To describe a case report of a patient with monoclonal gammopathy of undetermined significance (MGUS) who progressed to Acquired von Willebrand syndrome (AVWS) and was successfully treated with bortezomib.

Case report with literature review.

A 54-years-old woman presented at our center to investigate an M-spike. She had been treated for chronic kidney disease due to glomerulonephritis for eight years and was on peritoneal dialysis waiting for a kidney transplant. During laboratory workup, a serum M-protein (0.3 g/dL) was detected by protein electrophoresis and a monoclonal IgG kappa was identified. After one year of follow-up, and with stable M-protein levels, the patient started complaining of increased bleeding from minor wounds, bruises in inferior limbs and repeated episodes of epistaxis. The patient had no personal or family history of bleeding disorders. Laboratory testing included normal blood and platelet counts, normal prothrombin and thrombin time but increased activated partial thromboplastin time (APTT ratio 1.62). Mixing study results showed APTT correction. Factor VIII coagulant activity (FVIII:C) was 12% but no inhibitor was detected. Von Willebrand factor antigen (vWF:Ag) was 10% and ristocetin cofactor activity (vWF:RCo) was 3%, with a vWF:RCo/vWF:Ag ratio of 0.3. Given the absence of previous personal and family history of bleeding and the diagnosis of MGUS, the diagnostic hypothesis of AWVS was made. To confirm this hypothesis, we performed a recovery test after infusion of von Willebrand factor (vWF 50 UI/kg), which results were suggestive of increased vWF clearance. The patient required treatment only after three years of AVWS diagnosis due to severe lingual hematoma. She was treated with two units of packed red blood and immunoglobulin (0.4g per kg for five days), with successful bleeding control. vWF:Ag, vWF:RCo and FVIII:C levels were also increased but returned to baseline values after three weeks. Because the patient was scheduled to undergo a kidney transplantation and the high risk of bleeding could lead to graft loss, it was decided to treat the MGUS-associated AVWS. She was treated with three cycles of dexamethasone 20 mg and cyclophosphamide 300 mg with no response. A second line treatment was started with dexamethasone 12 mg and bortezomib 1.5mg/m2 for a total of five cycles. After the end of the treatment, APTT, vWF:Ag, vWF:RCo results normalized and monoclonal paraprotein was eradicated. The patient was submitted to a kidney transplantation without bleeding complications. Two years after the end of the treatment, she remains in remission, with undetectable monoclonal paraprotein and normal coagulation and VWF tests.

MGUS-associated AWVS is a rare bleeding disorder, and few data is available on the best treatment approach. We reported a case that transiently responded to immunoglobulin. This response, however, was not sufficient to warrant hemostatic levels of vWF required for kidney transplantation. Treatment of MGUS with bortezomib and dexamethasone led to eradication of the M-spike and normalization of the coagulation parameters. This response was durable, as the patient remains in remission of both MGUS and AWVS two years after the end of the treatment. This particular case highlights the importance of treating the underlying cause of the coagulopathy once the remission of AVWS only occurred after monoclonal gammopathy was controlled.