Cardiovascular diseases generating high shear stress cause excessive cleavage of von Willebrand factor multimers, leading to acquired von Willebrand syndrome and gastrointestinal bleeding.
Acquired von Willebrand syndrome is a hemostatic disorder caused by high shear stress in various cardiovascular diseases, leading to loss of high molecular weight VWF multimers and increased bleeding risk.
The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis.VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2-80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.
Horiuchi et al. (Mon,) conducted a review in Acquired von Willebrand Syndrome associated with Cardiovascular Diseases. Cardiovascular diseases generating high shear stress cause excessive cleavage of von Willebrand factor multimers, leading to acquired von Willebrand syndrome and gastrointestinal bleeding.