|Year : 2021 | Volume
| Issue : 2 | Page : 74-77
Eptifibatide-induced acute profound thrombocytopenia in a patient with left main artery plaque rupture complicated by cardiogenic shock and gastrointestinal bleeding
Savvy Nandal MBBS 1, William Van Gaal MD, MSc, MBBS, FCSANZ, FESC 2, Francis A Ponnuthurai MBBCh, FRACP, FCSANZ, DDU 1
1 Department of Cardiology, The Northern Hospital, Melbourne, VIC, Australia
2 Department of Cardiology, The Northern Hospital; Department of Cardiology, The University of Melbourne, Melbourne, VIC, Australia
|Date of Submission||09-Nov-2020|
|Date of Decision||31-Jan-2021|
|Date of Acceptance||07-May-2021|
|Date of Web Publication||22-Jun-2021|
Dr. Savvy Nandal
The Northern Hospital, 185 Cooper Street, Epping, Melbourne, VIC
Source of Support: None, Conflict of Interest: None
Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen and adhesion proteins such as fibronectin, vitronectin, and von Willebrand factor to form cross bridges with adjacent platelets. There are two other GP IIb/IIIa inhibitors, namely abciximab and tirofiban, available for clinical use. Profound thrombocytopenia is an uncommon but clinically important complication of GP IIb/IIIa inhibitors. This case discusses a 64-year-old male patient who developed profound thrombocytopenia within 4 h of first administration of eptifibatide. This report adds a case of eptifibatide-induced thrombocytopenia complicated by gastrointestinal bleeding to the medical literature. It highlights the need for complex decision-making regarding cessation of antiplatelet therapy in patients with recent percutaneous coronary intervention and the lack of robust evidence for the benefit of GP IIb/IIIa inhibitors in the ticagrelor era when compared to clopidogrel and aspirin.
Keywords: Eptifibatide, myocardial infarction, thrombocytopenia
|How to cite this article:|
Nandal S, Van Gaal W, Ponnuthurai FA. Eptifibatide-induced acute profound thrombocytopenia in a patient with left main artery plaque rupture complicated by cardiogenic shock and gastrointestinal bleeding. J Clin Prev Cardiol 2021;10:74-7
|How to cite this URL:|
Nandal S, Van Gaal W, Ponnuthurai FA. Eptifibatide-induced acute profound thrombocytopenia in a patient with left main artery plaque rupture complicated by cardiogenic shock and gastrointestinal bleeding. J Clin Prev Cardiol [serial online] 2021 [cited 2022 Jul 6];10:74-7. Available from: https://www.jcpconline.org/text.asp?2021/10/2/74/319047
| Introduction|| |
Eptifibatide inhibits platelet aggregation by competitive antagonism of the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, preventing fibrinogen and adhesion proteins such as fibronectin, vitronectin, and von Willebrand factor to form cross bridges with adjacent platelets. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner. There are two other GP IIb/IIIa inhibitors, namely abciximab and tirofiban, available for clinical use.
Concomitant administration of eptifibatide has been shown to improve outcomes in clinical studies in patients undergoing percutaneous coronary intervention (PCI). Profound thrombocytopenia is an uncommon but clinically important complication of GP IIb/IIIa inhibitors. In clinical trials, 0.7%–2% of patients developed thrombocytopenia after initial exposure and up to 4.6% in patients after re-exposure.
This case discusses a 64-year-old male patient who developed profound thrombocytopenia within 4 h of first administration of eptifibatide, complicated by gastrointestinal bleeding and cardiogenic shock.
| Case Report|| |
A 64-year-old male with no previous history of cardiovascular disease presented with acute retrosternal chest pain with associated nausea, vomiting, and diaphoresis. There was no previous history of blood dyscrasia, thrombocytopenia, or any cardiovascular risk factors. In addition, he had no prior history of hospitalization where he may have received heparin or eptifibatide.
Initial electrocardiogram with ambulance showed diffuse ST elevation in V1–6 and I, II, and aVL [Figure 1], therefore, he was diagnosed with anterolateral ST-elevation myocardial infarction. This was complicated by ventricular fibrillation cardiac arrest requiring 1x direct cardioversion with return of spontaneous circulation during transit to a PCI capable hospital. Upon arrival to a tertiary center, he was given aspirin 300 mg, ticagrelor 180 mg, and intravenous (IV) heparin 5000 units.
|Figure 1: Electrocardiogram showing diffuse ST elevation in V1–6 and I, II, and aVL|
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Emergent coronary angiography showed a ruptured plaque in the mid left main stem artery extending into the ostial left anterior descending (LAD) artery with subtotal occlusion of the proximal LAD secondary to thrombus, TIMI 1 flow in the LAD [Figure 2]. The left circumflex artery was the dominant vessel with ostial 40% stenosis, proximal 30% stenosis, and mid 20% stenosis. The right coronary artery was small and nondominant. Two IV eptifibatide boluses of 6.8 ml each were administered; 8 min apart prior to stent deployment for thrombus management, however, infusion therapy was not commenced. A 4.0 mm × 26 mm Resolute Onyx drug-eluting stent was deployed at 14 atm from the proximal left main into proximal LAD with pre and post dilatation resulting in TIMI III flow [Figure 3].
|Figure 2: Coronary angiogram demonstrating left main plaque rupture with subtotal occlusion of the left anterior descending artery due to thrombus|
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|Figure 3: Coronary angiogram demonstrating successful percutaneous coronary intervention to left main-left anterior descending artery with flow restoration|
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During the PCI procedure, the patient developed cardiogenic shock and large hematemesis with worsening hemodynamic instability, requiring inotropic support, intubation for airway protection, and transfer to the intensive care unit (ICU).
Initial blood testing at presentation showed a platelet count of 249 × 109/L. Repeat bloods which were performed in ICU approximately 4 h post eptifibatide initiation, the patient was noted to have developed profound thrombocytopenia with platelet count reduction by >90% to 6 × 109/L. All other complete blood count parameters remained stable.
All antiplatelet or anticoagulant products including aspirin and ticagrelor were withheld for 24 h due to the significant risk of spontaneous bleeding such as intracranial bleeding which outweighed the risk of in-stent thrombosis. Other causes of acute thrombocytopenia including heparin-induced thrombocytopenia (HIT) using the 4T score, disseminated intravascular coagulopathy, and pseudothrombocytopenia were excluded based on temporal relationship and blood testing. The patient was given 1 unit of platelets with recovery of his platelet count, as shown in [Figure 4]. Proton-pump inhibitor therapy was administered, however, there was no further hematemesis or melena during recovery in ICU, therefore, immediate upper gastrointestinal endoscopy was delayed until clinical recovery.
Dual antiplatelet therapy (aspirin and ticagrelor) was recommenced the following day, and he continued recovery in the ward without any further complications [Figure 4]. He was discharged home on day 7 of admission on antiplatelets and proton-pump inhibitor therapy. Upper gastrointestinal endoscopy was performed a few months later that showed evidence of duodenitis, which was managed with proton-pump inhibitor therapy.
|Figure 4: Chart presenting the development of profound thrombocytopenia and its recovery|
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| Discussion|| |
GP IIb–IIIa inhibitors are commonly used in patients undergoing PCI, especially among those presenting with acute coronary syndrome. Eptifibatide, one of the three GP IIb/IIIa inhibitors, is a derivative of the naturally occurring rattlesnake venom protein known as barbourin. Eptifibatide has linear, dose-proportional pharmacokinetics, and steady state is achieved within 4–6 h. It is approximately 25% bound to human plasma protein and has elimination half-life in patients undergoing PCI of 2.71 h.
GP IIb/IIIa inhibitors are known to cause thrombocytopenia in 0.7%–2% of patients after initial exposure and up to 4.6% in patients after re-exposure. Clinical trials with eptifibatide include the PURSUIT trial and ESPRIT trial that report acute profound thrombocytopenia at 0.1%–0.2%, which is defined as platelet count <20,000/mm3 usually within 24 h of drug administration.
The pathophysiology of acute profound thrombocytopenia secondary to GP IIb/IIIa inhibitors is speculated by several mechanisms. Preexisting drug antibodies to platelet surface are present in some patients with prior exposure to the drug. However, in patients with no previous exposure, GP IIb/IIIa inhibitors may induce conformational change in their receptor leading to expression of neoepitopes that may be recognized by preformed antibodies. This neoepitope formation creates the possibility of thrombocytopenia arising within a few hours as evident in our case.,
In this case, there was a precipitous platelet count drop leading to upper gastrointestinal bleeding within few hours of eptifibatide infusion. GP IIb/IIIa inhibitor therapies have low rates of life-threatening bleeding and intracranial hemorrhage (<0.2%). However, this risk increases significantly with concomitant development of thrombocytopenia. Therefore, it became imperative in our case to cease all antiplatelet and anticoagulant therapies until the platelet count recovery was established. With resolution of thrombocytopenia, gastrointestinal bleeding self-resolved and the patient underwent gastrointestinal endoscopy at a later stage post clinical recovery.
Other differentials for thrombocytopenia were also considered and thought to be unlikely for the following reasons. Pseudothrombocytopenia and disseminated intravascular coagulopathy were excluded with blood testing including repeat blood count, prothrombin time, activated partial thromboplastin time, and fibrinogen level. HIT types 1 and 2 present days to weeks post heparin exposure usually leading to mild reduction in platelet count. The lack of temporal relationship and history of previous exposure with heparin, the precipitous drop as well as patient's 4T score made HIT unlikely. There have been few case reports of ticagrelor-induced thrombocytopenia since its usage in acute coronary syndrome.,, Two of the case reports describe thrombotic thrombocytopenic purpura occurring months after exposure to ticagrelor with the presence of microangiopathic hemolytic anemia and thrombocytopenia. However, this has not been well characterized in the literature with clinical course and mechanism of action still unclear. In our patient, there was no evidence of hemolytic anemia and re-exposure to ticagrelor did not induce thrombocytopenia again making this drug an unlikely culprit.
This report adds a case of eptifibatide-induced profound thrombocytopenia complicated by gastrointestinal bleeding to the medical literature and highlights the lack of robust evidence for the benefit of GP IIb/IIIa inhibitors in the ticagrelor era when compared to clopidogrel and aspirin., Therefore, judicious usage of GP IIb/IIIa inhibitors is advised with the more potent antiplatelets.
| Conclusion|| |
Early and regular platelet count monitoring is imperative with GP IIb/IIIa inhibitor administration. Profound thrombocytopenia can lead to life-threatening hemorrhagic complications which subsequently needs complex decision-making regarding cessation of antiplatelet therapy in patients with recent PCI. There is limited evidence of the utility of GP IIb/IIIa inhibitors in patients with concomitant ticagrelor.
The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]