What is the mechanism by which Heyde's syndrome causes anemia?

Mechanism of Anemia in Heyde's Syndrome

Heyde's syndrome causes anemia through two distinct mechanisms: gastrointestinal bleeding from angiodysplasias and an acquired coagulopathy due to loss of high-molecular-weight von Willebrand factor multimers, both driven by the hemodynamic stress of aortic stenosis. 1, 2

Primary Pathophysiologic Mechanisms

Acquired von Willebrand Syndrome

• High shear stress from aortic stenosis stretches von Willebrand factor (vWF) molecules, making them susceptible to cleavage by vWF-cleaving protease (ADAMTS13), resulting in selective loss of high-molecular-weight multimers 1
• This creates an acquired von Willebrand disease type IIA pattern, characterized by hemorrhagic diathesis and impaired primary hemostasis 1
• The loss of large vWF multimers specifically impairs platelet adhesion and aggregation under high shear conditions 3
• Standard vWF activity assays (vWF:Rco) may appear normal despite functional defects, as closure times under high shear stress are more sensitive for detecting this abnormality 3

Gastrointestinal Angiodysplasia and Bleeding

• Angiodysplasias develop throughout the gastrointestinal tract, particularly in the small intestine, causing recurrent bleeding episodes 2, 4
• The combination of vascular malformations and impaired hemostasis from vWF deficiency perpetuates chronic blood loss 5, 4
• Bleeding may be occult or manifest as melena, often requiring capsule endoscopy or double balloon endoscopy for detection since standard upper and lower endoscopy frequently miss small bowel lesions 2, 4

Resulting Iron Deficiency Anemia

• Chronic gastrointestinal blood loss leads to progressive iron deficiency anemia that is characteristically refractory to oral iron supplementation 4
• Patients often require frequent blood transfusions to maintain adequate hemoglobin levels 2
• The anemia is typically severe, with hemoglobin levels dropping as low as 69 g/L in documented cases 4

Clinical Recognition

• The syndrome presents as the triad of aortic stenosis (detected by systolic ejection murmur on auscultation), recurrent GI bleeding, and iron deficiency anemia 1, 2
• Diagnosis requires demonstrating reduced high-molecular-weight vWF multimers by gel electrophoresis 1
• Many patients experience diagnostic delays with repeated hospitalizations and declining quality of life until the association between aortic stenosis and bleeding is recognized 5

Definitive Treatment Rationale

• Aortic valve replacement is the definitive treatment because it eliminates the high shear stress, allowing restoration of normal vWF multimer distribution and resolution of the coagulopathy 1, 2
• Following valve replacement, gastrointestinal bleeding typically resolves within months, anemia improves, and transfusion requirements cease 2, 4
• Treating gastrointestinal bleeding alone without addressing the aortic stenosis is insufficient, as the underlying coagulopathy persists 5

Important Clinical Pitfall

• Heyde's syndrome should be suspected in any patient with unexplained iron deficiency anemia refractory to oral iron who has a systolic murmur on examination, even if they have not reported overt bleeding episodes 4
• Valve dysfunction can recur even after previous valve replacement, leading to new bleeding episodes, necessitating reevaluation of valve function in patients with recurrent symptoms 5