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.
For decades, scientists assumed that factor XII (or Hageman factor) was not important for clotting, as both humans and mice that lack this protein do not develop bleeding disorders. Bernhard Nieswandt and his colleagues now show that mice that lack factor XII did not develop blocked arteries in response to blood vessel injury. Although clot formation was initiated at the sight of injury in the factor XII-deficient mice, the clots detached from the blood vessel wall before they could grow large enough to impede blood flow.
Consistent with these findings, studies in humans have shown that elevated levels of factor XII in the blood have been associated with increased coronary artery disease and lower levels with protection. Nieswandt thus suggests that drugs that inhibit this protein might be useful for treating certain types of heart disease without the increased risk of spontaneous bleeding that accompanies traditional blood-thinning drugs.
Journal
Journal of Experimental Medicine