- Case Report
- Open Access
Eptifibatide-induced acute profound thrombocytopenia: a case report
© Graidis et al.; licensee BioMed Central Ltd. 2014
- Received: 6 June 2013
- Accepted: 7 February 2014
- Published: 25 February 2014
The interactions among cells or among cells and components of the extracellular matrix, is a crucial pathophysiological process involving some molecules collectively known as adhesion molecules (CAMs). Glycoprotein IIb / IIIa receptors are only restricted to blood platelets and they bind fibrinogen and adhesion proteins such as fibronectin, vitronectin, von Willebrand factor to form cross bridges between adjacent platelets. IIb/IIIa receptor antagonists are an object of intense research activity for target therapy worldwide during the last decades. Three GPIIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide, have been approved for clinical use. Profound thrombocytopenia is an uncommon but clinically important complication of glycoprotein IIb/IIIa inhibitors.
This case report discusses a forty-four-year-old male patient with acute coronary syndrome who underwent percutaneous coronary intervention and developed profound thrombocytopenia within 4 hours of first administration of eptifibatide.
This report adds another case of eptifibatide-induced thrombocytopenia to the medical literature and endorses the importance of platelet count monitoring after initiating therapy with this agent.
- IIb/IIIa receptor antagonists
- Cell adhesion molecules
The interactions among cells or among cells and components of the extracellular matrix, is a crucial pathophysiological process involving molecules collectively known as adhesion molecules (CAMs). CAMs are ubiquitously expressed proteins with a key function in physiological maintenance of tissue integrity and an eminent role in various pathological processes such as cardiovascular disorders, atherogenesis, atherosclerotic plaque progression and regulation of the inflammatory response. CAMs such as selectins, integrins, and immunoglobulin superfamily take part in interactions between leukocyte and vascular endothelium (leukocyte rolling, arrest, firm adhesion, migration). Integrins are a family of adhesion molecules performing a major role in such multiple cellular functions including carcinogenesis and metastatic process. The GP IIb/IIIa receptors (fibrinogen or aggregation receptors), belong to the family of integrins which are membrane bound adhesion molecules and are made of two glycoprotein sub-units (a and b). GP IIb/IIIa receptors are only restricted to blood platelets and they bind fibrinogen and adhesion proteins such as fibronectin, vitronectin and von Willebrand factor to form cross bridges between adjacent platelets. IIb/IIIa receptor antagonists are an object of intense research activity for target therapy worldwide during the last decades and they are frequently used during percutaneous coronary intervention (angioplasty with or without intracoronary stent placement) as well as treating acute coronary syndromes, without percutaneous coronary intervention. Three GPIIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide, have been approved for clinical use. All are given by intravenous administration, usually for 12 to 18 h after the patient undergoes angioplasty [1–4]. This case report discusses forty-four-year-old male patient who developed profound thrombocytopenia within 4 hours of first administration of eptifibatide.
While eptifibatide presents significantly improved outcomes in patients undergoing percutaneous coronary intervention and among those presenting with an acute coronary syndrome, a small number of patients given eptifibatide develop acute profound thrombocytopenia (20.000 cells/mm3) within hours of receiving the drug that can increase the risk of serious bleeding with sometimes deleterious effects. The disorder appears to occur less frequently in clinical trials of eptifibatide, the heptapeptide small molecule GPIIb-IIIa inhibitor. In the PURSUIT trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy), which involved patients with non-ST-elevation acute coronary syndrome, acute profound thrombocytopenia occurred in five (0.1%) of 4614 patients treated with eptifibatide and in two of 4603 patients who received placebo . In the ESPRIT trial (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) of non emergent coronary angioplasty with stenting, acute profound thrombocytopenia occurred in two (0.2%) of 1040 patients treated with eptifibatide and in none of the 1024 placebo-treated patients . In the Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT-II) the incidence of thrombocytopenia approximates the 2.8% . Profound thrombocytopenia is an uncommon but clinically important complication of glycoprotein IIb/IIIa inhibitors [13–15].
Drug induced profound thrombocytopenia , a predictor of adverse outcome in patients with acute coronary syndromes, is defined as a decrease in platelet count to below 20,000/mm3 within 24 hours of exposure to the drug and may be associated with the administration of eptifibatide, a glycoprotein antagonist. While the usage of GP IIb/IIIa inhibitors sets an important clinical benefit in the management of ACS, the reporting incidence of acute profound thrombocytopenia induced by eptifibatide is 0.1% to 1% and usually occurs within the first 24 hours. Several pathophysiological mechanisms have been implicated in the explanation of GP IIb/IIIa inhibitors induced acute profound thrombocytopenia. Accumulating evidence has indicated that pre-existing drug dependent antibodies to platelet surfaces are present in patients and that the glycoprotein inhibitors may induce a change in the conformation in the GP IIb/IIIa receptors on the platelet surface, leading to the expression of neoepitopes which are recognized by pre-existing serum antibodies [17, 18]. Another possible mechanism would be the formation of a receptor-antagonist complex by the recognized neoepitopes. In our patient, the physiological platelet count and all other hematological parameters (PT, aPTT, red blood cells, white blood cells) ruled out bone marrow dysfunction, non-immune and immune thrombocytopenia as a cause of thrombocytopenia. Pseudothrombocytopenia was ruled out by manual examination of blood film . There is no evidence in the literature which suggests that the use of tenecteplase is responsible for provoking thrombocytopenia. Not even in the drug monography summary of product characteristics (spc) is mentioned the likelihood of emerging thrombocytopenia after the use of this drug. Additionally, serotonin release assay (HIT panel) came back negative. The fact that the patient continued to be on clopidogrel without recurrence of thrombocytopenia after the normalization of platelet count ruled out clopidogrel as a cause of thrombocytopenia. No history of prior eptifibatide exposure was present and the Naranjo scale score  was 5, indicating a possible relationship between the adverse effect and therapy in this patient. There is an algorithm that has been proposed for the early evaluation and management of this drug related thrombocytopenia. In all patients that receive GP IIb/IIIa inhibitors a complete blood count should be obtained prior to treatment, within 2 hours following the intravenous bolus, in a daily basis after the intervention and again prior to the patient’s discharge [21, 22].
This report adds another case of eptifibatide induced thrombocytopenia to the medical literature and endorses the importance of platelet count monitoring after initiating therapy with this agent.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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