The Poison Review

Hemorrhagic complications associated with dabigatran use. Chen BC et al. Clin Toxicol 2012 Sep 12 [Epub ahead of print]

Abstract

Dabigatran (Pradaxa) is a direct thrombin inhibitor, approved in the U.S. for use to prevent stroke in non-valvular atrial fibrillation. Despite some advantages, dabigatran has two major problems:

1. There is no readily available test that can quantify its anticoagulation effect.
2. There is not antidote that can reliably reverse dabigatran-induced anticoagulation.

This paper presents four cases of bleeding in patients on dabigatran:

1. A 79-year-old man on dabigatran, aspirin, and clopidogrel came to the emergency department with bleeding from the nose and rectum. He was hypotensive (BP 65/47 mmHg). Despite massive transfusion of red blood cells and multiple other interventions, he suffered a bradycardic arrest and could not be resuscitated.
2. A 73-year-old woman on aspirin and dabigatran developed hypotension and cardiac tamponade. She did well after surgical removal of a 350 ml pericardial hematoma.
3. An 86-year-old man on dabigatran came to the emergency department with GI bleeding. Colonoscopy visualized diverticulosis. His vital signs remained stable and he was discharged on warfarin
4. An 80-year-old man on dabigatran tripped and hit his head. Although his neurological exam was unremarkable, CT scan showed a small subdural hematoma. Repeat CT showed no extension of the hematoma, and he was discharged 2 days after admission.

The authors cite a study showing that patients over 75 years of age have an increased risk of bleeding on dabigatran compared with those on warfarin. They conclude that:

. . .concomitant bleeding diathesis, platelet disorders, simultaneous anticoagulation with anti-platelet agents, advanced aged[sic], renal insufficiency, and fall risk increase the likelihood of bleeding and may have contributed to bleeding in these patients.

It is important to realize that dabigatran is eliminated predominantly  by the kidneys, and that the RE-LY trial excluded any patient with a creating clearance less than 30 ml/min. In the elderly, renal insufficiency can be present even with a seemingly normal creatinine level, and may go undetected. Therefore, this population is at particular risk when taking dabigatran.

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