Can Azathioprine and Low-Dose Steroids Affect Blood Markers?
Yes, both azathioprine 150 mg daily and prednisone 5 mg daily can significantly affect multiple blood markers, including liver function tests, complete blood count parameters, and inflammatory markers like CRP and RDW.
Effects on Liver Function Tests
Azathioprine causes hepatotoxicity in a dose-dependent manner, with elevation of serum alkaline phosphatase, bilirubin, and transaminases being well-documented complications. 1
- Hepatotoxicity occurs in less than 1% of patients with inflammatory conditions but is more common (up to 6 months post-treatment) in transplant recipients 1
- Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is mandatory for early detection of hepatotoxicity 2, 1
- Azathioprine can cause severe hepatic complications including cirrhosis and nodular regenerative hyperplasia, even after years of therapy 3, 4, 5
- The dose of azathioprine should be reduced or stopped if liver enzymes exceed three times the upper limit of normal 2
Effects on Complete Blood Count
Myelosuppression is the most clinically significant hematologic effect, occurring in over 50% of transplant patients and 28% of rheumatoid arthritis patients to some degree. 1
Leukopenia
- Leukopenia (WBC <3.0 × 10⁹/L) occurs in 3.8% of patients, with severe leukopenia (WBC <2.0 × 10⁹/L) in approximately 1.2% 6
- Azathioprine should be stopped or reduced by 50% immediately if WBC falls below 4,000/mm³ 2
- Myelotoxicity can develop at any time during treatment, from 2 weeks to 11 years after initiation 6
Thrombocytopenia
- Thrombocytopenia (platelets <100,000 × 10⁶/L) occurs in 2% of patients 6
- Immediate withdrawal and hematology consultation are required when platelets drop below 50 × 10⁹/L 7
Macrocytosis and Anemia
- Macrocytic anemia is a common finding that can be used to assess patient compliance 8
- Anemia occurs but is less common than leukopenia 8
Lymphopenia
- Lymphopenia occurs in 57% of patients on long-term azathioprine maintenance therapy 2
- Azathioprine discontinuation or dose reduction is recommended when lymphocyte count falls below 0.5 × 10⁹/L 7
Effects on Inflammatory Markers
Low-dose corticosteroids (5 mg prednisone daily) suppress inflammatory markers including CRP, which is a desired therapeutic effect in autoimmune conditions. 2
- Normalization of inflammatory markers including CRP is an important endpoint of successful immunosuppressive therapy 9
- The combination of azathioprine and low-dose prednisone is specifically designed to maintain disease quiescence while minimizing side effects 2
Red Cell Distribution Width (RDW)
- RDW may be elevated due to azathioprine-induced macrocytosis 8
- The development of macrocytic changes reflects the drug's effect on DNA synthesis in rapidly dividing cells 1
Monitoring Requirements After 8 Months of Therapy
At 8 months of continuous therapy, patients should be on a reduced monitoring schedule but remain under surveillance. 2
- Complete blood count and liver function tests should be performed at minimum every 3 months 2, 8
- More frequent monitoring is required if any abnormalities develop or if doses are adjusted 2
- Weekly monitoring should resume if the azathioprine dose is increased 2
Critical Clinical Considerations
Patients with TPMT or NUDT15 deficiency are at dramatically increased risk for severe, life-threatening myelosuppression. 1
- Approximately 0.3% of European/African ancestry patients have absent TPMT activity and are at risk for fatal pancytopenia 1, 10
- 10% have intermediate TPMT activity requiring dose reduction 2, 1
- Among East Asian patients, 2% have two loss-of-function NUDT15 alleles and 21% have one 1
- In patients with severe myelosuppression, evaluation for TPMT and NUDT15 deficiency should be considered 1
Steroid Effects on Blood Markers
Prednisone 5 mg daily represents a low maintenance dose that typically causes minimal direct hematologic effects but suppresses inflammatory markers. 2