Hemorrhage is a well-known complication of essential thrombocythemia (ET) and polycythemia vera (PV), but evidence-based data on its management and prevention are lacking to help inform clinicians. In this review, appropriate published data from the past 15 years regarding bleeding epidemiology, classification, location, and risk factors are presented and discussed. Research was conducted using the Medline database. The bleeding classifications were heterogeneous among the collected studies. The median incidences of bleeding and major bleeding were 4.6 and 0.79% patients/year, in ET patients and 6.5 and 1.05% patients/year in PV patients, respectively. The most frequent location was the gastrointestinal tract. Bleeding accounted for up to 13.7% of deaths, and cerebral bleeding was the main cause of lethal hemorrhage. Thirty-nine potential risk factors were analyzed at least once, but the results were discrepant. Among them, age >60 years, bleeding history, splenomegaly, myeloproliferative neoplasm subtype, and platelet count should deserve more attention in future studies. Among the treatments, aspirin seemed to be problematic for young patients with ET (especially CALR-mutated ET patients) and anagrelide was also identified as a bleeding inducer, especially when associated with aspirin. Future studies should analyze bleeding risk factors in more homogeneous populations and with common bleeding classifications. More tools are needed to help clinicians manage the increased risk of potentially lethal bleeding events in these diseases.

Acquired von Willebrand syndrome is a rare bleeding disorder often secondary to an underlying lymphoproliferative disorder. We report a case in whom response of both the acquired von Willebrand syndrome and smoldering multiple myeloma persist 14 months after daratumumab treatment discontinuation. K E Y W O R D Sacquired von Willebrand syndrome, bleeding, daratumumab, smoldering multiple myeloma

Introduction Acquired von Willebrand syndrome (AWS) is a rare and potentially life‐threatening bleeding disorder. AWS is primarily associated with lymphocyte‐related disorders (AWS‐LRD), such as lymphoma and IgM monoclonal gammopathy of undetermined significance (MGUS), and plasmocyte‐related disorders (AWS‐PRD), such as non‐IgM MGUS and myeloma. Symptomatic treatments are important to control and prevent bleeding, but AWS‐LRD and AWS‐PRD can only be cured by targeting the responsible clonal cell. No reviews exist on this specific subgroup of AWS. Aim We performed a literature review to help manage these rare cases. Method Thirty‐two AWS‐PRD and 43 AWS‐LRD cases with data on malignancy treatment were reported in 56 articles from the Medline database. Results LRDs were exclusively indolent and primarily associated with IgM monoclonal compounds. LRDs and PRDs may be treated because of severe bleeding symptoms, but severe VWF deficiency did not necessarily correlate with severe bleeding. Immunosuppressive drugs in AWS‐PRD, including rituximab, provided an overall response rate of AWS (AWS‐ORR) of 30% (3/10), including short responses. Anti‐myeloma drugs provided an AWS‐ORR of 71.4% (20/28), with long‐lasting remissions. Bortezomib was the most commonly used drug and provided an AWS‐ORR of 66.7% (6/9), including therapeutic associations with other anti‐myeloma drugs. Autologous and allogeneic stem cell transplantation was performed in eight and two patients, respectively, and some details on the management of AWS during these procedures were provided. Rituximab in AWS‐LRD provided an AWS‐ORR of 60% (3/5), and a chemotherapy + rituximab regimen increased the AWS‐ORR to above 50%. Bleeding syndrome in AWS‐PRD and AWS‐LRD generally improved prior to AWS biological improvement. Conclusion Long term remission of AWS due to lymphoid neoplasms is attainable by treating the underlying clonal cell. Some data and recommendations are provided to help answer difficult questions, including treatment timing, choice of drug, and the timing of evaluations and treatment changes.

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