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Thrombosis Journal
Published in: Thrombosis Journal 1/2020

Open Access 01-12-2020 | Vessel Injury | Research

Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice

Authors: Yanqun Xu, Yideng Liang, Leonid Parunov, Daryl Despres, Michael Eckhaus, Dorothy Scott, Mikhail Ovanesov, Evi B. Struble

Published in: Thrombosis Journal | Issue 1/2020

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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.
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Metadata
Title
Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice
Authors
Yanqun Xu
Yideng Liang
Leonid Parunov
Daryl Despres
Michael Eckhaus
Dorothy Scott
Mikhail Ovanesov
Evi B. Struble
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2020
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-020-00245-8

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