Abstract Number: PB0938
Meeting: ISTH 2021 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » VWF and von Willebrand Factor Disorders - Clinical Conditions
Background: Acquired Von Willebrand Syndrome (AVWS) is an acquired coagulopathy, often associated to an underlying disorder. The diagnosis is not easy and relies on a negative familial and personal clinical hemorrhagic history and a late onset in life of bleeding symptoms, associated with a laboratory pattern for Von Willebrand Disease (VWD).
Aims: Aim of this study is to describe the experience on diagnosis and management of AVWS patients (pts) in two Italian centers.
Methods: Between 2004-2020 we have diagnosed and managed 14 pts [8F, 6M; median age 62.45 years (45.4-85.9)] affected by AVWS. Determination of coagulation parameters, including FVIII, were carried out on an automatic coagulometer (ACL Top 700, Werfen). VWF:antigen (VWF:Ag) and VWF:activity (VWF:RCo) were measured by chemiluminescence assays (HemosIL AcuStar, Werfen). VWF propeptide (VWFpp) level was measured by ELISA immunoassay (Sanquin, Amsterdam, NL). The screening for VWF:RCo inhibitor was made utilizing mixing studies
Results: At diagnosis, for all pts, we observed the results showed in table 1. VWFpp and multimers were studied just in 9 pts. Except VWFpp median level, all other VWF-related median parameters were significantly reduced. VWFpp/VWF:Ag ratio was significantly higher in all 9 studied pts; multimers were absent in 6 and normal in 2; in 1 patient just LMW multimers were present. All the pts did not have either a family or past personal history of bleeding symptoms. Thirteen/14 cases showed a concomitant disorder, one case was idiopathic. In table 2, therapies either for underlying disorders if present or AVWS, and outcomes are shown.
| Table 1. Clinical and laboratory characteristics of patients | |
| Median VWF:Ag (n.v. blood group 0: 41-101%; no 0: 50-130%) |
15% (range 1.6-51%) |
| Median VWF:RCo (n.v. blood group 0: 41-97%; no 0: 52-124) |
13% (range <6.25-33%) |
| Median FVIII:C (n.v.58-130%) |
19.2% (range 2.1-53%) |
| Median VWFpp (n.v. 70-140) |
81.5 % range 42.9-154.3 |
| Median VWFpp/VWF:Ag (n.v. ratio <3.0) |
20.0 |
| VWF:RCo inhibitor (searched in 4 cases) | 3 negative, 1 positive |
Clinical and laboratory characteristics of patients
| Table 2. Management of the patients with lymphoproliferative disorders |
||
| Type | Treatment | Response |
| Gastric B cell MALT lymphoma 1 patient |
Rituximab | Complete remission of lymphoma and AVWS |
| Waldenstrom Disease 1st patient |
R-CVP Ibrutinib |
After 2nd line, stable lymphoproliferative disease and persistent AVWS |
| Waldenstrom Disease 2nd patient |
Rituximab After two years for disease progression: Rituximab+-Bendamustine |
Partial response Persistent AVWS and partial response of lymphoma |
| Indolent B cell lymphoma 1 patient |
Watch and wait strategy Rituximab |
Complete remission of lymphoma and AVWS |
| Strategies to manage AVWS in all patients | ||
| Type of disorder | Treatment | Response |
| MGUS 1 patient |
Prednisone + cyclophosphamide and then high dose immunoglobulins | No response to either therapies |
| MGUS 3 patients |
Infusion of high dose immunoglobulins (2 cases are under chronic treatment with Iv Ig every 6-8 weeks) |
Transient CR as regard VWD laboratory parameters |
| MGUS 4 patients |
No treatment |
|
| Breast cancer 1 patient |
Prednisone | Response to bleeding’s symptoms |
| Idiopathic AVWS 1 patients |
Prednisone At relapse Prednisone + cyclophosphamide |
CR on VWD laboratory parameters CR on VWD laboratory parameters |
Management of the patients with lymphoproliferative disorders
Conclusions: AVWS is a rare syndrome, probably underdiagnosed. AVWS must be suspected whenever a patient presents with a late onset in life of bleeding symptoms associated to laboratory characteristics compatible with VWD. The VWFpp/VWF:Ag ratio could be a valuable biomarker to be considered to help the diagnosis.
To cite this abstract in AMA style:
Ferretti A, Baldacci E, Lancellotti S, Basso M, Barone F, Pallotta A, Lapietra G, Sacco M, Chistolini A, De Candia E, Santoro C. Acquired von Willebrand Disease: The Diagnosis and Management of an Underdiagnosed Coagulopathy [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/acquired-von-willebrand-disease-the-diagnosis-and-management-of-an-underdiagnosed-coagulopathy/. Accessed December 7, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/acquired-von-willebrand-disease-the-diagnosis-and-management-of-an-underdiagnosed-coagulopathy/