Case Report Series of Left Atrial Thrombus Formation in Patients on Dabigatran Therapy

Abstract

Dabigatran etexilate mesylate, a direct thrombin inhibitor, has been approved in the United States as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. The authors report 2 cases of development of large left atrial thrombi and unfortunate occurrence of thromboembolic events in patients with chronic atrial fibrillation, despite these patients being compliant with recommended dabigatran therapy. The authors postulate that certain unique pharmacologic characteristics of the drug may be disadvantageous toward providing a therapeutic level of anticoagulation in all patients and may provide an explanation of occurrence of these thrombotic events, namely, (1) a competitive, reversible, and incomplete inhibition of only one coagulation factor (thrombin), as opposed to warfarin that leads to noncompetitive inhibition of multiple coagulation factors, (2) a short half-life (12-17 hours) and linear pharmacodynamics related to drug levels that conceivably causes an hourly variation of the level of anticoagulation, (3) a much lower incidence of supratherapeutic anticoagulation ("overshoot") with dabigatran as compared with warfarin, and (4) a reported increase in the coagulation factors that follows long-term use of dabigatran. Also, the absence of routine monitoring to test the therapeutic efficacy of the drug prevents diagnosis of cases where anticoagulation remains subtherapeutic. These factors could explain occurrence of the thrombotic and thromboembolic events in our cases.

Thrombus Formation in Left Atrium on Dabigatran Therapy

“…It has also been used in patients with atrial fibrillation who had documented left atrial thrombus, proving its role in resolution of thrombus [ 4 , 5 ]. However, left atrial thrombus formation on dabigatran therapy as in our case has been reported in 3 other cases in the literature till date [ 6 , 7 ]. Sharma et al [ 6 ] recently reported two cases of left atrial thrombus formation on dabigatran therapy for chronic atrial fibrillation.…”

“…However, left atrial thrombus formation on dabigatran therapy as in our case has been reported in 3 other cases in the literature till date [ 6 , 7 ]. Sharma et al [ 6 ] recently reported two cases of left atrial thrombus formation on dabigatran therapy for chronic atrial fibrillation. One of the patients had lung cancer which could have contributed to additional risk of thrombosis, while the other patient was similar to our case.…”

Successful thrombolysis for acute ischaemic stroke after reversal of dabigatran etexilate with idarucizumab

“…However, this therapeutic advantage of dabigatran is not observed in the treatment of left atrial appendage thrombus, with many reports showing variable responses from increasing the clot size to complete clot resolution 19–22…”

Left Atrial Appendage Thrombus Formation in a Patient on Dabigatran Therapy Associated With ABCB1 and CES-1 Genetic Defect

“…Luis et al ( 2013 ) firstly reported the images which demonstrated the documented case of thrombosis in atrial fibrillation with coexistent valvular heart disease after 4 months anticoagulation with dabigatran. Sharma et al ( 2014 ) report 2 cases of development of large left atrial thrombus in spite of the continuous treatment with dabigatran. Shah et al ( 2015 ) reported another patient with thrombus formation in the left atrium.…”