Laboratory Diagnosis of Acquired von Willebrand’s Syndrome

Acquired von Willebrand syndrome (AVWS) is a rare disorder in which laboratory findings and clinical symptoms mimic various types of von Willebrand disease (VWD). It may be suspected in a patient with abnormal VWD tests and no previous history of excessive bleeding, who has one of the disorders and conditions listed in Table 135.1 or one with a similar mechanism. The International Registry on AVWS ( http://www.intreavws.com/ ) lists over 100 cases, only two of which are idiopathic. More than 300 cases have been reported in the literature. AVWS may be due to the presence of an autoantibody, adsorption of von Willebrand factor (VWF) by cells or surfaces, increased VWF proteolysis or clearance, or decreased or aberrant VWF production. Autoantibodies specific to VWF may inhibit its function or form immune complexes that are cleared from the circulation. Nonspecific antibodies may also cause VWF clearance. VWF may be adsorbed to tumor cells, lymphocytes, plasma cells, or activated platelets. In congenital or acquired cardiac defects, AVWS may result from adsorption of high-molecular-weight (HMW) multimers to aberrant structures, or from increased proteolysis due to high shear stress, and often resolves with surgical correction. Hypothyroidism leads to decreased VWF production, which is restored by treatment. VWF propeptide (VWFpp), a marker for VWF synthesis, is decreased in hypothyroidism. It is usually normal in AVWS from other causes, often leading to an increased VWFpp/VWF:Ag ratio, indicating normal synthesis and subsequent loss.