Vessel-blocking thrombus formation (white) in damaged mesenteric vessels is prevented in the absence of coagulation factor XII (bottom panels).
Blood clotting depends on the sequential activation of proteins, called clotting factors, that culminates in the production of fibrin—the protein that forms the meshwork of the clot. This process must be tightly regulated, as too little clotting can lead to bleeding disorders and too much clotting can lead to blood vessel blockage, which triggers strokes and heart attacks.
Deficiencies in some blood clotting proteins, such as tissue factor and factor VII, result in fatal bleeding disorders. But deficiencies in FXII are not associated with abnormal bleeding, and thus this factor has long been considered dispensable for normal clotting.
Renné and colleagues now reexamine a role for this clotting factor in FXII-deficient mice. As they had previously reported (and similar to the situation in humans), these mice developed no spontaneous bleeding disorders. However, the FXII-deficient mice were less likely to develop blocked arteries (thrombosis) in response to induced vessel injury. Thrombosis formation was initiated normally in the FXII-deficient mice, but the clots were unstable and detached from the vessel wall before they could grow large enough to impede blood flow, suggesting that FXII is required not to initiate, but rather to propagate, the clotting reaction.
Consistent with these findings, elevated plasma levels of FXII in humans have been associated with increased coronary artery disease, and lower levels with protection. Thus the authors suggest that drugs that inhibit FXII might be useful in treating heart disease without increasing the risk of spontaneous bleeding. FXII-driven fibrin formation thus appears to be essential for pathological thrombus formation. The beneficial effects of this pathway, however, remain mysterious. 
