The aortic valve is the valve between the left ventricle and the aorta, the main artery. It has three leaflets (tricuspid). When the left ventricle contracts, it pushes blood through the valves and into the aorta. When the left ventricle relaxes, the valves close, preventing the blood from flowing back into the left ventricle.

When the aortic opening becomes constricted or stenotic, the blood in the left ventricle cannot be pumped effectively into the aorta. Aortic stenosis (AS) is usually age-related and is caused by progressive calcification of any of the three leaflets of the valve.

Severe aortic stenosis also causes an acquired form of von Willebrand disease (vWD type 2A). This is due to breakdown of the von Willebrand factor (vWF) by the increased turbulence around the stenotic valve. The increased turbulence causing high shear stress conditions predisposes the vWF to cleavage by an enzyme, ADAMTS-13. This enzyme is the 13^th member of the class of enzymes known as a disintegrin and metalloproteinase with a thrombospondin type 1 motif also known as von Willebrand factor-cleaving protease (vWFCP).

This acquired form of vWD causes bleeding in the AS patient. Whether the bleeding is due to platelet adhesion or to platelet aggregation has not been determined. This is the subject of the study done by Panzer, et.al. using the IMPACT-R machine. The study concludes that reduced levels of large vWF multimers associated with severe AS leads to impairment of both adhesion and aggregation of platelets. An abstract of the study can be found here.

Impact-R CPA test can be a useful screening test for von Willebrand Disease.

Von Willebrand Disease or vWD is the most common hereditary bleeding disorder. It is caused by a deficiency in the von Willebrand Factor (vWF).  VWF has two main functions in the coagulation cascade: 1) it is the major adhesion molecule that anchors the platelets to the exposed subendothelium, and 2) it is the binding protein for Factor VIII (FVIII). The clinical manifestations of vWD is due to its effect on platelet function.

Patients with vWD present mostly with mucosal bleeding and sometimes with post-operative bleeding.  Signs and symptoms include: bruising in uncommon areas of the body, prolonged epistaxis, heavy menstrual bleeding or menorrhagia, prolonged bleeding at dental extraction sites, or during tonsillectomies.

VWD has 3 major types (Type 1, 2, and 3) with Type 2 having 4 subtypes (Type 2A, 2B, 2M, and 2N). The most common is Type 1. The following table compares the Activated Partial Thromboplastin Time (aPTT), vWF antigen, vWF activity, and FVIII activity of the different types.

Von Willebrand factor replacement is the definitive therapy for vWD especially as prophylaxis for major procedures to reduce the risk of post-operative bleeding. For minor procedures and for mild Type 1 vWD treatment of choice is 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) which causes the release of vWF and FVIII from endothelial stores. It can be given intravenously or by an intranasal spray.

Diagnosis is done by careful history and physical exam with a combination of several laboratory tests such as aPTT, ristocetin cofactor assay, collagen binding activity multimer assays. A useful screening test to determine decreased platelet function is the IMPACT-R Cone and Platelet Analyzer (CPA) which tests platelet adhesion and aggregation in anti-coagulated whole blood under arterial flow conditions. This test is qualitative compared to the merely quantitative platelet count.