Acquired Von Willebrand Syndrome

Here is a new message from Kim Kinney at Clarian in Indianapolis. I think you’ll agree, she always has interesting cases.

Hi George, We have a very interesting von Willebrand disease case.  An 83 yo gentleman was admitted to our local VA for repair of a stomach lesion and had bleeding complications post-surgury.  He also has had issues with GI bleeding in the past.  We did an inital mix and the PTT of 45.2 seconds corrected immediately and did not show prolongation with time/temp.  His PFA was very prolonged with both the ADP and EPI cartridges but he did have a low crit.  We performed a factor VIII assay which was 12%, ristocetin cofactor was < 13% and his vWF antigen was 18%!  Multimers are being sent for analysis. We were thinking a possible acquired von Willebrand due to his age.  The hematologist is interviewing the patient again and is wondering if this could not be congenital due to his bleeding history.  Is there a genetic way to distinguish congenital from acquired von Willebrand disease?  Or is it usually based on family history and lab data?  I will most certainly look in to the von Willebrand modules!

Hi, Kim. Thanks for your interesting case. Unfortunately, it may be difficult for you to distinguish definitively between inherited von Willebrand disease (VWD) and acquired von Willebrand syndrome (AVWS).

In the recently posted von Willebrand disease modules I devoted only one slide to AVWS because it is relatively rare, so this gives me an opportunity to provide additional information. I’m using the 2008 NHLBI von Willebrand disease report cited in the module for most of my information.

AVWS may be caused by autoimmune clearance or inhibition of von Willebrand factor (VWF), increased shear-induced VWF proteolysis or increased VWF binding to platelets or other cells.

Autoimmune VWF clearance may accompany lymphoproliferative disorders, monoclonal gammopathies and autoimmune disorders. Autoantibodies are actually detected in about 20% of people suspected of AVWS, which may just mean our assays are insensitive or the autoantibody is rapidly cleared.

VWF shear may be caused by ventricular septal defects, aortic stenosis and primary pulmonary hypertension. VWF is distorted by the physical condition, exposing it to VWF-cleaving protease.

VWF may bind platelets or other cells in myeloproliferative disorders such as essential thrombocythemia or chronic myelocytic leukemia. VWF activity may be restored when the platelet count is reduced.

In most instances the VWD profile may resemble VWD type 2 with moderately decreased VWF ristocetin cofactor (VWF:RCo) activity and relatively normal VWF antigen (VWF:Ag) and factor VIII levels. Large multimers are decreased. The fact that your patient has a type 1 profile may indicate inherited VWD, and the multimeric analysis may help.

Blood Center of Wisconsin provides DNA sequencing, mostly devoted to subtyping the domains associated with VWD type 2. You may want to discuss an investigation with Dr. Montgomery, director ot their hemostasis laboratory. I suspect you could rule in a type 2 mutation if found in sequencing, but could have difficulty ruling out inherited VWD.

DDAVP or Humate P usually help manage AVWS, and they must be closely monitored using the VWF:RCo, as the half-life could be shortened. The increased therapeutic demand could be a clue that distinguishes AVWS from VWD, however some forms of VWD type 1 are caused by increased VWF consumption. These type 1 patients could also have a short therapeutic half-life.

Finally, the best way to conclude your patient has inherited VWD is to test his first-degree kindred for the condition and observe the inheritance pattern.

Again, thanks for your question. If there is a more definitive answer, perhaps one of our readers can respond. Meanwhile, be sure to check out our latest modules and record your participation through CACMLE. Geo