It has been hypothesized that GI mucosal ischemia secondary to low cardiac output that occurs with severe AVS is the leading cause of recurrent bleeding.[21,22] There is growing evidence that low-level VWF caused by high shear rate increases the vulnerability to bleeding.[20] The pathophysiology of HS is multifactorial, and the relationship between AVS and angiodysplasia remains controversial. The gene discussed is VWF; the disease is histiocytic sarcoma.