OBJECTIVE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls.
METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province.
RESULTS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group.
CONCLUSIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.

Hemothorax is a rare and potentially fatal condition characterized by pleural effusion containing over 50% of the patient\'s hematocrit. A massive hemothorax involves blood loss exceeding 1.5 L. Common causes include chest trauma, invasive thoracic procedures, anticoagulant medications, vascular anomalies, malignancies, and hematologic abnormalities. Spontaneous hemothorax may be seen in conjunction with pulmonary infarction and spontaneous pneumothorax. Anticoagulation is a key therapeutic strategy for certain thromboembolic events, such as pulmonary embolism. Historically, these events were treated with vitamin K antagonists (VKAs), which have demonstrated variable plasma concentrations and an increased risk of hemorrhage. With the advent of direct oral anticoagulants (DOACs), treatment has become as effective as VKAs while significantly reducing the risk of hemorrhage. However, some researchers have speculated that hemorrhagic complications in certain cases could be worse with DOACs than with VKAs. In the case presented here, we identified a genuine association between the use of rivaroxaban and spontaneous hemothorax following the initiation of treatment for pulmonary embolism.

A 76-year-old Japanese man underwent right upper lung lobectomy for lung cancer. He had a medical history of atrial fibrillation and myocardial infarction, and was treated with medications including apixaban (5 mg twice daily). His postoperative course was uneventful, and he left the hospital on the ninth day postoperatively. Apixaban was restarted on postoperative day (POD) 10. On POD18, he was evaluated as an outpatient. He complained of fatigue, and his hemoglobin level decreased from 13.5 to 8.5 mg/dL. Chest plain radiography showed massive fluid in the right thoracic cavity. His condition was thought to be a postoperative bleeding complication due to apixaban; thus, we stopped apixaban and performed red blood cell transfusion and thoracic drainage. Postoperative hemorrhage associated with apixaban use is rare.