Can Sulfasalazine Cause Thrombocytopenia?
Yes, sulfasalazine can cause thrombocytopenia (low platelet count), though it is uncommon, occurring in approximately 1% of patients. This is a recognized hematological adverse effect that requires monitoring with complete blood counts during treatment.
Evidence from FDA Labeling and Guidelines
The FDA drug label explicitly warns that deaths have been reported from blood dyscrasias associated with sulfasalazine, and lists thrombocytopenia among serious hematological complications 1. The label states that "the presence of clinical signs such as sore throat, fever, pallor, purpura, or jaundice may be indications of serious blood disorders" and mandates frequent complete blood counts during therapy 1.
Multiple clinical practice guidelines acknowledge thrombocytopenia as a known adverse effect of sulfasalazine:
- The Toronto Consensus Guidelines for ulcerative colitis list thrombocytopenia among the most common adverse events, occurring in up to 15% of patients taking 5-ASA compounds (which includes sulfasalazine) 2
- The AGA guidelines note that rare but serious hematologic toxicity is possible with sulfasalazine, requiring laboratory monitoring of complete blood counts 2
- The American College of Rheumatology recommends holding or decreasing sulfasalazine immediately when clinically relevant thrombocytopenia occurs alongside other laboratory abnormalities 3
Incidence and Clinical Characteristics
Research studies provide specific incidence data:
- In a large study of 200 patients with inflammatory arthritis, thrombocytopenia occurred in 1% of patients 4
- A prospective study of 300 rheumatoid arthritis patients found thrombocytopenia in one patient (0.3%) at 18 weeks, associated with other hypersensitivity reactions 5
- Another study of 130 patients with inflammatory arthritis observed no cases of thrombocytopenia, though neutropenia occurred in 0.8% 6
The thrombocytopenia is typically idiosyncratic and can occur as part of a hypersensitivity reaction 7. One case report documented severe thrombocytopenia developing during a hypersensitivity reaction with hepatotoxicity and lymphadenopathy 7.
Monitoring Requirements
Complete blood counts should be performed frequently during sulfasalazine therapy 1. Specific monitoring protocols include:
- CBC every 2 weeks for the first 3 months 8
- Monthly CBC for the second 3 months 8
- Every 3 months thereafter 8
- Immediate discontinuation if thrombocytopenia develops, while awaiting confirmatory blood test results 1
Management When Thrombocytopenia Occurs
Discontinue sulfasalazine immediately if thrombocytopenia develops 3, 1. The American College of Rheumatology recommends:
- Holding the medication immediately when clinically relevant thrombocytopenia occurs 3
- Rechecking CBC within 1-2 weeks to confirm improvement 3
- Considering alternative 5-ASA medications such as mesalamine or balsalazide if sulfasalazine must be discontinued for inflammatory bowel disease 9
All hematological complications from sulfasalazine are reversible upon discontinuation 5. In documented cases, platelet counts normalized after stopping the drug 4, 5, 7.
Important Clinical Caveats
While thrombocytopenia is uncommon with sulfasalazine, it is more serious than the more frequent side effects like gastrointestinal symptoms (33%) or CNS reactions (19%) 4. The risk appears similar whether sulfasalazine is used for inflammatory bowel disease or inflammatory arthritis, though reactions may be slightly more frequent in arthritis patients 4.
Patients are at highest risk for serious hypersensitivity reactions, including hematological abnormalities, early in therapy, with most events occurring within the first month of treatment 1. However, thrombocytopenia can occur later in the treatment course, as documented at 18 weeks in one study 5.