Dabigatran Use Associated with Hemopericardium and Hemothorax

Concurrent spontaneous hemopericardium and hemothorax due to anticoagulant use are extremely rare in clinical practice. Dabigatran is an oral direct thrombin inhibitor approved to prevent stroke or thromboembolic episodes in patients with nonvalvular atrial fibrillation. We report the case of a 73-year-old man who received dabigatran therapy (150 mg twice a day) for 3 months and developed massive spontaneous hemothorax and hemopericardium associated with fever. Emergency chest computed tomography scan established higher-density pericardial effusion (22HU) and left pleural effusion of heterogeneous density (5–15 HU) which could be hemorrhagic content while the heart ultrasound finding confirmed pericardial effusion 7–9 mm thick, without affecting hemodynamics. Almost 1100 mL of blood was drained by ultrasoundguided thoracentesis. After excluding other possible causes, diagnostic withdrawal was performed for dabigatran and no further pleural or pericardium effusion developed after dabigatran was discontinued. Therefore, practitioners could be aware of hemothorax as well as hemopericardium as a potential complication of dabigatran therapy.

Severe haematuria of lower urinary tract origin with low dose dabigatran use in three Indian elderly patients: unresolved issues in the safety of novel oral anticoagulants

Dabigatran is a newer oral direct thrombin inhibitor approved by the United States Food and Drug Administration and the European Medicines Agency (EMA). The proper dosage of the drug, the potential for adverse drug reactions and the nature of bleeds with use of this drug as with other novel oral anticoagulants (NOACs), in the elderly population are still areas of uncertainty. Despite the existence of a specific antibody, idarucizumab which is an antidote to dabigatran toxicity, management of dabigatran-induced bleeds is an undefined area especially in resource constrained settings. We report severe haematuria with dabigatran in three elderly Indian patients at the lowest recommended therapeutic dose and explore these grey zones in dabigatran therapy.

Coagulation System

Anticoagulation is increasingly prevalent in the general population and poses a significant risk of increased bleeding in patients needing urgent or emergent surgical procedures. There are two main classes of direct or anticoagulants: direct thrombin inhibitors and factor Xa inhibitors. Management of these patients requires assessment of bleeding risk, possible reversal of anticoagulation, and subsequent management after surgery to prevent postoperative complications associated with either bleeding or clot formation (due to cessation of anticoagulants). This chapter covers the proper assessment and management of patients on oral direct thrombin inhibitor or oral Factor Xa inhibitor therapies.

Two-Year Carcinogenicity Studies With the Oral Direct Thrombin Inhibitor Ximelagatran in the Rat and the Mouse

The results of 18 months mouse and 24 months rat carcinogenicity studies with the oral direct thrombin inhibitor ximelagatran are presented. In the mouse, gavage doses of ximelagatran up to 180 μmol/kg per d produced no neoplastic changes in any of the tissues examined. In the rat, gavage doses up to 240 μmol/kg per d produced multiple macroscopically detectable nodules in the pancreas, which are seen to be focal/multifocal acinar cell hyperplasia and focal/multifocal acinar cell adenoma upon histological evaluation. There were no other treatment-related effects on tumor incidence or distribution in the rat. The studies show a clear species difference in pancreatic effects between the rat and the mouse to long-term treatment with ximelagatran.