New approach prevents thrombosis without increasing the risk of bleeding; an antibody, 3F7, blocks Factor XII
Researchers at Karolinska Institutet in Sweden, in collaboration with an international team, have developed an antibody, 3F7, which blocks a protein that is active in the coagulation system factor XII.
Inhibition of factor XII makes it possible to prevent thrombosis in blood vessels without increasing the risk of bleeding in clinical settings.
Thrombosis is caused by blood clotting; clots can block blood flow in one or more blood vessels and so cause thrombotic diseases such as stroke, myocardial infarction or pulmonary embolism.
Currently, the thrombosis is prevented or treated by means of anticoagulants. There is a broad variety of anticoagulant drugs, such as Warfarin ( a vitamin K inhibitor; Coumadin ), the novel oral anticoagulants ( Apixaban [ Eliquis ], Dabigatran [ Pradaxa ] or Rivaroxaban [ Xarelto ] ) and drugs of the Heparin group. All of these agents target different components of the blood coagulation system to prevent blood from clotting and thus to interfere with thrombosis. However, all these drugs also entail an increased risk of bleeding in patients that partially offsets their beneficial effects.
The blocking of coagulation factor XII ( FXII ) functions differently compared to traditional anticoagulants. It has been known for long time that humans that are deficient in FXII do not bleed excessively and because of that FXII was believed to have no function for blood coagulation in patients.
In 2005, Thomas Renné and his research team discovered that mice lacking FXII could have neither a stroke nor pulmonary embolism, even though they had normal bleeding patterns.
The researchers developed and tested the antibody, called 3F7, in rabbits during an ECMO treatment. ECMO is an advanced heart-lung machine used in life-threatening conditions especially in infants. Contact with the plastic tubing causes the blood to clot, so patients are routinely administered with anticoagulants ( Heparin ). However due to the Heparin anticoagulation patients bleed excessively and a substantial number even dies from these bleedings.
In the study, thrombosis in rabbits on ECMO receiving 3F7 decreased was as low as rabbits receiving heparin, but the risk of bleeding with 3F7 was minimal, whereas Heparin-treatment led to bleeding.
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. ( Xagena )
Source: Karolinska Institutet, 2014