Acquired von Willebrand syndrome in monoclonal gammopathy – A scoping review on hemostatic management

Abstract

Background Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management. Methods We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS‐MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted. Objectives To describe the clinical presentation and outcomes of different therapeutic approaches. Results Seventy‐five studies were included in the final review, for a total of 137 patients. Most patients had von Willebrand factor ristocetin cofactor activity <30 IU/dL (86.6%) and factor VIII levels <50 IU/dL (91.8%). Bleeding severity ranged from no bleeding (16.1%) to minor bleeding (46.4%) and major bleeding (37.5%). The overall clinical success rates for 1‐deamino‐8‐D‐arginine vasopressin (DDAVP), factor replacement therapy, and intravenous immunoglobulin (IVIG) were 43.8%, 33.3%, and 85.4%, respectively. The laboratory response rates for DDAVP, factor replacement therapy, and IVIG were 39.0%, 62.9%, and 88.6%, respectively. Several other treatments were also reported in small numbers, out of which myeloma‐directed therapies, plasma exchange, recombinant factor VIIa, and antifibrinolytics appeared most successful, while immunosuppressive agents were largely ineffective. Conclusion IVIG appears to be an effective treatment for AVWS‐MGUS bleeding, conferring a high clinical success rate with measurable laboratory outcomes; albeit temporary. DDAVP and factor replacement therapy may be partially successful in controlling minor bleeds, but not major bleeds. Other less commonly used agents may be effective in certain cases, although data are limited.

Daratumumab as a novel treatment for refractory acquired von Willebrand syndrome associated with monoclonal gammopathy

“…3 1-deamino-8-D-arginine vasopressin (DDAVP) and von Willebrand factor (VWF)-containing concentrates are often used first to achieve haemostatic control, albeit the response is typically unsuccessful or short-lived (lasting only hours). 4 Intravenous immunoglobulin G (IVIG) may be effective in achieving haemostatic control by neutralizing autoantibodies, resulting in a sustained increase in VWF levels but similarly, the laboratory response is temporary, thus requiring regular IVIG infusions (eg, every 21-28 days) in refractory cases. Also, IVIG is typically more effective in AVWS with immunoglobulin (Ig) G MGUS, less so for IgM MGUS.…”

Continuous-infusion von Willebrand factor concentrate is effective for the management of acquired von Willebrand disease

“…2 Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of lymphoproliferative disorder-associated aVWF. 3 MGUS-associated aVWD results from accelerated VWF clearance by monoclonal immunoglobulins (Ig). 1,3 Consequently, standard treatment protocols for congenital VWD based on intermittent bolus dosing of VWF concentrates are often suboptimal because of inadequate peak response and profoundly reduced VWF half-life.…”

“…3 MGUS-associated aVWD results from accelerated VWF clearance by monoclonal immunoglobulins (Ig). 1,3 Consequently, standard treatment protocols for congenital VWD based on intermittent bolus dosing of VWF concentrates are often suboptimal because of inadequate peak response and profoundly reduced VWF half-life. 3 Intravenous Ig (IVIG) has been used to treat aVWD, with increased efficacy in IgG MGUS compared with IgM, and an overall success rate of 85%.…”

“…1,3 Consequently, standard treatment protocols for congenital VWD based on intermittent bolus dosing of VWF concentrates are often suboptimal because of inadequate peak response and profoundly reduced VWF half-life. 3 Intravenous Ig (IVIG) has been used to treat aVWD, with increased efficacy in IgG MGUS compared with IgM, and an overall success rate of 85%. 3,4 However, maximal effect of IVIG is seen 4 days after administration, highlighting the need for faster acting therapies for actively bleeding patients.…”

“…3 Intravenous Ig (IVIG) has been used to treat aVWD, with increased efficacy in IgG MGUS compared with IgM, and an overall success rate of 85%. 3,4 However, maximal effect of IVIG is seen 4 days after administration, highlighting the need for faster acting therapies for actively bleeding patients. 4 Intermittent-bolus VWF concentrate dosing may have suboptimal efficacy in MGUS-associated acquired VWD.…”