Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice
Abstract Introduction Hypercoagulability contributes to the majority of deaths and organ failure associated with obstructive jaundice (OJ). However, the exact mechanism of the coagulopathy in OJ remains elusive. Our objectives were to demonstrate whether phosphatidylserine (PS) exposure on blood cel...
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BMC
2025-03-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-025-03739-9 |
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| author | Muxin Yu Chuwei Zheng Xiaoguang Wang Rong Peng Guoming Lu Jinming Zhang |
| author_facet | Muxin Yu Chuwei Zheng Xiaoguang Wang Rong Peng Guoming Lu Jinming Zhang |
| author_sort | Muxin Yu |
| collection | DOAJ |
| description | Abstract Introduction Hypercoagulability contributes to the majority of deaths and organ failure associated with obstructive jaundice (OJ). However, the exact mechanism of the coagulopathy in OJ remains elusive. Our objectives were to demonstrate whether phosphatidylserine (PS) exposure on blood cells (BCs), microparticles (MPs), and endothelial cells (ECs) can account for the hypercoagulability and liver damage in OJ patients. Methods We evaluated OJ patients at two time point, which before (Day 0) and 7 days (Day 7) after the endoscopic retrograde cholangiopancreatography procedure (ERCP), and compared with healthy controls. Lactadherin was used to quantify PS exposure on BCs, MPs and ECs. Human umbilical vein endothelial cells (HUVECs) were incubated with serum of OJ patients and the expression of PS were evaluated. Meanwhile, healthy BCs and HUVECs were treated with 0, 25, 50 or 100µM unconjugated bilirubin (UCB) and PS exposure on cells were evaluated. Procoagulant activity was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. In addition, we established a cholestatic mouse model by bile duct ligation to determine the potential role of PS in intrahepatic coagulation and liver damage. Results Using flow cytometry, we found that OJ patients exhibited elevated levels of PS + BCs and associated MPs compared to the controls. Furthermore, the number of PS + BCs and MPs in patients at Day 0 were significantly higher than in patients at Day 7. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients at Day 0 versus serum from patients at Day 7. In vitro assays, PS exposure on BCs and HUVECs progressively increased with the concentration of UCB. Moreover, PS + BCs and MPs contributed to greatly shortened coagulation time and markedly enhanced coagulation factor Xa, thrombin, and fibrin generation. This procoagulant activity could be blocked approximately 80%, by the addition of lactadherin. Moreover, cholestatic mice exhibited significantly increased levels of liver tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. The enhanced intrahepatic coagulation and liver injury could be reversed by inhibiting PS with lactadherin. Conclusions These results highlight the pathogenic activity of PS + cells and MPs in promoting a prothrombotic environment and liver damage in OJ. As such, lactadherin, a PS blockade, may be a viable therapeutic strategy for treating such patients. |
| format | Article |
| id | doaj-art-17fb466b81aa4d29a58c2dfa002aaf17 |
| institution | OA Journals |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | BMC Gastroenterology |
| spelling | doaj-art-17fb466b81aa4d29a58c2dfa002aaf172025-08-20T01:57:47ZengBMCBMC Gastroenterology1471-230X2025-03-0125111510.1186/s12876-025-03739-9Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundiceMuxin Yu0Chuwei Zheng1Xiaoguang Wang2Rong Peng3Guoming Lu4Jinming Zhang5Department of Medicine, Jiaxing UniversityDepartment of Gastroenterology, The Second Affiliated Hospital of Jiaxing UniversityDepartment of Hepatic Surgery, The Second Affiliated Hospital of Jiaxing UniversityDepartment of Medicine, Jiaxing UniversityDepartment of Medicine, Jiaxing UniversityDepartment of Gastroenterology, The Second Affiliated Hospital of Jiaxing UniversityAbstract Introduction Hypercoagulability contributes to the majority of deaths and organ failure associated with obstructive jaundice (OJ). However, the exact mechanism of the coagulopathy in OJ remains elusive. Our objectives were to demonstrate whether phosphatidylserine (PS) exposure on blood cells (BCs), microparticles (MPs), and endothelial cells (ECs) can account for the hypercoagulability and liver damage in OJ patients. Methods We evaluated OJ patients at two time point, which before (Day 0) and 7 days (Day 7) after the endoscopic retrograde cholangiopancreatography procedure (ERCP), and compared with healthy controls. Lactadherin was used to quantify PS exposure on BCs, MPs and ECs. Human umbilical vein endothelial cells (HUVECs) were incubated with serum of OJ patients and the expression of PS were evaluated. Meanwhile, healthy BCs and HUVECs were treated with 0, 25, 50 or 100µM unconjugated bilirubin (UCB) and PS exposure on cells were evaluated. Procoagulant activity was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. In addition, we established a cholestatic mouse model by bile duct ligation to determine the potential role of PS in intrahepatic coagulation and liver damage. Results Using flow cytometry, we found that OJ patients exhibited elevated levels of PS + BCs and associated MPs compared to the controls. Furthermore, the number of PS + BCs and MPs in patients at Day 0 were significantly higher than in patients at Day 7. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients at Day 0 versus serum from patients at Day 7. In vitro assays, PS exposure on BCs and HUVECs progressively increased with the concentration of UCB. Moreover, PS + BCs and MPs contributed to greatly shortened coagulation time and markedly enhanced coagulation factor Xa, thrombin, and fibrin generation. This procoagulant activity could be blocked approximately 80%, by the addition of lactadherin. Moreover, cholestatic mice exhibited significantly increased levels of liver tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. The enhanced intrahepatic coagulation and liver injury could be reversed by inhibiting PS with lactadherin. Conclusions These results highlight the pathogenic activity of PS + cells and MPs in promoting a prothrombotic environment and liver damage in OJ. As such, lactadherin, a PS blockade, may be a viable therapeutic strategy for treating such patients.https://doi.org/10.1186/s12876-025-03739-9PhosphatidylserineMicroparticleEndothelial dysfunctionHypercoagulable stateLactadherin |
| spellingShingle | Muxin Yu Chuwei Zheng Xiaoguang Wang Rong Peng Guoming Lu Jinming Zhang Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice BMC Gastroenterology Phosphatidylserine Microparticle Endothelial dysfunction Hypercoagulable state Lactadherin |
| title | Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| title_full | Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| title_fullStr | Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| title_full_unstemmed | Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| title_short | Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| title_sort | phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice |
| topic | Phosphatidylserine Microparticle Endothelial dysfunction Hypercoagulable state Lactadherin |
| url | https://doi.org/10.1186/s12876-025-03739-9 |
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