[3] It is caused by cleavage of Von Willebrand factor (vWF) due to high shear stress forces from aortic valvular stenosis.

Platelets are attracted to this activated form of von Willebrand factor and they accumulate and block the damaged area, preventing bleeding [citation needed].

[6][7][8] As part of the normal hemostasis of the blood, when von Willebrand factor changes conformation into its active state, it is degraded by its natural catabolic enzyme ADAMTS13, rendering it incapable of binding the collagen at an injury site.

[4][7] It has been hypothesized that defects in high molecular weight von Willebrand factor could actually be the cause of the arteriovenus malformations in intestinal angiodysplasia, rather than just making existing angiodysplasic lesions bleed.

[4][11] Heyde's syndrome is now known to be gastrointestinal bleeding from angiodysplasic lesions due to acquired vWD-2A deficiency secondary to aortic stenosis, and the diagnosis is made by confirming the presence of those three things.

While Heyde's syndrome may exist alone with no other symptoms of aortic stenosis,[2] the person could also present with evidence of heart failure, fainting, or chest pain.

Desmopressin is thus sometimes used directly to treat mild to moderate acquired von Willebrand's disease and is an effective prophylactic agent for the reduction of bleeding during heart valve replacement surgery.

[23] The American internist Edward C. Heyde originally described the syndrome in a 1958 letter to the New England Journal of Medicine, reporting on ten patients with the association.

[citation needed] In the 45 years following its initial description, no plausible explanations could be found for the association between aortic valve stenosis and gastrointestinal bleeding.

[citation needed] Several hypotheses for the association were proposed, the most prominent being the idea that there is no causal relationship between aortic stenosis and gastrointestinal bleeding, they are both just common conditions in the elderly, and they sometimes overlap.

They used this fact to hypothesize that this may mean that von Willebrand factor is activated in the narrowed stenotic aortic valve and thus cleared from circulation at a much higher rate than in healthy individuals.