Currently, more than six million patients receive long-term antithrombotic therapy in the United States.1 Newer oral anti-coagulants such as dabigatran, rivaroxaban, apixaban act by directly inhibiting factor Xa or thrombin.2 Second and third generation oral antiplatelet medications include clopidrogrel, prasugrel, and ticagrelor, which function as adenosine diphosphate-receptor/P2Y12 antagonists, preventing ADP-induced platelet aggregation and subsequent thrombus formation.2 These medications are used for the management of venous thromboembolism, stroke prevention in atrial fibrillation, treatment of acute coronary syndrome and secondary prevention of cardiovascular disease.3
Here is a case of a patient who presented with sudden onset vision loss who suffered a multi-compartment hemorrhage from over anti-coagulation
The concomitant increase in antithrombotic drugs and patients undergoing long-termantithrombotic therapy poses theoretical challenges for ophthalmologists. While these medications possess a wide therapeutic window and fewer serious adverse events, there are some disadvantages: the lack of reversal agents, inadequate clinical experience and inability to measure the extent of anticoagulation.4 These somewhat uncontrollable characteristics can worsen hemorrhage in ocular conditions such as hemorrhagic posterior vitreous detachment, exudative age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinal vein occlusions or at the time of intraocular surgery.
The literature evaluating the risk of ocular hemorrhage associated with newer anticoagulants is limited. Two cases of spontaneous ocular hemorrhage (choroidal and subretinal) in patients undergoing newer anticoagulation have been previously described.5,6 Additionally, a meta-analysis of 17 randomized controlled trials (RCTs) comparing ocular hemorrhage between newer anticoagulants and vitamin K antagonists found that the rate of substantial ocular hemorrhage, as defined by International Society on Thrombosis and Hemostasis, was quite low (<0.4%).7
However, these studies were designed for FDA approval and were powered for a cardiovascular/thrombotic outcome. Patients with a variety of comorbidities such as uncontrolled hypertension, recent history of myocardial infarction and coronary revascularization typically were excluded from these studies and many times a detailed ophthalmology exam was not performed. Further complicating these matters is that fact that if an ocular hemorrhagic event was observed, it may not have been reported unless it caused visual impairment. Furthermore, in routine clinical practice, patients are prescribed non-standard doses of medications that do not reflect these standard of care studies. Due to these circumstances, the types, as well as their rates, would have been largely unknown and not reported.
In our study published in OSLI-Retina, we found that the prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%) and much higher than the reported literature. The prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature.
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1) Baron TH, Kamath PS, and McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med 2013;368:2113-2124
2) Parekh PJ, Merrell J, Clary M , Brush JE, and Johnson DA. New anticoagulants and antiplatelet agents: a primer for the clinical gastroenterologist. Am J Gastroenterol 2014;109:9-19.
3) Kiire, CA, Mukherjee R, Ruparelia N, Keeling D, Prendergast B, and Norris JH. Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery. Br J Ophthalmol 2014; 98:1320-1324.
4) Bauer KA. Pros and cons of new oral anticoagulants. ASH Education Program Book 2013;1:464-470
5) Kang TS, Lord K, and Kunjukunju N. Spontaneous choroidal hemorrhage in a patient on dabigatran etexilate (Pradaxa). Retin Cases Brief Rep 2014; 8:175-177.
6) Boyce MR, Bradley BE, and Singh A. Recurrent subretinal hemorrhage associated withrivaroxaban anticoagulation. Retin Cases Brief Rep 2015;10:86-88
7) Caldeira D, Canastro M, Barra M, et al. Risk of Substantial Ocular Bleeding With Newer Oral Anticoagulants: Systematic Review and Meta-analysis. JAMA Ophthalmol 2015;133:834-839