What is the association between Waldenström's (Waldenström's macroglobulinemia) and bleeding?

From the Guidelines

Waldenström's macroglobulinemia is associated with an increased risk of bleeding due to hyperviscosity syndrome, acquired von Willebrand disease, thrombocytopenia, and cryoglobulinemia, and management includes treating the underlying disease with chemotherapy regimens and supportive measures to reduce bleeding risk. The primary cause of bleeding in Waldenström's macroglobulinemia is hyperviscosity syndrome, which results from high levels of IgM paraprotein and can impair platelet function and interfere with coagulation factors 1. Additionally, patients with Waldenström's macroglobulinemia may develop acquired von Willebrand disease, thrombocytopenia from bone marrow infiltration, and cryoglobulinemia, all contributing to bleeding risk.

Some key points to consider in the management of bleeding risk in Waldenström's macroglobulinemia include:

• Monitoring for signs of bleeding such as epistaxis, gingival bleeding, easy bruising, or gastrointestinal bleeding
• Treating the underlying disease with chemotherapy regimens like bendamustine plus rituximab or ibrutinib to reduce IgM levels
• Using plasmapheresis to rapidly reduce IgM levels in cases of acute bleeding with hyperviscosity
• Providing supportive measures such as platelet transfusions for severe thrombocytopenia and avoiding medications that increase bleeding risk
• Regularly monitoring IgM levels, complete blood counts, and coagulation studies to assess bleeding risk

According to the most recent and highest quality study, the European Myeloma Network recommends the combination of rituximab with chemotherapy as the treatment cornerstone for patients with Waldenström's macroglobulinemia, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease 1. The bleeding tendency typically improves as the underlying Waldenström's macroglobulinemia is controlled and IgM levels decrease.

From the FDA Drug Label

Hematologic: prolonged pancytopenia, marrow hypoplasia, Grade 3-4 prolonged or late-onset neutropenia, hyperviscosity syndrome in Waldenstrom's macroglobulinemia, prolonged hypogammaglobulinemia [see Warnings and Precautions (5. 6)].

The association between Waldenström's macroglobulinemia and bleeding is not directly stated in the drug label. However, hyperviscosity syndrome is mentioned as a potential adverse reaction in patients with Waldenström's macroglobulinemia. Hyperviscosity syndrome can increase the risk of bleeding due to the increased viscosity of blood. Key points:

• Hyperviscosity syndrome is a potential adverse reaction in Waldenström's macroglobulinemia.
• Bleeding risk may be increased due to hyperviscosity syndrome. 2

From the Research

Association between Waldenström's Macroglobulinemia and Bleeding

• Waldenström's macroglobulinemia (WM) is a rare, incurable, low-grade, B cell lymphoma that can manifest with bleeding symptoms among others 3.
• The causes of the bleeding phenotype in WM are complex and involve several intersecting mechanisms, including acquired von Willebrand factor syndrome, hyperviscosity, abnormal hematopoiesis, cryoglobulinemia, and amyloidosis 3.
• Evidence of defects in platelet function is lacking in the literature, but factors impacting platelet function and coagulation pathways may contribute to bleeding in WM patients 3.
• Clinical features of WM include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy, which can increase the risk of bleeding 4, 5, 6, 7.
• Treatment of WM, including chemo-immunotherapy and Bruton's tyrosine kinase inhibitors, can also carry attendant bleeding risks 3.

Bleeding Risk Factors in WM

• Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics that are predictive of outcomes in WM patients, including bleeding risk 5, 6, 7.
• Patients with disease-related hemoglobin <10 g/L, platelets <100 × 10(9)/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or transformed disease should be considered for therapy to reduce bleeding risk 4.
• The use of anticoagulant or antiplatelet drugs in WM patients requires careful consideration of the bleeding risk, particularly in older patients with comorbidities 3.

Diagnostic and Management Considerations

• Understanding the pathophysiological mechanisms behind bleeding in WM is important to better stratify patients according to their bleeding risk and enhance confidence in clinical decisions regarding treatment management 3.
• Current and emerging diagnostic tools can aid in the evaluation and management of bleeding in WM patients, including the assessment of platelet function and coagulation pathways 3.
• Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression, and secondary malignancies, and planning for future autologous stem cell transplantation 4.