The pathophysiology of acquired von Willebrand's Disease type 2A (vWD-2A) from an aortic stenosis (Heyde's Syndrome).a. von Willebrand Factor (vWF) passes through a normal aortic valve and remains in its coiled high molecular weigh form.b. vWF passes through a stenotic aortic valve and uncoils due to the high shear stress.c. Coiled vWF is unaffected by the catabolic enzyme ADAMTS13, and passes into regular circulation via the aorta.d. Uncoiled active vWF is cleaved in two by ADAMTS13 and becomes nonfunctional.e. In small damaged arterioles with high shear stress vWF uncoils and becomes active. It then binds to the collagen on the other side of the damaged arteriole wall. Platelets bind to vWF and release a cytokine signal that activates other clotting factors resulting in more platelet binding and the formation of a clot; bleeding stops.
f. Inactive cleaved vWF cannot bind to the collagen, and due to the high blood flow, the platelets also fail to bind (they need vWF to do so), as such a small arteriole bleed continues unabated.
Own work
Michael D. Dacre