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


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.


CONCLUSIONS
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.
Wang
X
X
Department of Thrombosis Research, Bristol-Myers Squibb Company, Pennington, NJ 08534, USA. wangxk2000@yahoo.com
Smith
P L
PL
Hsu
M-Y
MY
Gailani
D
D
Schumacher
W A
WA
Ogletree
M L
ML
Seiffert
D A
DA
D000818:Animals; D002712:Chlorides; D004195:Disease Models, Animal; D005173:Factor XI Deficiency / Q000150:complications*; D005290:Ferric Compounds / Q000494:pharmacology*; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000494:pharmacology; D051379:Mice; D014684:Venae Cavae / Q000473:pathology*; D020246:Venous Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
D002712:Chlorides; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; C024555:ferric chloride