Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial
Abstract Background Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. Methods First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the...
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BMC
2017-05-01
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Series: | Journal of Hematology & Oncology |
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Online Access: | http://link.springer.com/article/10.1186/s13045-017-0476-1 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mei-feng Li Xiao-li Li Kai-liang Fan Ying-yi Yu Jing Gong Shu-ying Geng Ya-feng Liang Ling Huang Ji-hua Qiu Xing-han Tian Wen-ting Wang Xiao-lu Zhang Qing-xia Yu Yuan-feng Zhang Peng Lin Li-na Wang Xin Li Ming Hou Lu-yi Liu Jun Peng |
spellingShingle |
Mei-feng Li Xiao-li Li Kai-liang Fan Ying-yi Yu Jing Gong Shu-ying Geng Ya-feng Liang Ling Huang Ji-hua Qiu Xing-han Tian Wen-ting Wang Xiao-lu Zhang Qing-xia Yu Yuan-feng Zhang Peng Lin Li-na Wang Xin Li Ming Hou Lu-yi Liu Jun Peng Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial Journal of Hematology & Oncology Sepsis Thrombocytopenia Oseltamivir Desialylation Platelet |
author_facet |
Mei-feng Li Xiao-li Li Kai-liang Fan Ying-yi Yu Jing Gong Shu-ying Geng Ya-feng Liang Ling Huang Ji-hua Qiu Xing-han Tian Wen-ting Wang Xiao-lu Zhang Qing-xia Yu Yuan-feng Zhang Peng Lin Li-na Wang Xin Li Ming Hou Lu-yi Liu Jun Peng |
author_sort |
Mei-feng Li |
title |
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
title_short |
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
title_full |
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
title_fullStr |
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
title_full_unstemmed |
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
title_sort |
platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial |
publisher |
BMC |
series |
Journal of Hematology & Oncology |
issn |
1756-8722 |
publishDate |
2017-05-01 |
description |
Abstract Background Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. Methods First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. Results The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. Conclusions Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. Trial registration Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 . |
topic |
Sepsis Thrombocytopenia Oseltamivir Desialylation Platelet |
url |
http://link.springer.com/article/10.1186/s13045-017-0476-1 |
work_keys_str_mv |
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doaj-ad3f668e196d40f597edc62e25e3d9fa2020-11-24T21:48:17ZengBMCJournal of Hematology & Oncology1756-87222017-05-0110111010.1186/s13045-017-0476-1Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trialMei-feng Li0Xiao-li Li1Kai-liang Fan2Ying-yi Yu3Jing Gong4Shu-ying Geng5Ya-feng Liang6Ling Huang7Ji-hua Qiu8Xing-han Tian9Wen-ting Wang10Xiao-lu Zhang11Qing-xia Yu12Yuan-feng Zhang13Peng Lin14Li-na Wang15Xin Li16Ming Hou17Lu-yi Liu18Jun Peng19Department of Hematology, Qilu Hospital, Shandong UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityDepartment of Hematology, Qilu Hospital, Shandong UniversityDepartment of Hematology, Qilu Hospital, Shandong UniversityDivision of Preventive Medicine, Center for Disease Control and Prevention of Yantai Development ZoneDepartment of Internal Medicine, Infectious Disease Hospital of YantaiIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, Yantaishan Hospital of YantaiDepartment of Hematology, Qilu Hospital, Shandong UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityDepartment of Internal Medicine, Infectious Disease Hospital of YantaiDepartment of Hematology, Qilu Hospital, Shandong UniversityDepartment of Hematology, Qilu Hospital, Shandong UniversityIntensive Care Unit, and Clinical Laboratory, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityDepartment of Hematology, Qilu Hospital, Shandong UniversityAbstract Background Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. Methods First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. Results The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. Conclusions Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. Trial registration Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .http://link.springer.com/article/10.1186/s13045-017-0476-1SepsisThrombocytopeniaOseltamivirDesialylationPlatelet |