In rare cases, Tirofiban, a small nonpeptide ligand-mimetic glycoprotein (GP) 2b/3a inhibitor, can lead to thrombocytopenia, according to a review article published in the Annals of Medicine. The reaction is thought to be due to an immune-mediated response leading to drug-induced immune thrombocytopenia (ITP).
Evidence from several studies points to the reaction being driven by the binding of drug-dependent antibodies (DDAbs) to GP 2b/3a receptors on platelets after they have undergone conformational changes induced by tirofiban. The attached DDAbs are then detected by macrophages and cleared from circulation, resulting in thrombocytopenia.
Read more about ITP pathophysiology
Several risk factors for tirofiban-induced ITP were identified from the literature review, including having chronic kidney disease, congestive heart failure, being 65 years of age or older, diabetes mellitus, and having white blood cell counts greater than or equal to 12 x 109/L.
In the literature, the majority of cases occurred within the first 24 hours after administration of tirofiban, but some cases took up to 10 days to manifest, and close monitoring of platelet levels was recommended at 6, 12, and 24 hours after admission. Many of the cases resulted in bleeding symptoms and sometimes life-threatening symptoms, including alveolar and gastrointestinal hemorrhages.
The review found 3 major treatment strategies for treating tirofiban-induced ITP, including interventions to minimize bleeding risk, supportive care, and drug regimen modifications. Discontinuation of treatment should be considered if platelet counts drop below 100 x 109/L as the risk of bleeding increases below this point. Platelet counts generally normalized between 1 and 6 days (mean, 2.1 days) after discontinuation, but recovery could be slower in patients with renal or hepatic insufficiency.
For patients with active bleeding and severe thrombocytopenia (platelets < 20 x 109/L), platelet transfusions are recommended; however, the efficacy may be reduced while tirofiban is still in circulation. Supplementation of fibrinogen with fresh frozen plasma or cryoprecipitate may also be considered in cases of persistent major bleeding.
Corticosteroids and intravenous immunoglobulin can be given as supportive care to increase platelet levels and speed up recovery.
“Since the drug-dependent antibodies may persist for years, patients should avoid using the drug in the future and should be cautious when using other GP 2b-3a inhibitors,” the authors cautioned.
Tirofiban is indicated for the treatment of nonST-segment elevation acute coronary syndrome.
Reference
Wang J, Zou D. Tirofiban-induced thrombocytopenia. Ann Med. Published online July 13, 2023. doi:10.1080/07853890.2023.2233425
