IWWM-12 2024 | Acquired von Willebrand disease in Waldenström’s macroglobulinemia: diagnosis and treatment

Dr Karan Chohan and our group actually looked at von Willebrand factor, von Willebrand disease, acquired von Willebrand disease in Waldenstrom’s macroglobulinemia. And we do see it is a rare disease, especially important for Waldenstrom’s macroglobulinemia because Waldenstrom’s has a pentameric IgM gammopathy, IgM is a pentameric protein. And because of that, there can be an acquired VWD happening because of decrease of high molecular weight multimers in the von Willebrand factor. So in that setting, patients can develop an acquired von Willebrand syndrome, which leads to bleeding throughout their disease course. So we found that although minority of patients do acquire the acquired von Willebrand syndrome some patients may have clinically significant bleeding. So for an example in our cohort few patients had significant GI bleed that requires an intervention. Some patients also had intracranial bleed that required an intervention as well. So overall survival was not different between this or none of these conditions were giving the mortality for these patients. However, as a clinician, it is very important for us to be cognition about this, this acquired von Willebrand disease in patients with Waldensrom’s macroglobulinemia. Especially, I would suggest that a few important things to remember, if the patient has very high IgM level and has clinically non-significant bleeding at the time of diagnosis such as you know epistaxis bleeding from the nose petechiae or something like that please have acquired von Willebrand syndrome in the differential diagnosis because these patients can indeed develop hyperviscosity syndrome from Waldenstrom’s macroglobulinemia which can manifest with coagulation abnormalities as well. However, one should definitely in such patients with high IgM level and clinically subtle bleeding symptoms, we do need to check for von Willebrand disease. So coagulation factors, von Willebrand factor and its activity level should be tested including factor VIII. And if it is abnormal, these patients should be treated. When it comes to treatment, of course, treating Waldenstrom’s macroglublinemia and decreasing that IgM will treat underlying acquired von Willebrand disease. However, in our cohort, many of the patients actually do require factor replacement or help with blood clotting were required, especially before surgical procedure. So providers who are managing patients with Waldenstrom’s macroglobulinemia, do need to consider, you know, ask the patients about the bleeding abnormalities. Ask the patients about nose bleeds and so forth. And if positive or having a very high IgM level, please do check for coagulation abnormalities, including the von Willebrand levels and the factors, factor VIII. And if they’re abnormal, you don’t necessarily have to replace in the absence of significant GI bleed or, sorry, significant bleeding or patient requiring like a suspected surgical procedure that have high bleeding risk. However, you should need to monitor this while patient receiving treatment because with the treatment, this will be getting better. But if the patient has very clinical significant bleeding or requiring any surgical procedures, we need to replace the factors and make sure the factor VIII and von Willebrand levels are within normal limits. And the other thing is, if these patients have significant bleeding risk, with acquired von Willebrand disease, I will have reservations in commencing these patients with ibrutinib or BTK inhibitors because that will increase the risk of bleeding. So these patients are best treated with chemoimmunotherapy such as bendamustine and rituximab instead of BTK inhibitors in the setting of acquired von Willebrand disease.