From the Research
In Heyde's syndrome, von Willebrand factor (vWF) antigen activity is typically normal or elevated, but the high molecular weight multimers of vWF are deficient, as seen in a case report where vWF antigen levels were 1.26 IU/ml, which is within normal limits 1. This condition involves an acquired form of von Willebrand disease type 2A that occurs in patients with aortic stenosis. The mechanism involves the high shear stress created by blood flowing through the narrowed aortic valve, which causes elongation and unfolding of vWF multimers.
- These unfolded multimers become susceptible to proteolysis by the enzyme ADAMTS13, leading to a reduction in the most hemostatically active high molecular weight multimers while overall vWF antigen levels remain normal or elevated.
- This selective deficiency explains the paradoxical combination of bleeding (typically gastrointestinal bleeding from angiodysplasia) and a stenotic heart valve condition.
- Laboratory testing in these patients often shows normal or elevated vWF antigen levels but decreased vWF activity in functional assays, creating a characteristic discrepancy between antigen and activity measurements, as noted in a study where the vWF:Rco activity was normal, but the closure times were abnormal 1.
- Aortic valve replacement typically reverses these hematologic abnormalities by eliminating the high shear stress environment, as demonstrated in a case report where a patient's bleeding subsided after aortic valve replacement 2. However, it is essential to note that the prevalence of acquired von Willebrand deficiency in Heyde's syndrome may be debated, and some cases may not show this deficiency, as reported in a study where a patient with Heyde's syndrome had normal vWF activity 3. The most recent and highest quality study on this topic is from 2024, which provides a comprehensive review of the molecular mechanisms involved in the development of Heyde's syndrome and discusses current diagnostic and treatment approaches 4.
- The study highlights the importance of considering Heyde's syndrome in patients with aortic stenosis and gastrointestinal bleeding, even if vWF activity is normal.
- It also emphasizes the need for a multidisciplinary approach to diagnose and treat this complex condition. In terms of treatment, aortic valve replacement is the pivotal strategy to achieve long-term resolution of bleeding recurrences, as noted in a study where TAVR was a valuable option for high-risk patients 5. Therefore, in patients with Heyde's syndrome, vWF antigen activity is typically normal or elevated, but the high molecular weight multimers of vWF are deficient, and aortic valve replacement is the recommended treatment to reverse the hematologic abnormalities and prevent further bleeding complications 4.