If an emergency surgical intervention or invasive procedure is required, it may in some cases be possible to postpone it until at least 12?h (and ideally 24?h) after the last NOAC dose intake to reduce the risk of bleeding complications [11]. However, there are situations such as life-threatening bleeding ML 161 or urgent interventions when discontinuation of the NOAC treatment is insufficient to address the clinical need, particularly among patients with renal impairment [14]. approved specific reversal agent. activated partial thromboplastin time, creatinine clearance, C-reactive protein, dilute thrombin time, deep vein thrombosis, estimated glomerular filtration rate, hemoglobin concentration, intensive care unit, modified rankin scale, National Institutes of Health Stroke Scale, non-valvular atrial fibrillation, platelet, recombinant tissue plasminogen activator, thrombin time Case 1: an 83-year-old man with excessive bleeding after emergency cardiac surgery [9] An 83-year-old man presented with ascending aortic aneurysm complicated by acute aortic syndrome [type A intramural hematoma (IMH)], confirmed by computer tomography. The condition, in the absence of a surgical intervention, is associated with a poor prognosis (morality rate of 1% per hour during the first 48?h). Transthoracic echocardiography identified moderate aortic insufficiency and acute exacerbation of chronic kidney disease [estimated glomerular filtration rate (eGFR) of 19 mL/min/1.73m2]. The patient had non-valvular atrial fibrillation (NVAF) for which he was on dabigatran (110?mg b.i.d., last intake on the day of admission). Furthermore, he had stage 3 chronic kidney disease, arterial hypertension, and a history of right hemispheric ischemic stroke, peripheral arterial disease, peptic ulcer disease of duodenum and basal cell carcinoma resection (face and chest). Emergency cardiac surgery with cardiopulmonary bypass (CPB) and deep hypothermia with temporary circulatory arrest was performed. The dabigatran level [dilute thrombin time (dTT)] before surgery was 209?ng/mL. Anticoagulation for the intervention was achieved by administration of heparin (500?IU/kg) before the onset of CPB and monitored using the activated clotting time with a target of 400?s during CPB. The supracoronary ascending aortic and hemiarch replacement procedure was successfully performed. The aortic cross-clamping time was 64?min, cerebral perfusion time was 34?min and total CPB time was 195?min. At the end of CPB, anticoagulation was reversed by protamine to obtain a normal activated clotting time. Tranexamic acid was administered in two doses [20?mg/kg intravenously (i.v.) after sternotomy and 20?mg/kg i.v. after the end of CPB). At the end of CPB, the hemoglobin level was 8.4?g/dL. A total of 12 units of platelet concentrate and 3 units of fresh frozen plasma were administered in the operating room. Due to excessive perioperative bleeding, idarucizumab (5?g i.v.) was administered following CPB cessation. After surgery, the patient was transferred to the intensive care unit (ICU) for postoperative ventilation and extubated after 17?h. The level of dabigatran after idarucizumab administration was below 32?ng/mL. Three units of packed red ML 161 blood cells (PRBC) were transfused in the intensive care unit (ICU). Total postoperative drainage was 470 mL. During the postoperative course, the patient required diuretic treatment and intensive pulmonary rehabilitation. The postoperative course was complicated with pneumonia which resolved after antibiotics. Anticoagulation with warfarin was reinitiated, and on postoperative day 8 the patient was discharged to a local hospital for further management. On postoperative day 30, the follow-up was uneventful. Case 2: a 93-year-old woman requiring urgent treatment of a periprosthetic femoral hip fracture After a fall, a 93-year-old woman was admitted to hospital with a periprosthetic femoral hip fracture and bleeding caused by the accident. The patient had previously been prescribed dabigatran 110?mg b.i.d. for NVAF and had an implanted pacemaker. The laboratory results at admission included an activated partial thromboplastin time (aPTT) of 46?s and a thrombin time (TT) of 225?s. In the next 24?h, TT (170?s) did not fall to acceptable values for surgery and the patient was transfused 2 units of PRBC due to blood loss into her thigh. Taking into consideration a national recommendation to perform surgery of fractures next to the hip within 48?h, the interdisciplinary decision was made to perform revision arthroplasty the next day and to administer the first vial of idarucizumab (2.5?g i.v.) before the procedure, which resulted in a TT of 17?s. Surgery was initiated, and during the operation the patient received the second vial of ML 161 idarucizumab (2.5?g i.v.) as well as 1?g of tranexamic acid, 2?g of fibrinogen concentrate, 15?g of desmopressin, 5 units of PRBC (including autologous cell salvaged blood) and 2 units Mouse monoclonal antibody to UCHL1 / PGP9.5. The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiolprotease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene isspecifically expressed in the neurons and in cells of the diffuse neuroendocrine system.Mutations in this gene may be associated with Parkinson disease of solvent/detergent plasma. The patient remained under postoperative monitoring in the intensive/intermediate care unit for 4 days without any complication. On postoperative days 1 and 2, TT rose again to 129?s and 131?s, respectively, after.
