Blood Tests Before Starting Rituximab
All patients must undergo hepatitis B virus (HBV) screening with HBsAg, anti-HBc, and anti-HBs before initiating rituximab, along with complete blood counts (CBC) including differential and platelets. 1
Mandatory Pre-Treatment Laboratory Testing
Hepatitis B Virus Screening (Universal - All Patients)
- HBsAg (hepatitis B surface antigen) - identifies active chronic infection 1, 2
- Anti-HBc (hepatitis B core antibody) - detects prior or occult infection 1, 2
- Anti-HBs (hepatitis B surface antibody) - assesses immunity status 2
This triple HBV screening is non-negotiable because rituximab carries the highest risk of HBV reactivation among all immunosuppressive agents, which can result in fulminant hepatitis and death. 2 The risk is so significant that prophylactic antiviral therapy is strongly recommended (not just monitoring) for all rituximab patients who are anti-HBc positive, regardless of HBsAg status. 2
Complete Blood Count with Differential
- CBC including platelets and differential white cell count must be obtained before the first dose 1
- This establishes baseline values for monitoring cytopenias during treatment 1
- Rituximab can cause late-onset neutropenia and thrombocytopenia 2, 3
Liver Function Tests
- Transaminases (ALT/AST) should be checked at baseline 2
- These are essential for monitoring potential HBV reactivation during therapy 2
Renal Function Tests
- Serum creatinine and estimated GFR are recommended before starting rituximab 2
- This is particularly important in patients with ANCA-associated vasculitis or other kidney involvement 2
Additional Testing Based on Clinical Context
Immunoglobulin Levels
- Baseline IgG level should be measured, as low IgG (<3 g/L) predicts greater risk of secondary immunodeficiency with rituximab 2
- Monitor IgG every 6 months during rituximab therapy 2
Tuberculosis Screening
- TB screening (interferon-gamma release assay or tuberculin skin test) is recommended unless already performed before other immunosuppressive therapy without subsequent TB exposure 2
- Chest X-ray should be obtained if not recently performed 2
HIV Testing
- HIV testing is recommended for patients with HIV risk factors 2
Management Algorithm for HBV Test Results
If HBsAg Positive (Active Chronic HBV)
- Start potent antiviral therapy (entecavir, tenofovir, or tenofovir alafenamide - NOT lamivudine) before rituximab 2
- Continue antiviral for at least 18 months after stopping rituximab 2
- Consult hepatology before proceeding 2
If HBsAg Negative but Anti-HBc Positive (Prior/Occult HBV)
- Obtain baseline HBV DNA to rule out occult active infection 2
- Start prophylactic antiviral therapy (entecavir or tenofovir preferred) - this is strongly recommended, not optional 2
- Continue antiviral for at least 18 months after stopping rituximab 2
- Monitor HBsAg, ALT, and HBV DNA every 1-3 months during therapy 2
If All HBV Tests Negative
- Proceed with rituximab without antiviral prophylaxis 2
- Consider HBV vaccination if anti-HBs is also negative 2
Critical Pitfalls to Avoid
Do not start rituximab without completing HBV screening - studies show only 23-79% of patients receive appropriate testing, leading to preventable cases of fatal hepatitis. 4, 5
Do not rely on monitoring alone for anti-HBc positive patients - the ACR strongly recommends prophylactic antiviral therapy over monitoring for all rituximab patients who are anti-HBc positive, because HBsAg seroreversion is consistently associated with hepatitis flare. 2
Do not use lamivudine for HBV prophylaxis - it has high resistance rates; use entecavir, tenofovir, or tenofovir alafenamide instead. 2
Do not delay rituximab for patients with high serum IgM (>4000 mg/dL) in Waldenström's macroglobulinemia - instead, perform prophylactic plasmapheresis first to prevent hyperviscosity syndrome from IgM flare. 2
Screen for non-melanoma skin cancer in at-risk patients before starting therapy. 2