Acquired von Willebrand syndrome has two unique profiles, study finds
Underlying blood cancers dictate severity of bleeds in rare disorder
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Acquired von Willebrand syndrome (AVWS) mainly presents as two distinct clinical and laboratory profiles, depending on the underlying blood condition, according to a new study.
“Understanding the underlying mechanism is crucial for accurate diagnosis and targeted treatment to reduce bleeding risk and improve outcomes,” researchers wrote.
The study, “Clinical and Laboratory Characterization of Acquired Von Willebrand Syndrome,” was published in the American Journal of Hematology.
AVWS typically arises in association with other underlying conditions
AVWS is a rare bleeding disorder in which the body develops a deficiency or dysfunction of von Willebrand factor (VWF), a protein that helps cell fragments called platelets stick together to form a blood clot and stop bleeding.
Unlike the inherited von Willebrand disease, the acquired syndrome arises during a person’s lifetime, typically in association with other underlying conditions, including blood cancers and related diseases, as well as autoimmune disorders. These conditions cause AVWS by altering VWF production, structure, proteolysis (breakdown), or clearance.
In this report, researchers in Italy described the clinical and laboratory features of a large group of people with AVWS, “emphasizing the relationship between bleeding [characteristics], VWF parameters, multimeric patterns, and underlying mechanisms.” Of note, VWF exists in different sizes called multimers, with the largest, called high-molecular-weight multimers (HMWM), being the most effective at promoting blood clotting.
Of the 140 adults with AVWS examined, 56% of whom were women, most (76%) had myeloproliferative neoplasms (MPNs), a group of chronic blood cancers in which the bone marrow overproduces blood cells. In MPNs, AVWS is driven by an abnormally high count of platelets, which bind to VWF and trigger its breakdown.
About one-fifth (19%) had lymphoproliferative disorders (LPDs), which are cancers or abnormal growth of lymphocytes, a type of white blood cell. Here, LPD patients exhibit increased clearance of VWF from the bloodstream.
Of the remaining participants, three (2.1%) had an autoimmune disease (one with lupus, two with ulcerative colitis), one (0.7%) had severe aortic stenosis, or narrowing of a heart valve, and one (0.7%) had prostate cancer. Three patients (2.1%) had no identifiable underlying condition.
Rates, severity of bleeding differed between two main groups
At least one bleeding symptom was observed in 70% of the group. The most common symptoms were skin bleeds (20%) and nosebleeds (16%), followed by minor wound bleeding (9%), oral cavity bleeding (6%), and digestive tract bleeding (5%).
However, the rates and severity of bleeding differed markedly between the two main groups. That is, a clinically significant bleeding history was more than four times higher in those with LPD than those with MPN (58% vs. 13%). And, more LPD patients experienced skin bleeds (38% vs. 16%), nosebleeds (38% vs. 11%), and gastrointestinal bleeds (21% vs. 1%) than MPN patients.
In line with those findings, VWF protein levels and platelet-binding activity were lower than normal in both groups, but much more severely in LPD patients. And while VWF clearance from the bloodstream was normal in MPN patients, it was strikingly elevated in LPD patients. This group also showed a pronounced loss of HMWM.
Taken together, these findings support an individualized, mechanism-oriented approach to the diagnosis and management of AVWS in hematologic disorders.
In LPD patients, impaired VWF platelet-binding activity was significantly associated with more severe bleeding, as assessed using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool. In contrast, no significant associations were identified in the MPN group.
Finally, the researchers tested 20 patients with suspected immune-mediated disease for antibodies that mistakenly target VWF. Of these, six (30%) tested positive, five with LPDs and one with lupus. No anti-VWF antibodies were detected in MPN patients. The team suggested that these antibodies were most likely non-neutralizing, meaning they did not directly block VWF function but instead tagged it for accelerated removal from the bloodstream.
“This study on a large cohort of patients provides clinically relevant insights into AVWS associated with hematologic disorders,” the researchers wrote. “Taken together, these findings support an individualized, mechanism-oriented approach to the diagnosis and management of AVWS in hematologic disorders.”
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