A 79-year-old woman presents to her primary care physician because of progressive fatigue and decreased exercise tolerance over the past 6 months. She also reports several episodes of dark, tarry stools during the past year. Colonoscopy performed 8 months ago demonstrated multiple colonic angiodysplasias, which were treated endoscopically. Her medical history is significant for hypertension, hyperlipidemia, and chronic kidney disease. Current medications include atorvastatin and amlodipine. Temperature is 36.9°C (98.4°F), blood pressure is 138/78 mm Hg, pulse is 76/min, and respiratory rate is 14/min. Physical examination reveals conjunctival pallor. Cardiac auscultation demonstrates a harsh crescendo-decrescendo systolic murmur at the right upper sternal border that radiates to the carotid arteries. Carotid pulses are delayed and diminished bilaterally.
Laboratory studies show the following:
Transthoracic echocardiography demonstrates:
Which of the following is the most likely explanation for this patient’s recurrent gastrointestinal bleeding?
The correct answer is:
A) Acquired deficiency of high-molecular-weight von Willebrand factor multimers
This patient has Heyde syndrome, a classic association between severe aortic stenosis and gastrointestinal bleeding from angiodysplasia. The underlying mechanism involves acquired von Willebrand disease. As blood passes through a severely stenotic aortic valve, high shear stress causes unfolding of von Willebrand factor (vWF) multimers. These exposed multimers become susceptible to proteolysis by ADAMTS13, resulting in depletion of the high-molecular-weight multimers that are most effective at mediating platelet adhesion.
The resulting acquired von Willebrand disease predisposes patients to mucosal bleeding, particularly from fragile vascular lesions such as colonic angiodysplasias. Patients often present with recurrent iron-deficiency anemia, occult gastrointestinal bleeding, or overt melena.
A high-yield Step 2 concept is that correction of the aortic stenosis frequently resolves the bleeding tendency because the abnormal shear forces are eliminated.
Answer choice B: Autoimmune destruction of platelets, is incorrect.
Immune thrombocytopenia causes isolated thrombocytopenia due to antibody-mediated platelet destruction. This patient has a normal platelet count and a classic association between severe aortic stenosis and angiodysplasia-related bleeding.
Answer choice C: Chronic disseminated intravascular coagulation due to turbulent flow, is incorrect.
Although severe valvular disease can produce mechanical stress on blood elements, aortic stenosis does not typically cause chronic DIC. DIC would be associated with thrombocytopenia and abnormalities in coagulation studies.
Answer choice D: Deficiency of coagulation factor VIII, is incorrect.
Factor VIII deficiency causes hemophilia A, which usually presents earlier in life with hemarthroses, soft tissue bleeding, and prolonged PTT. This patient’s presentation is much more consistent with acquired von Willebrand disease.
Answer choice E: Portal hypertension causing colonic varices, is incorrect.
Portal hypertension can cause gastrointestinal bleeding but is usually associated with cirrhosis, splenomegaly, thrombocytopenia, ascites, or esophageal varices. None of these findings are present.
Key Learning Point
Heyde syndrome is the association between severe aortic stenosis, acquired von Willebrand disease, and gastrointestinal bleeding from angiodysplasia. High shear stress across the stenotic valve causes destruction of high-molecular-weight vWF multimers, impairing platelet adhesion and promoting recurrent bleeding.
