An inhibitory anti-factor IX antibody effectively reduces thrombus formation in a rat model of venous thrombosis.
An inhibitory anti-factor IX/IXa antibody (BC2) has been investigated as an anti-thrombotic agent in a rat venous thrombosis model. The treatment of rats post-injury with a single bolus dose of BC2 (3 mg/kg, i.v.) resulted in an approximately 4 fold reduction in venous thrombus mass (P = 0.043). This efficacy was matched by a minimal (<2.5 fold) prolongation of the aPTT and had no effect on the prothrombin time (PT). Heparin by comparison, given as a bolus followed by continuous infusion, at doses comparable in efficacy at reducing thrombus formation, prolonged the aPTT >50 fold. These results demonstrate that the anti-factor IX/IXa antibody (BC2), when compared to heparin, can effectively reduce venous thrombosis with less disruptive consequences on blood clotting.
Feuerstein
G Z
GZ
SmithKline Beecham Pharmaceuticals, Department of Cardiovascular Pharmacology, King of Prussia, PA, USA.
Toomey
J R
JR
Valocik
R
R
Koster
P
P
Patel
A
A
Blackburn
M N
MN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D004353:Drug Evaluation, Preclinical; D000939:Epitopes / Q000276:immunology; D005164:Factor IX / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D015949:Factor IXa / Q000276:immunology; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D010314:Partial Thromboplastin Time; D017434:Protein Structure, Tertiary; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D014682:Vena Cava, Inferior; D020246:Venous Thrombosis / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005164:Factor IX; D006493:Heparin; D015949:Factor IXa