What workup is required before starting azathioprine in a patient with Fabry disease?

Workup Before Starting Azathioprine

Before initiating azathioprine, you must check TPMT activity (or genotype), complete blood count, liver function tests, and consider hepatitis B/C and varicella zoster virus serology. 1, 2, 3

Essential Baseline Laboratory Tests

Mandatory Tests

• TPMT activity or genotyping: This is critical to identify patients at high risk for severe myelotoxicity and guide initial dosing. Patients with absent TPMT activity should not receive azathioprine. 1, 2, 3
• Complete blood count (CBC) with platelet count: Establishes baseline hematologic parameters before therapy. 1, 2, 3
• Liver function tests (LFTs): Including transaminases (ALT, AST) and bilirubin to assess baseline hepatic function. 1, 2
• Renal function: Urea and electrolytes/creatinine to establish baseline kidney function. 1

Strongly Recommended Infectious Disease Screening

• Hepatitis B and C serology: Screen all patients prior to immunosuppression, particularly important given the hepatotoxic potential of azathioprine. 1, 2
• Varicella zoster virus (VZV) serology: Check in patients without clear history of chickenpox, as VZV exposure during immunosuppression can be life-threatening. 1, 2
• HIV serology: Consider in high-risk populations before initiating immunosuppression. 1

Critical Pre-Treatment Contraindication Assessment

Absolute Contraindications to Identify 4

• Hypersensitivity to azathioprine or 6-mercaptopurine
• Very low or absent TPMT activity (homozygous deficient)
• Severe active infections
• Severely impaired hepatic or bone marrow function
• History of pancreatitis

Important Drug Interaction Review 4, 3

• Allopurinol or febuxostat: Requires 65-75% azathioprine dose reduction or avoidance due to severe myelosuppression risk
• Aminosalicylates (sulfasalazine, mesalazine, olsalazine): Inhibit TPMT and increase toxicity risk
• Ribavirin: Can cause severe pancytopenia
• ACE inhibitors: May induce severe leukopenia
• Warfarin: Azathioprine may impair anticoagulant effect

Patient Counseling Requirements

Warning Signs Requiring Urgent Medical Attention 1, 4

Patients must be instructed to seek immediate care for:

• High fever or severe flu-like illness (possible bone marrow suppression or infection)
• Unexplained bruising or bleeding (thrombocytopenia)
• New-onset jaundice (hepatotoxicity)
• Sudden severe abdominal pain (possible pancreatitis)

Documentation

• Provide written patient information leaflet and document this in medical notes 1
• Discuss licensed vs. unlicensed indications as appropriate 1
• Ensure shared decision-making with adequate time for patient consideration 1

Special Considerations for Fabry Disease Context

While the provided Fabry disease guidelines 1 do not specifically address azathioprine use, the standard azathioprine workup applies. Fabry patients may have pre-existing renal, cardiac, and hepatic involvement, making baseline organ function assessment particularly important. 1 Given that Fabry patients often have proteinuria and declining renal function, careful baseline documentation of renal parameters is essential before adding an immunosuppressant. 1

Common Pitfalls to Avoid

• Do not skip TPMT testing: Approximately 0.3% of the population has absent TPMT activity and will develop life-threatening myelosuppression on standard doses. 1, 2
• Do not overlook drug interactions: Failure to identify concurrent allopurinol use is a common and potentially fatal error. 4, 3
• Do not assume recent blood transfusion patients can have accurate TPMT phenotyping: Transfused red blood cells will interfere with enzyme activity testing; genotyping may be preferred in this scenario. 3
• Do not forget hepatitis screening: Reactivation of hepatitis B during immunosuppression can be catastrophic. 2