Related Experiment Video
Updated: Jul 22, 2026
Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel
Published on: June 29, 2015
Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice
1Department of Thrombosis Research, Bristol-Myers Squibb Company, Pennington, NJ 08534, USA. xinkand.wang@bms.com
Abstract:
Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases required for normal hemostasis. The purpose of this work was to evaluate FXI and FIX as potential therapeutic targets by means of a refined ferric chloride (FeCl(3))-induced arterial injury model in factor-deficient mice. Various concentrations of FeCl(3) were used to establish the arterial thrombosis model in C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient mice were fully protected from occlusion induced by 5% FeCl(3), and were partially protected against the effect of 7.5% FeCl(3). The protective effect was comparable to very high doses of heparin (1000 units kg(-1)) and substantially more effective than aspirin. While FXI and FIX deficiencies were indistinguishable in the carotid artery injury model, there was a marked difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have similar bleeding times, while FIX deficiency was associated with severely prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable strategy for treating or preventing thrombus formation.
Insights
Targeting Factor XI (FXI) or Factor IX (FIX) protects against arterial thrombosis in mice. FXI deficiency offers protection without significantly increasing bleeding risk, suggesting FXI as a viable therapeutic target.
Area of Science:
- * Hemostasis and Thrombosis Research
- * Vascular Biology
- * Pharmacological Targeting of Coagulation Factors
Background:
- * Factor XI (FXI) and Factor IX (FIX) are crucial serine proteases in hemostasis.
- * Understanding their roles is key to developing new antithrombotic therapies.
- * Assessing FXI and FIX as therapeutic targets requires robust preclinical models.
Purpose of the Study:
- * To evaluate the therapeutic potential of targeting FXI and FIX.
- * To assess their roles in arterial thrombosis using a ferric chloride (FeCl3) injury model.
- * To compare the efficacy of FXI and FIX inhibition with existing anticoagulants like heparin and aspirin.
Main Methods:
- * Development of a ferric chloride (FeCl3)-induced arterial thrombosis model in C57BL/6 mice.
- * Utilized factor XI (FXI)- and factor IX (FIX)-deficient mice to assess protection against thrombosis.
- * Compared protective effects with high-dose heparin and aspirin treatments.
- * Evaluated bleeding risk using a tail-bleeding-time assay.
Main Results:
- * FeCl3 induced rapid carotid artery occlusion in wild-type mice.
- * FXI- and FIX-deficient mice showed significant protection against FeCl3-induced thrombosis.
- * FXI and FIX deficiencies conferred protection comparable to high-dose heparin and superior to aspirin.
- * FXI deficiency showed minimal impact on bleeding time, unlike FIX deficiency which caused severe bleeding.
Conclusions:
- * Both FXI and FIX are critical for arterial thrombosis formation.
- * Therapeutic inhibition of FXI presents a promising strategy for antithrombotic therapy.
- * FXI inhibition may offer a favorable risk-benefit profile due to a milder bleeding diathesis compared to FIX inhibition.
