This is from Demetra "Toula" Castillo, Carolinas HealthCare. Can someone please explain to me how someone with a bleeding disorder can get a PE ? She has type 2M VWD and takes Stimate for localized bleeds and gets monthly infusions of Humate-P. She also has endometriosis due to the VWD. Her last infusion was 3 weeks ago, but was treated with stimate 8 hours ago.
From George: Thank you, Toula, VWD subtype 2M is a qualitative VWD in which the VWF concentration is normal to slightly reduced, the multimer pattern is near-normal, but there is a mutation that reduces VWF adhesion to the platelet GPIb receptor. Subtype 2M has been described as being less than 5% of VWD cases, but Dr. Emanual Favaloro and several other experts think it is more prevalent but just gets routinely misdiagnosed as type 1 or subtype 2A. There are no reports that relate VWD 2M to venous thromboembolic disease, but I suspect there just aren't enough reportable cases. The source of thrombosis could be anatomic rather than being related to a coagulation disorder, however the Girolami article cited below implicates replacement therapy in 35 cases. I speculate the use of Humate P could be the answer. In VWD subtype 2M the FVIII activity is close to normal, and Humate P provides 1 part FVIII to 2.4 parts VWF , perhaps pushing the FVIII level to above the reference interval limit. The Stimate could have the same effect. Your friend and her doctor might want to consider a newly (2015) approved recombinant VWF , Vonvendi, from Shire, which is pure VWF.
From Toula: Yes, I read Girolami's article and suspect that the Humate-P or Stimate may have caused this. I'm also not ruling out a vascular/anatomic defect, but how can that be detected? She's had a CT scan of her lungs and a Doppler of her legs already--wouldn't it show a vascular or anatomic defect? I am also investigating the possibility that there is a genetic or gynecological influence. She's 38 years old, and doesn't have some of the risk factors associated with VTE , but what hasn't been determined is whether she has an underlying FVL , PTG20210, or MTHFR. Finally, I've been reading that gynecological impairments can also induce simultaneous hypo- and hypercoagulable conditions. PCOS has been implicated mostly, but endometriosis has also been seen in a few cases. She has endometriosis, so I'm not ruling that out.
Thank you Toula, please keep us informed of developments, and let's see what some of our participants have to say. Geo.
Girolami A, Cosi E, Tasinato V, Peroni E, Girolami B, Lombardi AM. Pulmonary embolism in congenital bleeding disorders: intriguing discrepancies among different clotting factors deficiencies. Blood Coagul Fibrinolysis. 2016;27:517–25.