PO126 | HIGH-DOSE INTRAVENOUS IMMUNOGLOBULINS FOR LONG-TERM PREVENTION OF RECURRENT GASTROINTESTINAL BLEEDING IN A PATIENT WITH ACQUIRED VON WILLEBRAND SYNDROME ASSOCIATED WITH MGUS

R. Benedetti¹, G. Quintavalle², V. Della Corte¹, M.I. Tassoni¹, B.M. Roccon¹, D. Imberti¹, A. Coppola² | ¹Centro Emostasi e Trombosi, Medicina Interna, Azienda USL di Piacenza, Italy; ²SSD Centro Hub Emofilia e Malattie Emorragiche Congenite, Azienda Ospedaliero-Universitaria di Parma, Italy

Background. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated with various underlying conditions and diverse pathogenic mechanisms, resulting in functional interference or increased clearance/degradation of von Willebrand Factor (VWF). Recurrent gastrointestinal (GI) bleeding is a common and challenging symptom, particularly in elderly patients. While treating the underlying disorder remains the only potentially curative approach, hemostatic therapies -including desmopressin, VWF/Factor VIII (FVIII) concentrates, and antifibrinolytic agents- show variable efficacy in controlling acute bleeding. Other reported interventions include plasmapheresis, recombinant activated factor VII, and high-dose intravenous immunoglobulins (HDIVIg). The latter have proven effective in patients with AVWS associated with IgG monoclonal gammopathy of undetermined significance (MGUS). Here, we report the long-term management using HDIVIg in a woman with recurrent GI bleeding secondary to AVWS and MGUS.
Case Report. A 76-yr-old woman presenting with recurrent GI bleeding and severe anemia underwent multiple endoscopic examinations, including video capsule endoscopy, which revealed active bleeding in the duodenum and proximal jejunum. Repeated clip placements and adrenaline infiltrations were unsuccessful. Consequently, surgery to resect the fourth portion of the duodenum and proximal jejunum was needed. However, life-threatening postoperative bleeding occurred, requiring multiple red blood cell transfusions. Previous documentation of Lupus Anticoagulant led to overlook a persistently prolonged aPTT (ratio 1.7). Following the postoperative complications, further testing revealed FVIII (17%) and VWF deficiencies (antigen 16%, ristocetin cofactor activity 19%). A low-concentration IgG-MGUS, known since 2003, was also noted. Suspecting AVWS, the patient was treated with VWF/FVIII concentrates, which provided only partial and transient bleeding control. High doses (40–50 IU/kg) every 12–24 hours failed to maintain VWF activity levels above 20%, despite adequate FVIII levels. Treatment with HDIVIg (1 g/kg for 2 days) was then initiated, resulting in the prompt normalization of FVIII and VWF levels (>200% after 3 days). No recurrence of bleeding or anemia was observed and HDIVIg administration was repeated after 4 weeks. Hematological consultations repeatedly ruled out the indication for direct MGUS treatment. To maintain clinical stability, HDIVIg cycles were administered every 5 weeks for 8 months, then extended to 6 and later 7 weeks. The patient has now been followed for 26 months. Although normal VWF and FVIII levels are only maintained for approximately 3 weeks post-infusion, she has remained free of clinically evident GI bleeding with stable hemoglobin levels. The IgG-MGUS concentration was substantially unchanged. Recently, long-acting octreotide was introduced as an alternative approach for prevention of GI bleeding recurrence.
Conclusions. HDIVIg was confirmed to be effective in this patient with severe GI bleeding due to AVWS associated with MGUS. Data regarding long-term management in this setting remain scarce. Our experience suggests that HDIVIg administration intervals can be successfully extended. The clinical benefit may persist beyond the hemostatic effects related to the actual VWF levels, potentially due to favorable anti-angiogenic modulation resulting from partially restored VWF concentrations.