The XII factor

Factor XII sits atop one branch of the clotting cascade but has not been pursued for treating and preventing thrombosis because it was seen as a minor player in blood coagulation. Now, a group from the Karolinska Institute and CSL Ltd. has shown that inhibiting the factor can prevent clotting without increasing the risk of bleeding,1 making it one of the only anticoagulants able to accomplish such a feat.

A group from Isis Pharmaceuticals Inc. and McMaster University obtained similar results with factor XII,2 but the biotech maintains that blocking a downstream target, factor XI, is a better approach.

Whether blocking factor XII or factor XI will be a better strategy will probably be determined in the clinic (see "Targeting the intrinsic pathway of coagulation and the kallikrein-kinin system").

Passing over factors

The main reason factor XII was passed over as an anticoagulant stemmed from observational studies of patients who had a deficiency of the enzyme. Those patients had normal hemostatic capacity-the formation of fibrin-based clots-and did not have an increased risk of bleeding from either an injury or a spontaneous event.3

As a result, said Thomas Renné, almost everyone assumed that factor XII was not important for forming clots. Renné, a professor of clinical chemistry and coagulation research at the Karolinska Institute and

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