Anticoagulants: A Short History, Their Mechanism of Action, Pharmacology, and Indications.

Anticoagulant drugs antagonize coagulation and are used to prevent or cure (recurrent) venous thromboembolism (VTE). Drugs to prevent clotting have been used for more than a century, and, nowadays, physicians possess a broad panel of multiple anticoagulants to meet the individual needs of a patient. Within this review, we aimed to revise the history of the different anticoagulants that are currently prescribed in the clinic. In addition, we compared their pharmacological properties, medical indications, and the difficulties in implementing new anticoagulants in vulnerable patient populations. Since the introduction of unfractionated heparin in the 1930s, major advances in the mechanistic understanding and the medical use of anticoagulants have allowed for significant improvements to treat VTE patients. However, a new generation of anticoagulants is currently being tested in clinical trials, with the goal of further optimizing medical care.

A retrospective review of spontaneous epistaxis outcomes for patients on novel oral anticoagulants compared to antiplatelets and warfarin.

AIMS: The incidence of epistaxis-related admissions amongst elderly patients is rising due to the increasing use of anticoagulants and antiplatelet agents. This retrospective study evaluates the differences in outcomes for patients on warfarin, novel anticoagulants (NOACs) and antiplatelets over two different time periods. METHODOLOGY: Retrospective case-control study with data from patients admitted with epistaxis through the Flinders Medical Centre Emergency Department in the first six months of 2013 and compared to the same period in 2018. The latter coincides with integration of NOACs into Australian prescribing practices. Included participants were ≥50 years with spontaneous epistaxis which coincides with peak incidence in adults. Exclusion criteria were epistaxis due to trauma, intrinsic coagulopathy, or recent post-surgery. Linear regression and binary logistic regression models were the statistical methods used. RESULTS: Data from 85 patients were analysed for length of stay (LOS), readmission rates and method of haemostasis. In 2013, 41 patients were included compared to 44 in 2018, suggesting a 7% increase in admissions rates but this was not statistically significant (p = 0.96). The proportion of patients admitted with epistaxis while taking an anticoagulant or antiplatelet agent increased from 66% in 2013 to 93% in 2018. Thirty six percent of patients in 2018 were taking NOACs, however, LOS was 2 times shorter (mean ratio = 2.08 days, 95% CI: 1.03, 4.19). Seven percent of patients in 2018 had bleeding requiring surgery or interventional radiology, compared to 12% in 2013, but this was not statistically significant. There was no statistically significant difference in readmission rates (p = 0.82) or intervention required (p = 0.74) between the two time periods. CONCLUSIONS: Epistaxis admissions at our institution have increased since the introduction of NOACs. However, most patients can be managed successfully with intranasal packing and cautery alone. NOACs are not associated with increased rated of invasive haemostatic measures and patients have a shorter LOS.

The Impact of Novel Anticoagulants on the Upper Gastrointestinal Tract Mucosa.

Background and objectives: Although treatment with novel oral non-vitamin K antagonist 3anticoagulants (NOACs) is associated with an overall decrease in hemorrhagic complications compared to warfarin, the incidence of gastrointestinal bleeding remains contradictory. Materials and Methods: After the exclusion of patients with pre-existing pathological lesions in the upper gastrointestinal tract (GIT) on esophageal-gastroduodenoscopy (EGD) at entry, a cohort of 80 patients (mean age of 74.8 ± 2.0 years) was randomly divided into four equivalent groups, treated with dabigatran, rivaroxaban, apixaban, or warfarin. Patients were prospectively followed up for three months of treatment, with a focus on anamnestic and endoscopic signs of bleeding. In addition, bleeding risk factors were evaluated. Results: In none of the patients treated with warfarin or NOACs was any serious or clinically significant bleeding recorded within the follow-up period. The incidence of clinical bleeding and endoscopically detected bleeding in the upper GT after three months of treatment was not statistically different among groups (χ2 = 2.8458; p = 0.41608). The presence of Helicobacter pylori (HP) was a risk factor for upper GIT bleeding (p < 0.05), while the use of proton pump inhibitors (PPIs) was a protective factor (p = 0.206; Spearman's correlation coefficient = 0.205). We did not record any post-biopsy continued bleeding. Conclusions: No significant GIT bleeding was found in any of the treatment groups, so we consider it beneficial to perform routine EGD before the initiation of any anticoagulant therapy in patients with an increased risk of upper GIT bleeding. Detection and eradication of HP as well as preventive PPI treatment may mitigate the occurrence of endoscopic bleeding. Endoscopic biopsy during the NOAC treatment is safe.

Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: data from the RE-LY trial.

AIMS: A J-shaped association of cardiovascular events to achieved systolic (SBP) and diastolic (DBP) blood pressure was shown in high-risk patients. This association on oral anticoagulation is unknown. This analysis from RELY assessed the risks of death, stroke or systemic emboli, and bleeding according to mean achieved SBP and DBP in atrial fibrillation on oral anticoagulation. METHODS AND RESULTS: RE-LY patients were followed for 2 years and recruited between 22 December 2005 until 15 December 2007. 18.113 patients were randomized in 951 centres in 54 countries and 18,107 patients with complete blood pressure (BP) data were analysed with a median follow-up of 2.0 years and a complete follow-up in 99.9%. The association between achieved mean SBP and DBP on all-cause death, stroke and systemic embolic events (SSE), major, and any bleeding were explored. On treatment, SBP >140 mmHg and <120 mmHg was associated with all-cause death compared with SBP 120-130 mmHg (reference). For SSE, risk was unchanged at SBP <110 mmHg but increased at 140-160 mmHg (adjusted hazard ratio (HR) 1.81; 1.40-2.33) and SBP ≥160 mmHg (HR 3.35; 2.09-5.36). Major bleeding events were also increased at <110 mmHg and at 110 to <120 mmHg. Interestingly, there was no increased risk of major bleeding at SBP >130 mmHg. Similar patterns were observed for DBP with an increased risk at <70 mmHg (HR 1.55; 1.35-1.78) and >90 mmHg (HR 1.88; 1.43-2.46) for all-cause death compared to 70 to <80 mmHg (reference). Risk for any bleeding was increased at low DBP <70 mmHg (HR 1.46; 1.37-1.56) at DBP 80 to <90 mmHg (HR 1.13; 1.06-1.31) without increased risk at higher achieved DBP. Dabigatran 150 mg twice daily showed an advantage in all patients for all-cause death and SSE and there was an advantage for 110 mg dabigatran twice daily for major bleeding and any bleeding irrespective of SBP or DBP achieved. Similar results were obtained for baseline BP, time-updated BP, and BP as time-varying covariate. CONCLUSION: Low achieved SBP associates with increased risk of death, SSE, and bleeding in patients with atrial fibrillation on oral anticoagulation. Major bleeding events did not occur at higher BP. Low BP might identify high-risk patients not only for death but also for high bleeding risks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov-Identifier: NCT00262600.

The interactions between anticonvulsants and non-vitamin K antagonist oral anticoagulant agents: A systematic review.

Use of non-vitamin K antagonist oral anticoagulants (NOACs), including dabigatran etexilate, rivaroxaban, apixaban, edoxaban or betrixaban provides a safe and convenient alternative to the traditional anticoagulation with vitamin K antagonists or heparin derivatives. Many patients receiving long-term seizure prophylaxis with antiepileptic drugs (AEDs) may require anticoagulation with NOACs. Providers caring for these patients need to be informed about potential interactions between AEDs and NOACs and the relevant clinical consequences. A systematic review of the existing literature was conducted to elucidate current knowledge on the clinically relevant interactions between AEDs and NOACs and highlight areas in which further research is needed. The systematic review protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Ovid MEDLINE, Embase, The Cochrane Library and SciFinder were searched. Of the 630 non-duplicate items identified by the search, 13 met eligibility criteria. These 13 items included 8 case reports, 2 letters to the editor and 3 nonrandomized studies. The majority of pharmacokinetic interactions between NOACs and first generation AEDs occurred via the induction of the hepatic enzyme system and competition for the P-glycoprotein transporter and lead to decreased NOAC plasma levels and consequent thrombotic events. Only one article, a case report, was identified that focused on interactions between the second generation AED and a NOAC. At the present time, the limited evidence suggests that enzyme-inducing or inhibiting AEDs reduce the effectiveness of anticoagulation produced by several NOACs. This information may help providers anticipate possible interactions and guide therapy appropriately.

Routine Repeat Head CT Does Not Change Management in Trauma Patients on Novel Anticoagulants.

INTRODUCTION: Guidelines for imaging anticoagulated patients following a traumatic injury are unclear. Interval CT head (CTH) is often routinely performed after initial negative CTH to assess for delayed intracranial hemorrhage (ICH-d). The rate of ICH-d for patients taking novel oral anticoagulants (NOACs) is unknown. We hypothesized that the incidence of ICH-d in patients on NOACs would be similar, if not lower to that of warfarin, and routine repeat CTH after initial negative would not change management, and thus, may not be indicated. MATERIALS AND METHODS: Anticoagulated patients presenting with blunt trauma to a level I trauma center between 2016 and 2018 were evaluated. Exclusion criteria included: positive initial CTH and those taking nonoral anticoagulation or antiplatelet agents alone (without warfarin or NOAC). Outcomes included: ICH-d, discharge GCS, administration of reversal agents, neurosurgical intervention, readmission, and death. Multivariable regression was performed to evaluate patient factors associated with the development of ICH-d. RESULTS: A total of 332 patients met the inclusion criteria. Patients were divided into a warfarin group (n = 191) and NOAC group (n = 141). The incidence of ICH-d in the warfarin group was 2.6% (5/191) and 2.1% (3/141) in the NOAC group (P = 0.77). There were no reversal agents administered, neurosurgical interventions, readmissions, or deaths in the NOAC group. CONCLUSIONS: Little is known about the impact of NOACs in the setting of trauma, especially regarding risks of ICH-d following traumatic injury. In the NOAC group, ICH-d occurred only 2.1% of the time. In addition, there were no reversal agents given, neurosurgical interventions, or deaths. These data, taken together, suggest the limited utility of repeat imaging in this patient population.

Sudden Loss of Vision: An Insight into Rivaroxaban.

A retrobulbar hemorrhage is a rapidly worsening emergent condition characteristically associated with significant orbital or facial trauma. Spontaneous hemorrhage into the retrobulbar compartment is rare. If not managed in a timely manner, it can lead to permanent vision loss. Rivaroxaban is a directly acting oral anticoagulant (DOAC) that inhibits factor Xa and is widely used for stroke prevention in patients with non-valvular atrial fibrillation (AFib).

Factor XI inhibition fulfilling the optimal expectations for ideal anticoagulation.

INTRODUCTION: Thromboembolic diseases are leading cause of mortality accounting for an estimated 1 in 4 deaths all over the world. Anticoagulation remains the mainstay of prevention and treatment of venous thromboembolic disorders. Conventional anticoagulants have been efficiently used over the last decades, but their clinical use encounters safety and convenience issues. To overcome these limitations, research have focused on development of new targets for anticoagulation leading to a relatively new class of drugs, non-vitamin K antagonist oral anticoagulants, specifically targeting activated factor X and thrombin. However, the search for more potent anticoagulant agents with reduced bleeding risk is still continuing. Areas covered: In this review, we provide an overview on emerging investigational anticoagulant drugs targeting factor XI in the coagulation cascade. We review data about the role of intrinsic pathway in thrombosis and haemostasis and the rationale of different pharmacodynamic approaches targeting factor XI. Expert opinion: Recent evidence suggests that the contact pathway plays a significant role in thrombosis by thrombus stabilization and growth without perturbing haemostasis. Factor XI might be a promising drug target to develop highly effective antithrombotic therapy with safety bleeding profile. Most of these investigational agents are in early development phases, only few have reached early phase clinical trials.

Perioperative Considerations in the Management of Anticoagulation Therapy for Patients Undergoing Surgery.

PURPOSE OF REVIEW: As ambulatory surgery has become increasingly more common, the appropriate management of anticoagulation therapy in patients undergoing invasive procedures has become progressively more relevant to healthcare professionals. The purpose of this literature review is to provide an overview of current common anaticoagulants and their pharmacological properties and to evaluate recent relevant literature and bridging therapy and provide recommendations on risk-guided therapy. RECENT FINDINGS: With the development of new drugs and the advancing study and practice of anticoagulation use, clinicians must keep up-to-date on the optimal management of patients requiring anticoagulation. NOACs and warfarin continue to be the mainstays of treatment, with varying timelines regarding when to hold administration of the different agents within the perioperative period. There are numerous factors that are considered in patients with multiple comorbidities including the risk for stroke on long-term anticoagulation and risk for thromboembolism, particularly in the perioperative setting when certain medication regimens may be altered and/or briefly held. There is ongoing investigation whether certain NOACs have more efficacy or greater safety profiles, depending on the degree of surgical intervention.

Epistaxis in the setting of antithrombotic therapy: A comparison between factor Xa inhibitors, warfarin, and antiplatelet agents.

OBJECTIVES/HYPOTHESIS: To describe the characteristics and severity of epistaxis in patients taking factor Xa inhibitors novel anticoagulants. STUDY DESIGN: Retrospective cohort study. METHODS: A study of adult patients hospitalized due to spontaneous epistaxis under the treatment of warfarin, rivaroxaban, or apixaban between the years 2011 and 2017 was performed. A control group of patients under antiplatelet therapy (acetylsalicylic acid, clopidogrel) was included. The mean follow-up periods in the warfarin, rivaroxaban, apixaban, and antiplatelet groups were 18, 14.5, 13.5, and 18.2 months, respectively. We compared demographics, location and severity of bleeding, treatment methods, and outcome between the groups. RESULTS: The study included 109 patients (35 under factor Xa inhibitors), the majority of whom presented with anterior epistaxis (68%). The antiplatelet group had more episodes of epistaxis prior to admission, and required endoscopic surgical control of bleeding more often, in comparison with anticoagulants (2.23 vs. 1.44, P < .05 and 23% vs. 6%, respectively, P < .05). Among anticoagulants, combined therapy (cauterization and packing) was required more frequently in the apixaban group compared to the rivaroxaban and warfarin groups (64% vs. 25% and 33%, respectively, P < .05). The rate of readmissions due to epistaxis, within 1 year of follow-up was lower in the factor Xa inhibitor groups compared with the warfarin and antiplatelet groups (16% vs. 9% and 4%, respectively, P < .05). Cessation of factor Xa inhibitor therapy was effective and uneventful with no further epistaxis events. CONCLUSIONS: Epistaxis under factor Xa inhibitors was effectively treated with no worse and perhaps even a better outcome when compared to other anticlotting medications. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:119-123, 2019.

Reversal of Novel Anticoagulants in Emergent Surgery and Trauma: A Comprehensive Review and Proposed Management Algorithm.

Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC's anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

Antithrombotic management after transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is now the accepted standard of care for patients with symptomatic severe aortic stenosis at elevated risk for conventional surgical valve replacement. Currently, societal guidelines propose the use of dual antiplatelet therapy for the prevention of thromboembolic events after TAVI in patients without an indication for oral anticoagulation. This strategy is empiric and largely based on expert consensus extrapolated from the arena of percutaneous coronary intervention. In this review, we explore the rational for using antiplatelet and/or anticoagulant strategies after TAVI, review current guidelines and the evidence underpinning them, and detail the on-going randomized trials that will shape future recommendations on this important issue.

The Efficacy and Safety of Rivaroxaban and Dalteparin in the Treatment of Cancer Associated Venous Thrombosis.

Venous thromboembolism (VTE) is a complication of malignancy that is associated with significant mortality. The CLOT trial showed superiority of dalteparin in comparison to warfarin in preventing VTE recurrence. Rivaroxaban has been approved for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). In the absence of large randomized trials in the oncology population, the efficacy and safety of rivaroxaban for the treatment of VTE in cancer patients needs to be assessed. A single-center retrospective chart review was conducted to assess the efficacy and safety of rivaroxaban compared with dalteparin in cancer-associated thrombosis. Out of 671 patients identified, 286 patients (107 in the rivaroxaban group and 179 in the dalteparin group) were eligible for analysis. The rivaroxaban group had a rate of VTE recurrence at 6 months of 4.9 versus 11.1% with dalteparin (p = 0.252). The incidence of recurrent DVT at 6 months was lower in patients treated with rivaroxaban (0%) compared with dalteparin (8.2%) at 6 months (p = 0.025). Incidence of recurrent PE in the rivaroxaban group (5%) versus dalteparin group (3.1%) at 6 months was not statistically significant (p = 0.675). No significant difference was identified between the rivaroxaban group and dalteparin group in the rate of major bleeding (2.8 vs. 1.1%, respectively). Rivaroxaban was comparable to dalteparin in prevention of VTE recurrence while having no significant differences with major or minor bleeding.

Enzymatic and chemical synthesis of new anticoagulant peptides.

In this study we report the enzymatic synthesis of N-α-[Carbobenzyloxy]-Tyr-Gln-Gln (Z-YQQ), a new anticoagulant tripeptide. It was obtained using phytoproteases from the stems and petioles of Asclepias curassavica L. as catalyst in an aqueous-organic biphasic system formed by 50% (v/v) ethyl acetate and 0.1 M Tris-HCl buffer pH 8. The resulting peptide was compared with the analogous peptide Tyr-Gln-Gln (YQQ) produced by solid-phase chemical synthesis. The in vitro anticoagulant activity of the aforementioned peptides was determined using Wiener Lab Test (Wiener, Argentina). The toxicological activity of the peptides was also determined. The enzymatically synthesized Z-YQQ peptide acted on the extrinsic pathway of the coagulation cascade, delaying the conversion time of prothrombin to thrombin and fibrinogen to fibrin by 136 and 50%, respectively, with respect to the controls. The chemically synthesized YQQ peptide acted specifically on the intrinsic pathway of the coagulation cascade, affecting factors VIII, IX, XI, and XII from such cascade, and increasing the coagulation time by 105% with respect to the control. The results suggest that two new anticoagulant peptides (Z-YQQ and YQQ) can be useful for safe pharmaceutical applications. Nevertheless, some aspects related to peptide production should be optimized. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1093-1101, 2018.

Morbidity and mortality after fragility hip fracture surgery in patients receiving vitamin K antagonists and direct oral anticoagulants.

INTRODUCTION: Early surgical treatment is recommended to reduce morbidity and mortality in patients with fragility hip fractures. Anticoagulation treatment poses a surgical challenge. While the action of vitamin K antagonists (VKAs) can be reversed, for direct oral anticoagulants (DOACs) antidote is only available for dabigatran. We aimed to assess the outcomes of patients treated with VKAs or DOACs undergoing surgical treatment for fragility hip fractures. MATERIALS AND METHODS: A retrospective study of patients presenting with proximal femoral fractures between January 2012 and June 2016. Patients with VKAs received vitamin-K. Primary outcomes were 1-year and in-hospital mortality. Secondary outcomes were time to surgery, in-hospital complications, need for blood transfusions and 1-year readmissions. RESULTS: Seven-hundred seventy-nine patients (796 hips) were included; 103 received VKAs, 47 DOACs and 646 no-anticoagulation. No difference between the 3 groups was noted with respect to patients' demographics or surgery type. Charlson's comorbidity index was higher for the DOACs group. Patients under anticoagulation were delayed to theater (Surgery < 48 h in 51% DOACs and 59% VKAs patients vs. 92% of no-anticoagulation, p < 0.001). Neither in-hospital nor 1-year mortality differed between groups. No other outcome measures differed, except for more wound infections in VKAs patients. CONCLUSIONS: While preoperative anticoagulation delays surgery following fragility hip fractures, this delay was not found to be related to increased morbidity or mortality. DOACs-treated patients did not have adverse outcomes compared to VKAs-treated patients despite the irreversibility of their treatment.

An Update on Anticoagulation in Atrial Fibrillation.

Cerebrovascular accidents related to atrial fibrillation (AF) are potentially preventable with anticoagulation. Until recently, warfarin was the only proven anticoagulant to be effective in stroke prevention, however the novel, direct acting oral anticoagulants (DOACs) are now available, triggering a paradigm shift in treatment philosophy. Today, physicians need to consider in which patients anticoagulation should not be used rather than, as in the past, deciding in which patients it should be used. Although warfarin will continue to have a place in managing some patients with AF, in the future, the DOACs should be the predominant therapy for stroke prevention in patients with non-valvular AF.

Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management.

Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b.i.d), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.

Antiplatelets and anticoagulants in vitreoretinal surgery, with a special emphasis on novel anticoagulants: a national survey and review.

PURPOSE: To survey current practice and opinion regarding the cessation of antiplatelet and anticoagulant agents prior to vitreoretinal surgery, with special emphasis on novel anticoagulants, and to provide an overview of current literature. METHODS: An online survey was sent to 167 members of the British and Eire Association of Vitreoretinal Surgeons (BEAVRS). A literature search and analysis was conducted on studies that reviewed the bleeding risk of antiplatelet and anticoagulant agents. RESULTS: The majority (93% for aspirin, 82% for clopidogrel) of respondents would not suspend antiplatelet administration, and 79% would not stop warfarin before vitreoretinal surgery. Regarding the novel anticoagulants (factor Xa inhibitors), 58% would not stop them, and 24% were unsure. Eighty-three percent of the surgeons were not confident regarding the management of factor Xa inhibitors preoperatively. Thirty-one percent of the respondents felt that anticoagulation cessation was independent of the type of vitreoretinal surgery, whereas 9% each felt that they would stop anticoagulation if possible for diabetic vitrectomy and retinectomy. Published evidence suggests that antiplatelet agents and warfarin do not confer a significantly greater risk of intra- or perioperative bleeding. Evidence regarding the novel anticoagulants is sparse. CONCLUSIONS: Further evaluation of novel anticoagulants in vitreoretinal surgery is required in order to provide evidence-based recommendations and address variations in practice.