LAUSR

The introduction of direct oral anticoagulants (DOACs) has changed the perspective about the patient’s needs in clinical practice. A complete understanding of their optimal management has yet to be achieved especially when dealing with critical patients. Recently, a case has raised relevant questions about the correct management of patients presenting with severe bleeding during DOAC treatment. Starting from the learning points obtained from the case, we propose a possible algorithm to improve the care of patients presenting with severe bleeding during DOAC treatment. Before discussing, we report the case briefly. A 65-year-old woman who was taking rivaroxaban 20 mg/day and acetylsalicylic acid 75 mg/day for ischaemic cardiomyopathy with persistent atrial fibrillation (AF) (CHA2DS2 VASC = 7), and recent history of ischemia in the upper limb, presented to the emergency department (ED) because of a syncope after 2 days of melaena. At admission, the patient (who suffered from hypertension) presented with 90/60 mmHg of arterial pressure, pale skin, and an hemoglobin level of 7.4 g/dL. (Her baseline level was 11.8 g/dL.) Crystalloids were administered immediately, and the patient received 50 IU/kg (total 3250 IU) of four-factor prothrombin complex concentrate (4F-PCC) in the preparation for digestive endoscopy. Blood transfusions were followed (2 units of red blood cells in 3 h) to achieve hemodynamic stability. At the time of 4F-PCC infusion, 23 h had passed from the last rivaroxaban 20 mg ingestion, and the patient’s creatinine clearance estimated by Cockroft–Gault was 78 ml/min. A rivaroxaban plasma level was measured at presentation, but was not considered, since 4F-PCC had been administered before the laboratory reported the value (22.2 ng/ml, measured with chromogenic anti-Xa assay). The patient was transferred to our step-down unit where, after 48 h from ED admission, she suffered from a cortical/subcortical cerebral stroke, even though acetylsalicylic acid 75 mg had already been reintroduced. Therefore, enoxaparin sodium 4000 IU s.c. b.i.d. was introduced. However, in the following 2 days, the patient presented a peripheral ischemia in a foot and subsequently a transitory ischemic attack. Only after 5 days from 4F-PCC administration and introduction of lowdosage apixaban (2.5 mg b.i.d.), we did achieve stabilization. 4F-PCC infusion was appropriate when strictly considering the severity of the bleeding and the number of hours from last DOAC ingestion, since recent consensus statements indicate 24 h as the cutoff time in a patient with normal renal and hepatic functions [1–3]. However, drug plasma levels were actually below the safety concentration (see below), and 4F-PCC infusion had likely caused the subsequent ischaemic events in a patient at high thromboembolic risk. Moreover, during the patient’s stay, esophagogastroduodenoscopy (EGD) showed multiple gastric angiodysplasias, which suggested further investigation leading to hereditary hemorrhagic telangiectasia (HHT) diagnosis, with three out of four Curacao criteria (epistaxis, telangiectases, visceral lesions, and family history), and a first-degree relative presenting two out of four criteria. HHT may have primarily * Davide Donelli [email protected]