Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice.

Abstract

BACKGROUND:

Increased plasma levels of coagulation factor (F) XI are a risk factor for venous thrombosis.

OBJECTIVE:

To further explore the relationship between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice in a ferric chloride (FeCl(3))-induced vena cava thrombosis model.

METHODS AND RESULTS:

Thrombosis was induced by 3-min topical application of filter papers containing increasing concentrations of FeCl(3) and the thrombus was measured at 30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a thrombus with 5% FeCl(3,) and were partially protected against 7.5% and 10% FeCl(3,) respectively. The protective effect was substantially stronger than a high dose of heparin (1,000 units kg(-1), i.v.), clopidogrel (30 mg kg(-1), p.o.) or argatroban (30 mg kg(-1), i.p.). These antithrombotic agents resulted in off-scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI-deficient mice was unchanged compared to wild-type mice. In addition to its known effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI-deficient mouse and human plasma compared to those supplemented with FXIa.

CONCLUSION:

Given the strong antithrombotic efficacy (possibly contributed by strong anticoagulant activity associated with increased fibrinolytic activity) and mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent venous thrombosis.

• Authors: X Wang, P L Smith, M-Y Hsu, D Gailani, W A Schumacher, M L Ogletree, D A Seiffert
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 4 Issue 9 Pg. 1982-8 (Sep 2006) ISSN: 1538-7933 [Print] England
• PMID: 16961605 (Publication Type: Journal Article)

Chemical References

• Chlorides
• Ferric Compounds
• Fibrinolytic Agents
• ferric chloride

Topics

• Animals
• Chlorides
• Disease Models, Animal
• Factor XI Deficiency (complications)
• Ferric Compounds (pharmacology)
• Fibrinolysis
• Fibrinolytic Agents (pharmacology)
• Mice
• Venae Cavae (pathology)
• Venous Thrombosis (chemically induced, prevention & control)