What is the recommended workup for a patient with Fabry disease prior to initiating azathioprine therapy?

Workup for Azathioprine in Fabry Disease Patients

Essential Pre-Treatment Laboratory Testing

Before initiating azathioprine in any patient, including those with Fabry disease, you must check TPMT activity or genotyping to identify patients at high risk for severe myelotoxicity—approximately 0.3% of the population has absent TPMT activity and will develop life-threatening myelosuppression on standard doses. 1, 2

Mandatory Baseline Hematologic Assessment

• Complete blood count (CBC) with differential and platelet count is essential to establish baseline parameters before therapy 1, 2
• TPMT genotyping or phenotyping must be performed, though it cannot substitute for ongoing CBC monitoring 2
• Consider NUDT15 genotyping in patients with severe myelosuppression, as deficiency increases risk for life-threatening toxicity 2
• Note that accurate TPMT phenotyping is not possible in patients who received recent blood transfusions 2

Critical Organ Function Assessment

• Liver function tests (ALT, AST, bilirubin) to evaluate baseline hepatic function 1, 2
• Renal function (creatinine, urea, electrolytes) to assess baseline kidney function 1
• This is particularly crucial in Fabry patients who have pre-existing renal involvement and progressive nephropathy 3, 1, 4

Infectious Disease Screening

• Hepatitis B and C serology must be checked before immunosuppression—reactivation of hepatitis B during immunosuppression can be catastrophic 1
• Varicella zoster virus (VZV) serology in patients without clear chickenpox history, as VZV exposure during immunosuppression can be life-threatening 1
• HIV serology should be considered in high-risk populations 1

Fabry-Specific Baseline Considerations

Since Fabry patients have multiorgan involvement that progresses silently, additional baseline documentation is essential before adding an immunosuppressant:

• Urinary protein including creatinine-to-albumin ratio and creatinine clearance to establish renal function baseline 3
• Echocardiography and electrocardiography to document cardiac status 3
• Blood pressure measurement as hypertension control is essential in Fabry disease 3, 5
• These parameters should already be monitored annually in Fabry patients, but must be documented immediately before azathioprine initiation 3

Absolute Contraindications to Screen For

• Hypersensitivity to azathioprine or 6-mercaptopurine 1
• Severe active infections 1
• Severely impaired hepatic or bone marrow function 1
• History of pancreatitis 1

Critical Drug Interaction Assessment

Failure to identify concurrent allopurinol use is a common and potentially fatal error. 1

• Allopurinol or febuxostat: Requires 65-75% azathioprine dose reduction or complete avoidance due to severe myelosuppression risk 1, 2
• ACE inhibitors: May induce severe leukopenia—particularly relevant as ACE inhibitors are recommended for Fabry patients with proteinuria 5, 1, 2
• Ribavirin: Can cause severe pancytopenia 1, 2
• Warfarin: Azathioprine may impair anticoagulant effect 1, 2
• Aminosalicylates (sulfasalazine, mesalazine, olsalazine): Inhibit TPMT enzyme; use with caution 2

Patient Counseling Requirements

• Provide written patient information leaflet and document this in medical notes 1
• Instruct patients to seek immediate care for:
  • High fever or severe flu-like illness 1
  • Unexplained bruising or bleeding 1
  • New-onset jaundice 1
  • Sudden severe abdominal pain 1

Common Pitfalls to Avoid

• Missing TPMT testing: 0.3% of patients have absent activity and will develop life-threatening toxicity 1
• Overlooking allopurinol co-prescription: This interaction can be fatal 1
• Inadequate hepatitis screening: Reactivation during immunosuppression is catastrophic 1
• Ignoring pre-existing renal impairment: Fabry patients commonly have progressive nephropathy that may be silent by routine measures 4
• Failing to document baseline organ function: Essential in Fabry patients who have multiorgan involvement 3, 1