Aortic stenosis is associated with which of the following coagulation disorders?
A. von Willebrands disease (vWD)
B. Factor VII deficiency
C. Protein C deficiency
D. Factor V deficiency
E. Factor IV deficiency
F. Factor VI deficiency
The answer is A.
Ok, whose mind is blown? First, the wrong answers. AS is not associated with Factor V, VII or protein C deficiency. Factor IV is calcium and Factor VI really doesn't exist as it was first named (probably factor Va). So, what about vWF? Aortic-valve stenosis can be complicated by bleeding, particularly that due to gastrointestinal angiodysplasia (Heyde's syndrome). I know, another syndrome name. This hemorrhagic syndrome is associated with acquired type 2A von Willebrand syndrome, which is characterized by the loss of the largest multimers of von Willebrand factor. Proteolysis of von Willebrand factor as it passes through the stenotic valve is one of the proposed causes of the bleeding. High shear forces can induce structural changes in the shape of the von Willebrand factor molecule, leading to exposure of the bond between amino acids 842 and 843, which is sensitive to the action of a specific von Willebrand protease. This results in proteolysis of the highest molecular-weight multimers of von Willebrand factor, which are the most effective in platelet mediated hemostasis under conditions of high shear stress. Essentially, the large multimers are deactivated because of this shear stress as these proteins cross through a stenotic valve. This concept is further supported by the recent demonstration that the biologic abnormalities can be corrected by valve replacement. A NEJM article[1] speaks to how common this actually is and even suggests it as a criteria (as a symptom) for valve replacement. Who knew? Crazy, right.