Presentation Details
| Acquired von Willebrand Syndrome in Monoclonal Gammopathy of Undetermined Significance: A Focus on Response to Treatment with IVIG Tanna Tan1, Rajiv K.K.Pruthi2, Aneel A.Ashrani2, Meera Sridharan2. 1Division of Internal Medicine, Mayo Clinic, Rochester, MN, USA.2Division of Hematology/Oncology, Mayo Clinic, Rochester, MN, USA |
Abstract
Introduction: Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with an established association with monoclonal gammopathies. Intravenous immunoglobulin (IVIG) has been demonstrated to be efficacious in the treatment of AvWS associated with MGUS (AvWS-MGUS) and can lead to a sustained elevation in von Willebrand factor (vWF) levels after infusion. Objectives: Characterize the demographics and clinical presentation of AvWS-MGUS and assess response to IVIG treatment in AvWS-MGUS. Methods: The electronic medical record was queried for patients evaluated at Mayo Clinic from January 2003 to March 2023 with diagnosis of aVWS and MGUS. 68 patients were identified. Charts were reviewed to determine eligibility. Exclusion criteria included a diagnosis of multiple myeloma, smoldering myeloma, amyloidosis or Waldenström’s macroglobulinemia; no confirmed MGUS; or VWF results not available at diagnosis. Data on patient demographics, laboratory and clinical presentation, initial treatments, and IVIG response were collected. Bleeding presentations were assessed using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT). Baseline laboratory findings and bleeding presentation were compared between patients receiving and not receiving IVIG. Clinical response to IVIG was defined as cessation of active bleeding or prophylaxis of further bleeding events, including post-operative bleeding. Laboratory response to IVIG was characterized by sustained increase in VWF:Ag, VWF activity, and FVIII activity, or clinician-determined appropriate elevation in these levels. Results: 37 patients met study criteria. Median age was 64.89 years. 36 patients had bleeding history at time of diagnosis. Most common bleeding symptoms were cutaneous (n=14), post-procedural (n=13), and gastrointestinal bleeding (n=11). Median M-spike was 0.5 (0.1-3.190) mg/dL (n=30). 7 patients did not have an evaluable M-spike. Median VWF:Ag, VWF activity, and FVIII levels at diagnosis were 19 (6-587)% (n=37), 24 (6-537)% (n=24), and 22 (6-330)% (n=36), respectively. VWF multimers were analyzed in 36 patients and were normal in 18.9%. Of 29 patients with VWF multimer abnormalities, the most common finding was reduced highest molecular-weight VWF multimers (n=18). 25 patients required hemostatic therapy including DDAVP (n=7), Humate-P (n=20), and anti-fibrinolytics (n=7). 21 patients (57%) received IVIG (table 1); indications included control of bleeding (n=6), and bleeding prophylaxis for surgery (n=6) and procedures not requiring general anesthesia (n=3). Median ISTH-BAT was 5 (range 0-11) in those receiving IVIG versus 4 (range 0-7) in those not receiving IVIG (p=0.065). Patients receiving IVIG had lower baseline VWF:Ag, VWF activity, and FVIII levels (table 1). Median change in VWF:Ag, VWF activity, and FVIII was 59% (13-528%) (n=20), 43% (6-251%) (n=14), 82% (21-218%) (n=19) at 16 hours (3-72hrs) after receiving IVIG. Both clinical and laboratory response rate to IVIG was 81%. Despite high response rates, 9 patients required additional treatments following IVIG (figure 1). 10 patients not receiving IVIG required desmopressin (n=1), Humate-P or Vonvendi (n=7), anti-fibrinolytics (n=1), or immunosuppression (n=1); these treatments were effective in 80% of the patients. Conclusions: In this large single-center cohort study assessing IVIG response in AvWS-MGUS, IVIG was typically used for bleeding refractory to VWF concentrate and was associated with a good initial clinical and laboratory response.
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