Can autoimmune hepatitis cause elevated white and red blood cell counts?

Can Autoimmune Hepatitis Cause Elevated White and Red Blood Cell Counts?

Autoimmune hepatitis (AIH) does not typically cause elevated white or red blood cell counts; in fact, the opposite is more common—AIH patients often present with cytopenias (low blood counts) due to hypersplenism from cirrhosis or as a side effect of immunosuppressive treatment. 1

Hematological Abnormalities in AIH

Expected Blood Count Patterns

• Cytopenias are the typical finding in AIH patients, particularly those with advanced disease and cirrhosis with portal hypertension leading to hypersplenism 1
• White blood cell counts below 2.5 × 10⁹/L and platelet counts below 50 × 10⁹/L are common enough that they represent contraindications to starting azathioprine therapy 1
• Moderate leucopenia is common in cirrhosis and does not necessarily increase the risk of azathioprine-related marrow depression, though it complicates monitoring 1

Autoimmune Hemolytic Anemia Association

• AIH can be associated with autoimmune hemolytic anemia (AIHA), though this is rare 2
• When AIHA occurs with AIH, it causes hemolysis and anemia (low red blood cell counts), not elevated red blood cell counts 2
• The association between AIH and AIHA is rarely reported, but both are autoimmune in nature 2
• Measurement of red blood cell-associated IgG is recommended in AIH cases with anemia, even when direct antiglobulin test is negative 2

Red Blood Cell Distribution Width (RDW)

• Elevated RDW (red blood cell distribution width) is associated with more severe liver inflammation in AIH patients 3
• RDW levels correlate positively with grades of liver inflammation (r=0.356, P < 0.001) 3
• This represents increased variation in red blood cell size, not an elevated red blood cell count 3

Treatment-Related Hematological Effects

Immunosuppressive Therapy Impact

• Azathioprine causes myelosuppression, resulting in reduced granulocyte, platelet, and red cell counts 1
• These reductions are usually mild and well-tolerated unless pre-existing hematological problems or hypersplenism exist 1
• Blood counts return to normal after therapy cessation 1
• Regular monitoring of blood counts is mandatory: weekly for 4 weeks, then 1-3 monthly thereafter during treatment 1

TPMT Deficiency Considerations

• Homozygous TPMT (thiopurine methyltransferase) deficiency (approximately 1 in 300 people) leads to accumulation of active metabolites and serious marrow toxicity 1
• TPMT measurement should be considered to exclude homozygous deficiency, particularly in patients with pre-existing leucopenia 1

When to Suspect Alternative Diagnoses

Elevated Blood Counts Should Prompt Investigation For:

• Concurrent hematological malignancies or myeloproliferative disorders (not caused by AIH itself)
• Systemic lupus erythematosus (SLE) overlap: 2.2-2.8% of AIH patients have concurrent SLE, which can present with various hematological abnormalities 1, 4
• Inflammatory bowel disease overlap: occurs in 2-11.4% of AIH patients and may have different hematological profiles 1
• Infection or inflammatory response unrelated to the AIH itself

Important Caveats

• If a patient with AIH presents with elevated white blood cell counts, consider acute infection, steroid-induced leukocytosis, or an unrelated hematological condition 1
• If elevated red blood cell counts are present, this is not a feature of AIH and warrants separate investigation for polycythemia vera or secondary erythrocytosis
• Thrombocytopenia and hemolytic anemia are the autoimmune hematological complications associated with AIH, not thrombocytosis or polycythemia 2

Clinical Monitoring Recommendations

• Baseline complete blood count should be obtained before starting immunosuppressive therapy 1
• Weekly monitoring for 4 weeks, then 1-3 monthly monitoring of blood counts during treatment 1
• Any significant cytopenias may necessitate dose reduction or alternative immunosuppressive agents like mycophenolate 1
• Consider TPMT testing in patients with pre-existing leucopenia before starting azathioprine 1