Factor XIII Prevents Pulmonary Emboli in Mice by Stabilizing Deep Vein Thrombi.

Authors:
Shana A Shaya
Shana A Shaya
Thrombosis and Atherosclerosis Research Institute
Dhulfiha Muzafar Gani
Dhulfiha Muzafar Gani
Thrombosis and Atherosclerosis Research Institute
Jeffrey I Weitz
Jeffrey I Weitz
McMaster University
Canada
Paul Y Kim
Paul Y Kim
Queen's University
Canada
Peter L Gross
Peter L Gross
McMaster University
Canada

Thromb Haemost 2019 Apr 20. Epub 2019 Apr 20.

Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.

Background:  Deep vein thrombosis (DVT) can lead to pulmonary embolism (PE), but the mechanisms responsible for this progression are unknown. Previously, we showed that inhibition of thrombin-mediated activation of factor (F) XIII promotes venous thrombus stability in a murine model.

Aim:  In this study, we investigate the consequence of attenuating fibrinolysis, using FXIII, α-antiplasmin (α-AP) or ε-aminocaproic acid (EACA) supplementation, on clot lysis and venous thrombus stability using the same mouse model.

Methods:  In vitro plasma clot lysis assay shows that EACA and α-AP but not FXIII, inhibit fibrinolysis. Ferric chloride induced thrombi in the femoral vein of mice. After thrombus formation, mice received saline, EACA, α-AP or FXIII, with or without dalteparin or dabigatran. Thrombus sizes and embolization over 2 hours were visualized using intravital videomicroscopy. Lungs were sectioned to quantify emboli presence via histology.

Results:  The change in thrombus size over time was significantly greater after EACA treatment, but not FXIII or α-AP supplementation, compared with saline. α-AP-supplementation did not alter thrombus stability. Thrombi were more stable following EACA treatment and FXIII supplementation as evidenced by less embolic events and PE burden, even when they were anticoagulated with either dalteparin or dabigatran.

Conclusion:  FXIII supplementation stabilized venous thrombi, even in the presence of anticoagulants, and did not alter thrombus size. Supplemental FXIII may be useful to stabilize DVT and be an alternative adjunctive treatment to minimize PE, even when anticoagulants are used.

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Source
http://dx.doi.org/10.1055/s-0039-1685141DOI Listing
April 2019
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