On the day of surgery, baseline blood pressure (BP) was 119/77 mm Hg, heart rate (HR) 67 bpm, respiratory rate 16 per minute, and peripheral oxygen saturation 97% on room air. An interscalene perineural catheter was placed preoperatively for postoperative analgesia (preoperative bolus 20 mL, 0.5% ropivacaine; postoperative infusion 0.2% ropivacaine, 6 mL/h). General endotracheal anesthesia was induced with propofol, fentanyl, and rocuronium and maintained with sevoflurane. TXA (20 mg/kg) was intravenously (IV) administered over 30 minutes after anesthetic induction and positioning. BP was noninvasively monitored by a BP cuff. An arterial line was not placed given the patient’s excellent exercise tolerance, lack of angina symptoms, and recent normal TTE. A low-dose phenylephrine infusion served to maintain BP at baseline values. Because the patient was in the sitting position, cerebral oximetry was used to monitor cerebral perfusion. Normocapnia was maintained during pressure-controlled ventilation. The surgery was uneventful with stable hemodynamics and no ECG abnormalities throughout. Preoperative hemoglobin was 12.5 g/dL, and estimated blood loss was 150 mL. The patient emerged from anesthesia without complication and was monitored in the postanesthesia care unit for approximately 1.5 hours with vital sign assessment every 15 minutes. He did not require any pain medications. On discharge by the anesthesiologist, he was alert and comfortable with excellent pain control from the perineural catheter. Approximately 3 hours later, during routine postoperative evaluation, the orthopedic resident noted an awake, comfortable, and conversant patient. Shortly after, the patient called to the nurse’s station complaining of “feeling sweaty.” A nurse quickly responded and found him diaphoretic but arousable. He complained of dyspnea (respiratory rate, 16 per minute; peripheral oxygen saturation 92% on room air) and was hypotensive (BP, 60/40 mm Hg) and bradycardic (HR, 33 bpm). The emergency medical response team was activated. Atropine (0.5 mg IV) was given for bradycardia with little improvement (HR, 42 bpm). Electrocardiography showed complete heart block and acute inferior wall ST elevation consistent with myocardial infarction. High-flow oxygen therapy was initiated by nonrebreather mask and epinephrine infusion administered for hemodynamic support (0.025 µg/kg/min). Aspirin (325 mg) was given orally. The patient was immediately taken to the cardiac catheterization laboratory. He was alert and hemodynamically stable (114/79 mm Hg) on arrival. He complained of 8/10 chest pain and remained bradycardic with heart block. Epinephrine infusion was continued throughout the 2-hour catheterization procedure without sedation. Coronary angiography showed an acute thrombus at the bifurcation of the circumflex coronary artery and first obtuse marginal artery with total occlusion and restenosis of the bifurcation stent (Figure 1). Successful aspiration thrombectomy of the circumflex and kissing balloon angioplasty of the bifurcation lesion were performed and followed by placement of a DES in the left circumflex artery at the level of the atrioventricular groove. Unfortunately, the occlusion of the first obtuse marginal, suspected to be caused by an acute thrombus, could not be repaired (Figure 2). The patient experienced intermittent hemodynamic instability and increased oxygen requirements over the next 24 hours requiring intensive care unit admission with concern for cardiogenic shock. TTE revealed an ejection fraction of 0.42 with inferior wall hypokinesis. Inotropic support with dobutamine and aggressive diuresis improved the patient’s condition. Aspirin (325 mg) and clopidogrel (75 mg) were administered daily for 2 days and then aspirin reduced to 81 mg daily. He was transitioned to the floor on postoperative day 3 and discharged home on postoperative day 8 on daily clopidogrel (75 mg) and aspirin (81 mg) with instructions to continue DAPT for a minimum of 1 year.
TXA administration combined with DAPT cessation in a cardiac high-risk patient likely contributed to stent rethrombosis. Because TXA inhibits fibrinolysis, its administration may increase the risk of thromboembolic events, such as deep venous thrombosis, pulmonary embolism, or myocardial infarction. While few prior reports have described temporal associations between acute myocardial ischemia and oral TXA administered for menorrhagia or hemoptysis, only 2 prior cases of thromboembolic events after IV TXA administration for orthopedic surgery have been published. In 2016, Gerstein et al8 described left ventricular thrombus formation in a patient with human immunodeficiency virus who received intraoperative TXA (1 g bolus followed by 1 mg/kg/h infusion) for spine surgery. Similar to our case, Garg et al9 described a patient in 2014 who experienced a ST elevation myocardial infarction after hip arthroplasty with intraoperative TXA administration (10 mg/kg IV). Notably, in all these published case reports, the patients did not have any cardiac history. While meta-analyses of TXA administration for arthroplasty have not noted an increased risk for thromboembolic events, patients with elevated risk for thromboembolic events were excluded from many of these trials.4–7 One retrospective review of over 1000 arthroplasty surgeries, which included 240 patients with a risk factor for thromboembolic events who received TXA, did not find an increased rate of thromboembolic events.10 However, large prospective trials are needed to confirm those findings.6,7,10 Our case suggests that the prothrombotic nature of TXA may contribute to life-threatening complications in high-risk patient populations.
Our case differs from prior reports because our patient had several risk factors for coronary artery thrombosis. Coronary DES cause impairment in arterial healing characterized by incomplete reendothelialization which contributes to late stent thrombosis.10 Additional risk factors for late stent thrombosis include overlapping stent placement, excessive stent length, and bifurcation stents.11 Additionally, DAPT was held 7 days before surgery by the patient’s cardiologist without discussion with an anesthesiologist. This management is not consistent with the 2016 American College of Cardiology/American Heart Association guidelines, which recommend continuation of aspirin throughout the perioperative period when possible for patients on DAPT who must discontinue P2Y12 inhibitor therapy.12 These guidelines further state that the patient, surgeon, anesthesiologist, and cardiologist should all be included in the decision-making process. Given that prasugrel was discontinued because of concern for intraoperative bleeding, perioperative continuation of aspirin in this high-risk cardiac patient should have been discussed among care providers. Administration of aspirin on the morning of surgery should have been considered when aspirin cessation was noted. A randomized, double-blind, placebo-controlled trial found that perioperative aspirin reduced the risk of major adverse cardiac events in high-risk patients undergoing noncardiac surgery.13 Although this study was not powered to evaluate bleeding complications, a recent meta-analysis of over 30,000 patients undergoing noncardiac surgery found antiplatelet therapy (aspirin, clopidogrel, or DAPT) to convey minimal bleeding risk.14 The authors concluded that antiplatelet agents were safe to continue when indicated. Although our patient’s most recent stents were placed 5 years prior, DAPT cessation combined with TXA administration likely increased his risk for rethrombosis.
In conclusion, the risk of perioperative hemorrhage must be weighed against the risk of a perioperative ischemic cardiac event. Our patient had a normal preoperative hemoglobin concentration and underwent a surgery with a low likelihood of transfusion. Considering the patient’s history of repeated coronary artery thromboses and a surgical procedure with low bleeding risk, aspirin–and possibly DAPT–should have been continued perioperatively. While it is impossible to define the exact cause of this patient’s coronary stent rethrombosis, the indication for TXA must be based on individual risk assessment. Fortunately, TXA-associated thromboembolic events are uncommon. However, further studies are needed to evaluate the safety profile of TXA in cardiac high-risk patients.
Name: Kathryn H. Bridges, MD.
Contribution: This author helped draft the original case report and perform the literature review.
Name: Sylvia H. Wilson, MD.
Contribution: This author helped edit the case report and search the literature.
This manuscript was handled by: Hans-Joachim Priebe, MD, FRCA, FCAI.
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