Beyond Acquired Von Willebrand Deficiency: Exploring Alternative Mechanisms of Heyde's Syndrome

Heyde's syndrome (HS) is a complex condition characterized by the coexistence of severe aortic stenosis (AS) and gastrointestinal (GI) angiodysplasia. The prevailing belief has been that acquired von-Willebrand factor deficiency (AVWD) is the underlying cause of HS. However, the validity of this theory remains contentious, as there have been reports of bleeding angiodysplasia in the setting of AS despite normal von-Willebrand factor (vWF) activity. Here, we present a compelling case of HS with negative diagnostic testing for AVWD. A 61-year-old female with a history of end-stage renal disease on hemodialysis, AS, and a history of recurrent GI bleeding presented with dyspnea. Prior to arrival, she reported multiple episodes of melena and hematochezia and was found to have a hemoglobin of 6 g/dL. Notable exam findings included melenic stool on digital rectal exam and a grade three systolic crescendo-decrescendo murmur that radiated up to the carotids. A transthoracic echocardiogram demonstrated evidence of severe AS. Considering the recurrent GI bleeding and severe AS, HS was suspected. To investigate this further, a vWF disease panel was sent, revealing a normal multimeric pattern. Given hemodynamic stability, she was discharged but had multiple readmissions soon after with recurrent GI bleeding requiring endoscopic intervention. On her last visit, she underwent transcatheter aortic valve replacement (TAVR) with notable resolution in her GI bleeds thereafter. The prevailing theory regarding the etiology of HS is acquired vWF deficiency. However, the validity of this theory remains a topic of debate, as a growing body of evidence suggests that the absence of AVWD does not necessarily rule out the diagnosis. The absence of AVWD in our patient raises questions about its prevalence in HS and its status as a key feature and highlights the importance of considering HS events without AVWD, given the risk of recurrent life-threatening GI bleeds.