From the Guidelines
Leukopenia is a significant side effect of certain medications used to treat inflammatory bowel disease (IBD), particularly azathioprine and 6-mercaptopurine, and requires prompt medical attention to prevent complications and improve quality of life. Patients with IBD who develop leukopenia should immediately contact their gastroenterologist, as this may indicate medication side effects or disease complications 1. The incidence of azathioprine-related leukopenia ranges from 3.2% to 5%, and it can occur suddenly and unpredictably, even with regular blood tests 1.
Causes of Leukopenia in IBD
- Medication-induced bone marrow suppression, particularly with azathioprine and 6-mercaptopurine 1
- Nutritional deficiencies, such as vitamin B12 and folate deficiencies 1
- Extraintestinal manifestations of the disease itself 1
Management of Leukopenia in IBD
- Temporarily reducing or discontinuing the offending medication while monitoring blood counts weekly until they normalize 1
- Administering granulocyte colony-stimulating factor (G-CSF) such as filgrastim at 5 μg/kg subcutaneously daily for severe leukopenia (neutrophil count below 1000/μL) 1
- Considering alternative IBD treatments that are less likely to cause bone marrow suppression, such as biologics like infliximab or adalimumab 1
Importance of Prompt Medical Attention
Patients with leukopenia should be vigilant for signs of infection, such as fever, chills, or unusual fatigue, as their immune system is compromised and infections can progress rapidly 1. Prompt medical attention can help prevent complications, improve quality of life, and reduce morbidity and mortality associated with leukopenia in IBD patients 1.
From the Research
Relationship Between Leukopenia and Inflammatory Bowel Disease (IBD)
- Leukopenia is a well-recognized side effect of thiopurine treatment in patients with IBD, and its association with therapeutic effects has been studied 2.
- A study found that leukopenia during thiopurine maintenance therapy was associated with prolonged remission in patients with IBD and Behcet's disease 2.
- However, another study found that relative leukopenia was not associated with clinical response in patients with IBD on 6-mercaptopurine or azathioprine 3.
Risk Factors for Thiopurine-Induced Leukopenia
- Thiopurine-induced leukopenia is a potentially life-threatening adverse event that complicates the clinical management of IBD patients 4.
- Risk factors for thiopurine-induced leukopenia include TPMT and NUDT15 variants, as well as high 6-thioguanine nucleotides (6-TGN) or 6-methylmercaptopurine (6-MMP) levels 4.
- A study found that patients with certain genetic variants, such as TPMT and NUDT15 R139C, G52A, and 36_37ins/delGGAGTC variant carriers, were at increased risk of thiopurine-induced leukopenia 4.
Management of Leukopenia in IBD Patients
- Assessment of patients with neutropenia should be guided by the severity on presentation, and the duration of leukopenia and the clinical status of the patient should also be considered 5.
- Patients with febrile neutropenia should undergo treatment with antibiotics, and other treatments are aimed at management of the underlying cause of neutropenia 5.
- Early assessment of thiopurine metabolites can identify patients at risk of thiopurine-induced leukopenia in IBD, and validation of the predictive model is needed before implementing in clinical practice 6.