Gastrointestinal Angiodysplasia and Acquired von Willebrand Syndrome: A Review of an Enigmatic Association

Review Article

Gastrointestinal Angiodysplasia and Acquired Von Willebrand Syndrome: A Review of an Enigmatic Association


Renu Saxena and Prashant Sharma

Affiliation: Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India

Submission date: 15th June 2009, Revision date: 29th June 2009, Acceptance date: 14th August 2009


ABSTRACT

Von Willebrand disease (VWD), the commonest inherited bleeding disorder, is characterized by reduced levels and/or abnormal function of von Willebrand factor (VWF). It may rarely be acquired (von Willebrand syndrome, VWS) in association with a variety of underlying conditions including myeloid, lymphoid and nonhematologic malignancies, autoimmune disorders, specific pharmaceutical agents, valvular heart defects and endocrine abnormalities.
Gastrointestinal bleeding due to intestinal angiodysplasia is a well‐documented complication of VWD as well as the acquired VWS, predominantly seen in elderly patients. Its high prevalence in disease subtypes associated with reduced or absent high molecular weight (HMW) VWF multimers suggests that the specific loss of these molecules is the primary pathologic event in abnormal hemostasis under high shear stress blood flow conditions. This link, first postulated specifically by Warkentin and colleagues, has now been borne out by both laboratory and epidemiological studies.

VWF HMW multimer deficiency also provides a plausible link between senile aortic stenosis and gastrointestinal bleeding in Heyde syndrome. Enhanced proteolysis of HMW multimers by the shear‐dependent VWF cleaving metalloproteinases as well as avid platelet binding of uncoiled HMW multimers results in accelerated clearance from circulation. The resultant deficiency mimicking VWD type 2A frequently resolves after surgical correction of the cardiac defect.

The diagnosis and management of occult gastrointestinal bleeding from angiodysplasia in VWD or VWS are often challenging as is differentiating the acquired from the inherited forms of the disorder. Multiple therapeutic approaches have been tried with varying degrees of success.

Keywords: acquired von Willebrand disease, angiodysplasia, aortic stenosis, Heyde syndrome, high molecular weight multimers, high shear stress, occult gastrointestinal bleeding
Correspondence: DrRenu Saxena, Professor and Head, Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India