Bleeding in the Setting of Lymphoma, with a Focus on Waldenström Macroglobulinaemia

Bleeding symptoms are common in haematological malignancies, with 26% experiencing minor to moderate bleeding and 6% experiencing major or fatal haemorrhages. However, bleeding is underreported and remains poorly understood in this patient cohort. This book chapter will discuss the known contributors to bleeding in haematological malignancies, including possible platelet dysfunction, common therapies that increase bleeding risk, limitations of tests evaluating bleeding in the diagnostic laboratory and future directions for research in this field. This book chapter will particularly focus on Waldenström Macroglobulinaemia (WM), a rare, low-grade, incurable B-cell lymphoma, which offers interesting insights into bleeding in haematological malignancies, as it is characterised by 1) bone marrow (BM) and organ infiltration by proliferating lymphoplasmacytoid B cells, and 2) immunoglobulin (Ig) M hypersecretion. Interestingly, bleeding has been observed in WM and other haematological malignancy patients who do not have thrombocytopenia, acquired von Willebrand syndrome (AVWS), disseminated intravascular coagulation (DIC), blood hyperviscosity, cryoglobulinaemia or hyperfibrinolysis, implying that other potential contributors exist. One alternative contributor is a possible acquired platelet lesion, caused by disruption to the BM microenvironment and megakaryocyte (MK)-mediated platelet production by infiltrating malignant cells, or by acquisition of common driver mutations in the megakaryocytes (MKs). The resulting platelets could have altered adhesion, activation and aggregation responses due to the loss of important surface receptors, such as glycoprotein (GP) Ibα and GPVI; or altered intra-platelet signalling due to the acquisition of mutant constitutively active signalling proteins. Additionally, bleeding is exacerbated in haematological malignancies by standard and novel therapies, and the treatment of comorbidities with anticoagulants and antiplatelets further increases this risk. Therefore, it is important to better understand the molecular mechanisms behind bleeding in haematological malignancies, to stratify patients based on bleeding risk, aid in clinical decisions surrounding therapy, minimise bleeding morbidity and improve patients’ quality of life.