopenia 030104 developmental biology Metabolic Disorders Immunology People and Places biology.protein business Physiological Processes |
| Zdroj: | PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005468 (2017) PLoS neglected tropical diseases, 11(3):e0005468. Public Library of Science PLoS Neglected Tropical Diseases |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | 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 Author summary Melioidosis, caused by bioterror threat agent Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and Northern Australia. Recently, it has been predicted that the annual burden of melioidosis is much higher than previously thought, with 165.000 human cases from which 89.000 patients die worldwide. Melioidosis has a mortality up to 40% despite appropriate antibiotic treatment and there is currently no vaccine available. Therefore, it is of importance to better understand the pathogenesis of this debilitating disease. There is extensive cross talk between the innate immune system and blood coagulation, which contributes to the host defense against invading bacteria. One of the hallmark features of melioidosis is extensive abnormalities in the coagulation system. Therefore, we hypothesized that, since endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin all occur in melioidosis, these would result in derangements of Von Willebrand factor (a protein involved in hemostasis and platelet aggregation). In a cohort of culture-confirmed patients with severe melioidosis, we found that thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, our study showed that excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis. |
| Databáze: | OpenAIRE |
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