Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice
Abstract Background Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been assoc...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12959-020-00245-8 |
| _version_ | 1818550837435170816 |
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| author | Yanqun Xu Yideng Liang Leonid Parunov Daryl Despres Michael Eckhaus Dorothy Scott Mikhail Ovanesov Evi B. Struble |
| author_facet | Yanqun Xu Yideng Liang Leonid Parunov Daryl Despres Michael Eckhaus Dorothy Scott Mikhail Ovanesov Evi B. Struble |
| author_sort | Yanqun Xu |
| collection | DOAJ |
| description | Abstract Background Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown. Methods Late pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20 min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro. Results FXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3 injury, pregnant and non-pregnant mice receiving IG + FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody. Conclusions Our results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals. |
| first_indexed | 2024-12-12T08:51:50Z |
| format | Article |
| id | doaj.art-54e8e2e2d34546058d8303ab1176206b |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-12-12T08:51:50Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-54e8e2e2d34546058d8303ab1176206b2022-12-22T00:30:11ZengBMCThrombosis Journal1477-95602020-11-0118111010.1186/s12959-020-00245-8Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in miceYanqun Xu0Yideng Liang1Leonid Parunov2Daryl Despres3Michael Eckhaus4Dorothy Scott5Mikhail Ovanesov6Evi B. Struble7Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationMouse Imaging Facility, National Institutes of HealthPathology Service, Division of Veterinary Resources, National Institutes of HealthCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research, U.S. Food and Drug AdministrationAbstract Background Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown. Methods Late pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20 min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro. Results FXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3 injury, pregnant and non-pregnant mice receiving IG + FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody. Conclusions Our results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals.http://link.springer.com/article/10.1186/s12959-020-00245-8Factor XIaFXIaThrombogenicityImmune globulinThrombosis |
| spellingShingle | Yanqun Xu Yideng Liang Leonid Parunov Daryl Despres Michael Eckhaus Dorothy Scott Mikhail Ovanesov Evi B. Struble Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice Thrombosis Journal Factor XIa FXIa Thrombogenicity Immune globulin Thrombosis |
| title | Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice |
| title_full | Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice |
| title_fullStr | Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice |
| title_full_unstemmed | Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice |
| title_short | Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice |
| title_sort | combined thrombogenic effects of vessel injury pregnancy and procoagulant immune globulin administration in mice |
| topic | Factor XIa FXIa Thrombogenicity Immune globulin Thrombosis |
| url | http://link.springer.com/article/10.1186/s12959-020-00245-8 |
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