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Background Apixaban, a non‐vitamin K oral anticoagulant (NOAC), was approved in Japan in 2012 for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and effectiveness of apixaban in clinical practice have not yet been elucidated thoroughly among Japanese NVAF patients. Methods A postmarketing surveillance study was conducted to determine the safety and effectiveness of apixaban. Patients were followed‐up for 104 weeks. Outcome events included adverse drug reactions (ADRs), hemorrhages, and thromboembolic events (ischemic stroke, systemic embolism [SE], and transient ischemic attack [TIA]). Results Among 6306 NVAF patients in the safety analysis set (age, 74.5 ± 10.1 years; women, 41.1%; and CHADS 2 score, 2.0 ± 1.4), 3600 patients (57.1%) received the standard dose (5 mg twice daily) and 2694 (42.7%) received a reduced dose (2.5 mg twice daily) of apixaban. ADRs occurred in 604 patients (9.58%), with the most common being epistaxis (0.86%), subcutaneous hemorrhage (0.67%), and hematuria (0.57%). Incidence rate of any hemorrhages and major hemorrhage was 5.52% per year and 2.36% per year, respectively. Incidence rate of ischemic stroke/SE/TIA was 1.00% per year among 6286 patients in the effectiveness analysis set. Among three subgroups (3106 apixaban initiators, 2038 patients switched from warfarin, and 1118 patients switched from other NOACs), incidence rates of major hemorrhage (P = 0.221 for trend) and ischemic stroke/SE/TIA (P = 0.686 for trend) were comparable. Conclusions No new safety signals of apixaban were identified in Japanese NVAF patients. Safety and effectiveness of apixaban were consistent with those in the ARISTOTLE study.

Objective To report the use of a vascular closure device (VCD) to provide rapid arterial hemostasis following percutaneous femoral arterial catheterization and diagnostic angiography in a thrombocytopenic and coagulopathic dog. Case Summary A 6-year-old female spayed Kai Ken Tora dog presented after vehicular trauma. The dog was diagnosed with traumatic pneumothorax, degloving wounds of the right antebrachium, subcutaneous hemorrhage within the axillary tissues of the left thoracic limb, and anemia and thrombocytopenia secondary to acute hemorrhage. Treatment included therapeutic thoracocentesis and open wound management of the right thoracic limb as well as packed RBC and fresh frozen plasma transfusions. Diagnostic angiography of the left brachial artery was performed via percutaneous femoral arterial access to investigate the source of a persistent axillary hematoma. The arterial access site was closed using an extraluminal VCD and hemostasis was immediate with normal femoral arterial blood flow documented by Doppler ultrasound. New or Unique Information Provided This report describes use of a VCD for arterial closure following percutaneous access in a dog with impaired hemostasis; to the authors’ knowledge, this is the first clinical report of a VCD used in a veterinary species.

Aim: Hemorrhage is an important complication of heparin-thromboprophylaxis after surgery. We attempted to clarify the incidence rate of prolonged activated partial thromboplastin time (APTT), representative of hemorrhagic tendency, in Japanese women who received thromboprophylaxis with unfractionated subcutaneous heparin administration after cesarean section (CS). We also determined factors which affected postoperative APTT. Methods: We studied 280 women who were administered thromboprophylaxis with unfractionated subcutaneous heparin 5000 IU two times per day after CS. Postoperative APTT under heparin was measured and the incidence of its prolongation was determined. Preoperative APTT, blood loss during surgery, postoperative hematocrit, postoperative serum total protein level, and postpartum body weight were measured, and their correlation with postoperative APTT was determined. Results: Preoperative and postoperative APTT values were 28.3 (26.7–30.3) and 33.8 (31.0–37.5) seconds for median (interquartile range), respectively. Overall, 7.1% of patients showed ≥45 s postoperative APTT. Two patients (0.7%) showed ≥60 s APTT, one of whom suffered subcutaneous hemorrhage around the abdominal incision with complete healing. There were no other hemorrhagic complications. Preoperative APTT positively, and postpartum body weight inversely, correlated with postoperative APTT. The amount of blood loss, postoperative hematocrit, and postoperative serum total protein level did not correlate with postoperative APTT. No discernible deep vein thrombosis or pulmonary embolism occurred. Conclusion: Although 7.1% of women under heparin-thromboprophylaxis showed a prolonged APTT that was 150% of the preoperative APTT, serious side effects were not observed. Subcutaneous administration of unfractionated heparin, if checking APTT prolongation 1 day after surgery, may be safe method of thromboprophylaxis after CS.

The incidence of acute massive hemorrhage in hemodialysis (HD) patients is thought to be higher than in healthy individuals, and a large, expanding subcutaneous hematoma can result in necrosis of the overlying skin. We evaluated the efficacy of intra-arterial treatment for acute massive subcutaneous hemorrhage in HD patients. Seven HD patients with subcutaneous hemorrhage following minor blunt trauma were treated using superselective transarterial embolization, between July 2005 and October 2012. After examining the site of the hemorrhage using contrast-enhanced computed tomography (CT), embolizations were performed using microcoils, gelatin sponges, or N-butyl cyanoacrylate. Hematoma evacuation or skin grafting was performed as needed. Four men and three women with a mean age of 70 years (range, 63-82 years) comprised the study population. Sites of bleeding were as follows: lower leg (N = 3), upper leg (N = 1), buttock (N = 1), precordia (N = 1), and forearm (N = 1). Blood transfusions were administered to five cases. All patients were successfully salvaged using transarterial embolization. Six patients underwent hematoma evacuation after transarterial embolization, and two patients underwent split-thickness skin grafting for skin necrosis. We established a treatment strategy for HD patients with acute subcutaneous hemorrhage. Immediate confirmation of the site and the degree of bleeding with contrast-enhanced CT and early treatment using the transarterial embolization and as needed, hematoma evacuation are effective for preventing skin necrosis in HD patients with acute subcutaneous hemorrhage.

Adult bullfrogs, Rana catesbeiana, were exposed to water supersaturated with atmospheric air. Exposure to a differential pressure (δP) of 250 mm Hg [total gas pressure (TGP) = 132.9% of atmospheric pressure] resulted in a 40% mortality within one day owing to the accumulation of gas in the vascular system. Exposure to a AP of 128 mm Hg (TGP = 116.8%) for four days had no effect on bullfrog mortality, but produced subcutaneous gas bubbles in the webbing and on body surfaces, followed by hyperemia (tissue engorged with blood through blood vessel dilation), and petechial (small subcutaneous hemorrhage spot) and ecchymotic (large subcutaneous hemorrhage spot) hemorrhaging. Owing to accumulation of gas under the skin, these frogs typically floated and were unable to remain submerged. These clinical signs are similar to those commonly reported for “redleg” disease syndrome in bullfrogs. When held at a δP of 67 mm Hg (TGP = 108.8%) for 27 days, no clinical signs of gas bubble trauma were observed.

The teratogenic effects of L-azetidine-2-carboxylic acid (LACA) were evaluated in hamsters. Single or multiple intraperitoneal injections of LACA were given on gestational days 7–12. Fetal weights were significantly reduced in several LACA-treated groups as compared to controls. The frequency of external anomalies was significantly higher than controls in only two LACA-treated groups: 7.2% in 600 mg/kg on day 12 and 9.6% in 200 mg/kg/day on days 10–12. Subcutaneous hemorrhage and cleft palate were the most frequently occurring externally visible defects. Skeletal anomalies such as retarded ossification, asynchronous vertebral ossification and shortening of bones were found in a high percentage of LACA-treated fetuses. The major teratological effect of LACA appeared to be the retardation of skeletal development.