Can Rituxan (rituximab) cause thrombocytopenia?

Rituximab Can Cause Thrombocytopenia

Yes, Rituxan (rituximab) can cause thrombocytopenia as an adverse effect. The FDA drug label specifically lists thrombocytopenia as a known hematologic toxicity, with clinical trials showing an incidence of 2% in patients with non-Hodgkin lymphoma receiving rituximab monotherapy 1.

Incidence and Risk Factors

• Thrombocytopenia occurs more frequently than initially reported in clinical trials, with a cohort study showing a cumulative incidence of 30% within 30 days after rituximab administration, and 20% developing grade 3/4 thrombocytopenia 2
• Risk factors for developing rituximab-induced thrombocytopenia include:
  • Pre-existing low platelet count before rituximab administration 2
  • Treatment within oncology settings compared to autoimmune diseases 2
  • Advanced lymphoma stage, bone marrow infiltration, splenomegaly, and leukemic presentation 3
  • Burkitt lymphoma histology 3

Mechanism and Presentation

• Rituximab-induced thrombocytopenia can present as:
  • Acute severe thrombocytopenia that may occur within 24 hours after administration 4
  • Delayed thrombocytopenia that develops days to weeks after treatment 2
• The mechanism is not fully understood but may involve:
  • Complement activation, as suggested by cases showing low complement levels during thrombocytopenia episodes 5
  • Immune-mediated destruction of platelets 2

Clinical Implications and Management

• Rituximab-induced thrombocytopenia can range from mild to severe and may lead to serious bleeding complications 4
• In some cases, thrombocytopenia can mimic disseminated intravascular coagulation with coagulation abnormalities 4
• Management considerations include:
  • Close monitoring of platelet counts, especially in high-risk patients 4
  • More frequent platelet monitoring is particularly advised in:
    • Patients treated for oncologic indications 2
    • Those with pre-existing low platelet counts 2
    • Patients with bone marrow involvement 3
  • Spontaneous recovery of platelet counts may occur in some cases 5

Rituximab in ITP Treatment

• Paradoxically, rituximab is also used as a treatment for immune thrombocytopenia (ITP) with:
  • Response rates of approximately 60% of patients 6
  • Complete response in about 40% of ITP patients 6
  • Responses typically occurring after 1-8 weeks of treatment 6
  • Duration of response lasting from 1-2 years in responders 6
• For ITP patients, rituximab may be considered:
  • For those with significant ongoing bleeding despite first-line treatments 6
  • As an alternative to splenectomy in chronic ITP 6
  • In combination with corticosteroids in certain cases, though evidence suggests corticosteroids alone may be preferred for initial therapy 6

Monitoring Recommendations

• Platelet counts should be closely monitored during rituximab therapy, particularly in the first 30 days after administration 2
• Other recommended monitoring includes:
  • Complete blood count (CBC) 7
  • Hepatic and renal function tests 7
  • Immunoglobulin levels with long-term use 7

Other Important Safety Considerations

• Besides thrombocytopenia, rituximab can cause other serious adverse effects:
  • Infusion-related reactions (77% with first infusion) 1
  • Infections (31% overall incidence) 1
  • Neutropenia (6%) and lymphopenia (40%) 1
  • Progressive multifocal leukoencephalopathy (rare but serious) 6, 7
  • Hypogammaglobulinemia with long-term use 7

When using rituximab, clinicians should weigh these potential adverse effects against the expected benefits for the specific condition being treated, with particular caution in patients with risk factors for thrombocytopenia.