oxygenator membranes
Credit: Kjell Hultenby
A newly developed antibody can prevent thrombosis without increasing the risk of bleeding in rabbits, according to research published in Science Translational Medicine.
The antibody, called 3F7, works by blocking a protein that’s active in the coagulation system factor XII (FXII).
Scientists have long known that humans deficient in FXII do not bleed excessively.
And in 2005, Thomas Renné, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, and his colleagues discovered that mice lacking FXII could have neither a stroke nor a pulmonary embolism, even though they had normal bleeding patterns.
“Since then, our goal has been to find an effective way to block FXII,” Dr Renné said. “Now, we have developed an antibody that blocks FXII in human blood, mice, and rabbits. This provides protection against thrombosis without increasing the risk of bleeding.”
The researchers tested 3F7 in rabbits during extracorporeal membrane oxygenation (ECMO) treatment. ECMO is an advanced heart-lung machine used in life-threatening conditions, but contact with the plastic tubing causes the blood to clot.
The incidence of thrombosis in rabbits on ECMO receiving 3F7 was as low as in rabbits receiving heparin. There were significantly fewer fibrin clots in the oxygenators of 3F7-treated rabbits and heparin-treated rabbits than in saline-treated controls—4 ± 3%, 8 ± 6%, and 100 ± 19%, respectively.
However, bleeding was more severe in the heparin-treated rabbits than in 3F7-treated rabbits and controls. Incision-provoked skin bleeding time was more than 600 seconds in the heparin group, 160 ± 40 s in the 3F7 group, and 130 ± 15 s in controls.
Cuticle bleeding time was more than 600 s in the heparin group, 165 ± 40 s in the 3F7 group, and 120 ± 30 s in controls. The mean blood loss from cuticle wounds was 5.1 ± 1.1 mL/10 min, 0.3 ± 0.1 mL/10 min, and 0.2 ± 0.05 mL/10 min, respectively.
“Blocking FXII appears to be an effective strategy against thrombus formation, and we have shown this in experiments on rabbits in a clinically relevant context,” Dr Renné said in conclusion.
“We plan to test the antibody in a phase 1 study. It is possible that the antibody also blocks inflammation mediated by FXII, an interesting area for future studies.”
