Can multiple myeloma (MM) cause bleeding?

Can Multiple Myeloma Cause Bleeding?

Yes, multiple myeloma (MM) can cause bleeding complications, with approximately 7% of newly diagnosed patients experiencing bleeding manifestations including mucosal bleeding, gastrointestinal bleeding, skin manifestations, and intracranial hemorrhage. 1, 2

Mechanisms of Bleeding in Multiple Myeloma

Multiple myeloma can lead to bleeding through several mechanisms:

1. Coagulation abnormalities:

   • Production of thrombin-inhibiting substances that can interfere with normal clotting 2
   • Interference with fibrinopeptide A release from fibrinogen 2

2. Hematological effects:

   • Thrombocytopenia due to bone marrow infiltration
   • Platelet dysfunction
   • Hyperviscosity syndrome

Bleeding Risk vs. Thrombotic Risk

Interestingly, MM presents a complex hemostatic picture:

• Paradoxical hypercoagulable state: MM patients have an inherently high risk of venous thromboembolism (VTE) 1, 3, 4

  • Elevated thrombin generation compared to healthy controls 4
  • High-risk MM patients show even greater elevation of plasma thrombin generation 4

• Bleeding risk factors in MM patients include:

  • Advanced age 5
  • Higher comorbidity index 5
  • History of previous bleeding 5
  • Hypertension 5
  • Renal disease 5

Management Considerations

1. Anti-myeloma therapy: Effective treatment of the underlying MM is the cornerstone of managing bleeding complications 1, 2

   • Case reports show improvement in coagulation abnormalities after treatment with regimens like daratumumab, lenalidomide, and dexamethasone 2

2. Supportive care:

   • Platelet transfusions
   • Fresh frozen plasma
   • Cryoprecipitate as needed 1

3. Thromboprophylaxis considerations:

   • Despite the bleeding risk, anticoagulant prophylaxis does not significantly increase bleeding risk in MM patients 1, 5, 6
   • Recent research (2024) shows anticoagulant use within 6 months was associated with reduced VTE risk (OR 0.45) 6
   • Bleeding occurred in only 1.4% of MM patients on thromboprophylaxis during a median follow-up of 1.3 years 5

Clinical Pitfalls and Caveats

• Underutilization of thromboprophylaxis: Despite recommendations, thromboprophylaxis is often underutilized (only 6.6% in one study) due to concerns about bleeding risk 5, 6

• Immunomodulatory drugs (IMiDs) like thalidomide and lenalidomide increase thrombotic risk, requiring careful consideration of thromboprophylaxis 1, 6

• Monitoring requirements: MM patients should be closely monitored for both bleeding and thrombotic complications, especially when starting new treatment regimens

• Statistical considerations: Traditional statistical methods may overestimate thromboembolism risk in MM patients due to the competing risk of death 3