Anticoagulant potential of an antibody against factor VII.
BACKGROUND
Hypercoagulability often resulting from sepsis, trauma, and other conditions is widely associated with thrombotic and cardiovascular disorders. The development of effective and safe anticoagulation is in great demand to relieve complications and improve human health.


OBJECTIVE
We study the anticoagulant potential of a polyclonal antibody to human FVII (anti-hFVII Ab).


RESULTS
Preincubating FVII with anti-hFVII Ab, we showed the significantly blocked tissue factor (TF)-dependent FVII activation monitored by a two-stage chromogenic assay. Consistently, the antibody depressed TF/FVII-catalyzed FX activation was shown on Western blotting analysis. As a result, TF procoagulation derived from rabbit brain thromboplastin was prolonged significantly by the preincubation of human normal plasma with the antibody, which mimicked FVII-deficient plasma in a single-stage clotting assay. In contrast, the anti-hFVII Ab had no effect on either FVIIa amidolytic activity or TF/FVIIa binary complex.


CONCLUSIONS
Anti-hFVII Ab readily blocked clot formation, which was mediated by the upstream downregulation of the extrinsic coagulation of inhibiting FVII activation. Further research warrants establishing its in vivo application as an anticoagulant.
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology*; D000925:Anticoagulants / Q000097:blood / Q000276:immunology* / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects* / Q000276:immunology; D005167:Factor VII / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D011817:Rabbits; D012756:Sheep; D013925:Thromboplastin / Q000276:immunology
D000906:Antibodies; D000925:Anticoagulants; D005167:Factor VII; D013925:Thromboplastin