Infliximab-induced thrombocytopenia in a patient with ulcerative colitis

Abstract

Dear Editor:We report here a case of drug-induced thrombocytopenia associated to infliximab in a patient with ulcerative colitis (UC). A 30-year-old male was first diagnosed with ulcerative colitis of pancolitis type in 2007. He had been treated with 5-aminosalicylate and azathioprine. Two months prior to hospitalization, he had abdominal pain, diarrhea, and bloody stool, and got worse. He was subsequently started with oral prednisone 0.5 mg/kg daily and cytapheresis. However, the symptoms did not improve, and the sigmoidoscopy study revealed loss of a vascular pattern, erosions, and ulcerations in the rectum and sigmoid colon. Then, he was admitted to our hospital.A blood test on admission revealed a white blood cell (WBC) count of 15,390/μL (Neut; 90.5 %), hemoglobin 12.6 mg/dL, platelet count of 223×10 9 /L, and serum CRP of 1.02 mg/dL. The disease activity index showed a Lichtiger's clinical activity index of 12 points, indicating high activity of UC. After confirming the absence of tuberculosis and hepatitis B virus infection by serological test and computer tomography, infliximab was administered at a dose of 5 mg/kg. Five days after administration of infliximab treatment, diarrhea and bloody stool disappeared, and his general condition was much improved. However, the routine blood test at the tenth day after infliximab infusion showed a platelet count of 23×10 9 / L, WBC count of 6,260/μL, and hemoglobin count of 8.5 mg/ dL. His fibrinogen, fibrin, fibrin-degradation products, PT, and aPTT were all within normal limits. We suspected infliximab-induced thrombocytopenia. We stopped infliximab treatment and transfused ten units of blood platelet to him. Despite the discontinuation of the infliximab treatment, thrombocyte counts remained low (20-60 × 10 9 /L) for 7 weeks. Prednisone was tapered in 5 mg per week. We evaluated the serum infliximab concentration, speculating that residual infliximab may be the cause of thrombocytopenia. The serum infliximab concentration at 6 weeks after infusion was 0.68 μg/mL. The patient was discharged 2 months later, and he recovered from thrombocytopenia (122×10 9 /L) at the 12th week after infliximab infusion.We present a case of a patient who developed thrombocytopenia due to the first administration of infliximab. Thrombocytopenia lasted for 7 weeks after infliximab infusion. The concentration of infliximab at 6 weeks after administration of infliximab fell below the effective blood concentration (above 1 μg/mL) but kept a little lower level (0.68 μg/mL). Therefore, we strongly suspect that the cause of continuous thrombocytopenia was residual infliximab.Two cases of rheumatoid arthritis patients who developed leukopenia and thrombocytopenia induced by an anti-tumor necrosis factor-α (TNF-α) drug were reported; a case showed an improved thrombocytopenia after withdrawal of infliximab; in another case, there was a recovery of leukopenia and a persistence of thrombocytopenia for 2 months [1]. A study of 130 patients having rheumatoid arthritis on anti-TNF-α therapy showed a...

Pathophysiology and Diagnosis of Drug-Induced Immune Thrombocytopenia

“…A moderately low platelet count is relatively common upon exposure to these agents, but more severe thrombocytopenia has also been reported in a few patients. The drugs involved are efalizumab (anti-CD11a) [63,64], adalimumab [65] and infliximab (anti-TNF, tumor necrosis factor) [28,29], bevacizumab (anti-VEGF) [27,66], rituximab (anti-CD20) [30,31], natalizumab (anti-α 4 β 1 -integrin) [32], and immune checkpoint antibodies to program cell death receptor-1 (PD-1) or cytoxic T-lymphocyte antigen 4 (CTLA-4), such as nivolumab, pembrolizumab, or ipilimumab [33,67]. Although the clinical evolution in most cases suggests that antibodies are involved in platelet destruction, their presence has never been firmly demonstrated.…”

“…Platelet count usually falls within a few days of treatment, sometimes with bleedings, and recover rapidly after the drug withdrawal. Moreover, recurrence of thrombocytopenia is inconstant after re-exposure [28,64].…”