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Many anticoagulants are indicated as prophylaxis and treatment for conditions that may lead to thromboembolisms or atrial fibrillation. Among those, apixaban, a reversible direct inhibitor of factor Xa, is one of the most popular. Apixaban is known to cause a variety of side effects; however, for this paper, the focus is on hypersensitivity reactions. Although several cases will be referenced from the literature, we present a case with a history of a dermatological disease before the use of a direct oral anticoagulant. A 74-year-old female patient with a history of pemphigus vulgaris and a diagnosis of pulmonary embolism and right distal vein thrombosis managed with apixaban presented with a pruritic coalescent erythematous dermatitis throughout her torso, back, and lower extremities three days post-apixaban treatment. In accordance with her physical examination, the apixaban regimen was withdrawn, and oral dabigatran, a direct thrombin inhibitor, was initiated. At the patient's five-day follow-up, clinical improvement was noted. Through clinical diagnosis, it is believed that this dermatitis was a reaction to the apixaban treatment course., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nadella et al.)

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report two cases of COVID-19-associated atrial fibrillation (AF) in two elderly females and a case of atrial flutter (AFlutter) in a middle-aged male patient. We believe this case series will contribute to the literature on new-onset AF and AFlutter in patients with acute COVID-19 infection. This case series illustrates various case scenarios of patients developing cardiac arrhythmia with acute COVID-19 infection without any prior history or other explicable cause of AF/AFlutter. The exact mechanism behind COVID-19 infection leading to AF or AFlutter is still unknown. Of the three patients reported, two converted to sinus rhythm following medical management, and one did not convert to sinus rhythm despite medical treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dolkar et al.)

Apixaban is known to prolong international normalized ratio (INR) per some observational and in vitro studies. In patients with elevated INR secondary to apixaban use, median INR of 1.4-1.7 has been reported. Extreme elevation in INR is rare with apixaban. In patients with end-stage renal disease (ESRD) on hemodialysis (HD), there are no labeled indications for apixaban use; however, there are some pharmacokinetic data supporting its use in such patients. We present a case of a 68-year-old Hispanic man with ESRD who presented to the emergency room (ER) with INR of 27.42. INR testing was done as a part of routine workup in rehabilitation facility. Medication list was reviewed and included apixaban 2.5 mg twice daily which was recently started for postoperative thromboprophylaxis. INR testing was repeated for confirmation in ER and was reported as >18.5 and prothrombin time >200 seconds. His liver function tests were stable as compared to baseline testing five days ago with normal bilirubin, low normal transaminases, and mild hypoalbuminemia. The patient didn't have any active bleeding. An elevation of INR to >20 with apixaban is a rare event. No other factors including patient characteristics, laboratory results, co-existing conditions, or other medications except the direct oral anticoagulant (DOAC) were found to be responsible for elevated INR. Liver cirrhosis or vitamin K deficiency as cause for INR elevation was ruled out as the baseline INR was normal prior to starting apixaban, liver function tests were stable and INR normalized again shortly after discontinuing the medication. Plasma concentration of DOACs has been found to be correlating with the INR according to a pharmacokinetic study which potentially means that the high INR likely was secondary to high serum concentration of apixaban in this patient. However, INR monitoring is not recommended for monitoring anticoagulant activity of DOACs. As of note, renal clearance accounts for 27% of apixaban clearance. Pharmacokinetic studies have concluded that half dose apixaban, i.e., 2.5 mg twice daily in patients on hemodialysis (dose used in this case) results in drug exposure similar to that of the standard dose of 5 mg twice daily in patients with preserved renal function. Future studies are necessary to address questions about safety of DOACs in patients with ESRD, further elucidate the clinical significance of such high INR values associated with DOACs, and establish appropriate management guidelines. Andexanet alfa has since been approved for apixaban reversal in patients with life-threatening bleeding; however, would not be indicated in such cases when there is no evidence of bleeding., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kahlon et al.)

According to the ARISTOTLE trial, apixaban was superior to warfarin because it was associated with fewer strokes, systemic embolism, and bleeding. Hemopericardium was one of the major bleeding events reported in this trial. However, the percentage of patients that developed hemopericardium was not stated in the trial results. We present a case of hemopericardium in an 80-year-old man admitted for dyspnea, cough, and lower extremity edema. He was recently diagnosed with paroxysmal atrial fibrillation and started on apixaban for stroke prevention. Prior to admission, he was taking metoprolol succinate and amiodarone for atrial fibrillation. His symptoms resolved after undergoing successful pericardiocentesis. Although hemopericardium is a rare side effect associated with the use of non-vitamin K oral anticoagulants (NOACs), we suspect that a drug-drug interaction between apixaban and amiodarone (via the cytochrome p450 system and p-glycoprotein efflux pumps), the patient's advanced age, and borderline creatinine are possible risk factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Olagunju et al.)

Spontaneous spinal epidural hematoma (SSEH) is a rare clinical entity that can result in severe neurological deficit and warrants emergent neurosurgical evaluation and management. The exact etiology of this entity remains unknown, but certain risk factors exist, including the use of anticoagulant medications. There are few published reports of the association of SSEH with direct factor Xa inhibitors. We aimed to present 2 cases of SSEH in patients on chronic apixaban therapy. To the best of our knowledge, there is only 1 other report of SSEH in the setting of apixaban therapy. A comparison between the cases suggests the importance of rapid recognition and management of SSEH in order to achieve favorable neurological outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Mezzacappa et al.)

Atraumatic adrenal hemorrhage is a rare injury, often due to the disruption of normal hemostasis secondary to sepsis, autoimmune disease, or chronic anticoagulation. We present a case of recurrent adrenal hemorrhage in a patient with antiphospholipid syndrome previously maintained on warfarin for deep vein thrombosis and pulmonary embolism prophylaxis who worsened shortly after transition to apixaban therapy. Initial left-sided adrenal hemorrhage occurred four weeks after beginning apixaban, followed by the development of retinal hemorrhage and later right-sided adrenal hemorrhage. This is, to date, the first reported case of adrenal hemorrhage in a patient receiving chronic anticoagulation with apixaban., Competing Interests: The authors have declared that no competing interests exist.