Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients
Tigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason fo...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.891952/full |
| _version_ | 1818536561566810112 |
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| author | Li-Hua Sun Kun-Hao Bai Kun-Hao Bai Guo-Yan Wu Xiao-Peng Tian Zhi-Qing Zou Da-Wei Wang Yu-Jun Dai Yu-Jun Dai Si-Liang Chen |
| author_facet | Li-Hua Sun Kun-Hao Bai Kun-Hao Bai Guo-Yan Wu Xiao-Peng Tian Zhi-Qing Zou Da-Wei Wang Yu-Jun Dai Yu-Jun Dai Si-Liang Chen |
| author_sort | Li-Hua Sun |
| collection | DOAJ |
| description | Tigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is unclear. In this study, we found that tigecycline cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT), and D-dimer. In addition, through functional studies, we found that tigecycline inhibit platelet adhesion and aggregation, and the coagulation function of patients gradually recover after discontinuation. Gene sequencing results suggested that tigecycline significantly regulate the expression of genes related to platelet function pathways and increase the incidence of single nucleotide polymorphisms and the number of alternative splices in the Chinese hamster ovary (CHO) cells treated with tigecycline. An abnormal function and low numbers of platelets are common in patients with hematological malignancies. Our study can explain the mechanism of abnormal coagulation caused by tigecycline. Additionally, doctors who apply tigecycline to cure infections in tumor patients should be warned. |
| first_indexed | 2024-12-11T18:39:33Z |
| format | Article |
| id | doaj.art-163f97e5de3e4754821196246e746528 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T18:39:33Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-163f97e5de3e4754821196246e7465282022-12-22T00:54:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.891952891952Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer PatientsLi-Hua Sun0Kun-Hao Bai1Kun-Hao Bai2Guo-Yan Wu3Xiao-Peng Tian4Zhi-Qing Zou5Da-Wei Wang6Yu-Jun Dai7Yu-Jun Dai8Si-Liang Chen9Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Endoscopy, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaJiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Hematologic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaTigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is unclear. In this study, we found that tigecycline cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT), and D-dimer. In addition, through functional studies, we found that tigecycline inhibit platelet adhesion and aggregation, and the coagulation function of patients gradually recover after discontinuation. Gene sequencing results suggested that tigecycline significantly regulate the expression of genes related to platelet function pathways and increase the incidence of single nucleotide polymorphisms and the number of alternative splices in the Chinese hamster ovary (CHO) cells treated with tigecycline. An abnormal function and low numbers of platelets are common in patients with hematological malignancies. Our study can explain the mechanism of abnormal coagulation caused by tigecycline. Additionally, doctors who apply tigecycline to cure infections in tumor patients should be warned.https://www.frontiersin.org/articles/10.3389/fphar.2022.891952/fulltigecyclineabnormal coagulationcancerRNA-SeqCHO |
| spellingShingle | Li-Hua Sun Kun-Hao Bai Kun-Hao Bai Guo-Yan Wu Xiao-Peng Tian Zhi-Qing Zou Da-Wei Wang Yu-Jun Dai Yu-Jun Dai Si-Liang Chen Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients Frontiers in Pharmacology tigecycline abnormal coagulation cancer RNA-Seq CHO |
| title | Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients |
| title_full | Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients |
| title_fullStr | Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients |
| title_full_unstemmed | Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients |
| title_short | Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients |
| title_sort | mechanism of abnormal coagulation induced by tigecycline in cancer patients |
| topic | tigecycline abnormal coagulation cancer RNA-Seq CHO |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.891952/full |
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