Updated Assessment of Practice Patterns of Perioperative Management of Antiplatelet and Anticoagulant Therapy in Interventional Pain Management.

BACKGROUND: The role of antiplatelet/anticoagulant therapy is well known for its primary and secondary prevention of sequela from cardiovascular disease by decreasing the incidence of acute cerebral, cardiovascular, peripheral vascular, and other thrombo-embolicevents. The overwhelming data show that the risk of thrombotic events is significantly higher than that of bleeding during surgery after antiplatelet drug discontinuation. It has been assumed that discontinuing antiplatelet therapy prior to performing interventional pain management techniques is a common practice, even though doing so may potentially increase the risk of acute cerebral and cardiovascular events. A survey of practice patterns was conducted in 2012, since then the risks associated with thromboembolic events and bleeding, has not been systematically evaluated. OBJECTIVE: To conduct an updated assessment of the perioperative antiplatelet and anticoagulant practice patterns of U.S. interventional pain management physicians and compare this with data collected in 2012 with 2021 data regarding practice patterns of continuing or discontinuing anticoagulant therapy. STUDY DESIGNn: Postal survey of interventional pain management physicians. STUDY SETTING: Interventional pain management practices in the United States. METHODS: The survey was conducted based on online responses of the members of the American Society of Interventional Pain Physicians (ASIPP) in 2021. The survey was designed similar to the 2012 survey to assess updated practice patterns. RESULTS: The questionnaire was sent out to 1,700 members in October 2021. Out of these, 185 members completed the survey, while 105 were returned due to invalid addresses. The results showed that 23% changed their practice patterns during the previous year. The results also showed that all physicians discontinued warfarin therapy with the majority of physicians accepting an INR of 1.5 as a safe level. Low dose aspirin (81 mg) was discontinued for 3 to 7 days for low-risk procedures by 8% of the physicians, 34% of the physicians for moderate or intermediate risk procedures, whereas they were discontinued by 76% of the physicians for high-risk procedures. High dose aspirin (325 mg) was discontinued at a higher rate. Antiplatelet agents, including dipyridamole, cilostazol, and Aggrenox (aspirin, extended-release dipyridamole) were discontinued from 3 to 5 days by 18%-23% of the physicians for low-risk procedures, approximately 60% of the physicians for moderate or intermediate-risk procedures, and over 90% of the physicians for high-risk procedures. Platelet aggregation inhibitors clopidogrel, prasugrel, ticlopidine, and ticagrelor were discontinued for 3 to 5 days by approximately 26% to 41% for low-risk procedures, almost 90% for moderate or intermediate-risk procedures, and over 97% for high-risk procedures. Thrombin inhibitor dabigatran was discontinued by 33% of the physicians for low-risk procedures, 92% for moderate or intermediate-risk procedures, and 99% for high-risk procedures. Anti-Xa agents, apixaban, rivaroxaban, and Edoxaban were discontinued in over 25% of the physicians for low-risk procedures, approximately 90% for moderate or intermediate-risk procedures, and 99% for high-risk procedures. LIMITATIONS: This study was limited by its being an online survey of the membership of one organization in one country, that there was only a 11.6% response rate, and the sample size is relatively small. Underreporting in surveys is common. Further, the incidence of thromboembolic events or epidural hematomas was not assessed. CONCLUSION: The results in the 2021 survey illustrate a continued pattern of discontinuing antiplatelet and anticoagulant therapy in the perioperative period. The majority of discontinuation patterns appear to fall within guidelines.

Warfarin analogs target disulfide bond-forming enzymes and suggest a residue important for quinone and coumarin binding.

Disulfide bond formation has a central role in protein folding of both eukaryotes and prokaryotes. In bacteria, disulfide bonds are catalyzed by DsbA and DsbB/VKOR enzymes. First, DsbA, a periplasmic disulfide oxidoreductase, introduces disulfide bonds into substrate proteins. Then, the membrane enzyme, either DsbB or VKOR, regenerate DsbA's activity by the formation of de novo disulfide bonds which reduce quinone. We have previously performed a high-throughput chemical screen and identified a family of warfarin analogs that target either bacterial DsbB or VKOR. In this work, we expressed functional human VKORc1 in Escherichia coli and performed a structure-activity-relationship analysis to study drug selectivity between bacterial and mammalian enzymes. We found that human VKORc1 can function in E. coli by removing two positive residues, allowing the search for novel anticoagulants using bacteria. We also found one warfarin analog capable of inhibiting both bacterial DsbB and VKOR and a second one antagonized only the mammalian enzymes when expressed in E. coli. The difference in the warfarin structure suggests that substituents at positions three and six in the coumarin ring can provide selectivity between the bacterial and mammalian enzymes. Finally, we identified the two amino acid residues responsible for drug binding. One of these is also essential for de novo disulfide bond formation in both DsbB and VKOR enzymes. Our studies highlight a conserved role of this residue in de novo disulfide-generating enzymes and enable the design of novel anticoagulants or antibacterials using coumarin as a scaffold.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation in End-Stage Renal Disease on Hemodialysis: A Meta-Analysis of Randomized Control Trials.

End-stage renal disease (ESRD) and atrial fibrillation (AF) are commonly encountered, with ESRD itself serving as a well-established risk factor for AF.1 The 2018 AF guidelines have recommended apixaban across all the spectrums of renal impairment, including patients on hemodialysis (HD), and the 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society updated guidelines have suggested careful consideration of reduced dose of direct oral anticoagulants (DOACs) in patients with ESRD.2,3 The current data on the safety and efficacy of warfarin versus DOACs in patients with AF with ESRD and HD is variable. This study aimed to perform a study-level meta-analysis to evaluate the effectiveness and safety of warfarin and DOACs in patients with AF who require dialysis.

Multichannel Resonant Acoustic Rheometry System for Rapid and Efficient Quantification of Human Plasma Coagulation.

Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative assessment of plasma coagulation by monitoring the entire dynamic process in real time. Here, we report the development of a multichannel RAR (mRAR) system for simultaneous monitoring of the coagulation of multiple small-volume plasma samples, a capability that is critical to efficiently provide improved assessment of coagulation. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and an electronic driving system that controlled the generation of synchronized ultrasound pulses for real time monitoring of multiple samples simultaneously. The mRAR system was tested using Coumadin-treated plasma samples with a range of International Normalized Ratio (INR) values, as well as normal pooled plasma samples. Tracking of dynamic changes in clotting of plasma samples triggered by either kaolin or tissue factor was performed for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including clotting time, clotting speed, and the mechanical properties of the clots that were consistent with Coumadin dose and INR levels Data from this study demonstrate the feasibility of the mRAR system for the rapid, efficient, and accurate characterization of plasma coagulation.

Anatomy of the left atrial appendage for the interventional cardiologist.

Exact knowledge of the anatomy of the left atrial appendage (LAA) is crucial for LAA isolation by catheter ablation and for interventional LAA occlusion in patients with atrial fibrillation. This review outlines the current anatomical understanding of LAA morphology from ostium to distal lobes, myocardial fiber orientation and wall structure, and adjacent structures such as the left upper pulmonary vein with the Coumadin ridge, the circumflex artery with its side branches, the aortic root, pulmonary artery, and the pericardial space. Insight into these details will facilitate these interventions and reduce the risk of complications.

High versus low fixed-dose four factor-prothrombin complex concentrate for warfarin reversal in patients with intracranial hemorrhage.

BACKGROUND: Four-factor prothrombin complex concentrate 4F-PCC is the standard of care for warfarin reversal in patients with major bleed or requiring urgent surgery. Although the 4F-PCC dose is weight and international normalized ratio (INR) based, for practical purposes, a fixed-dose approach has been explored, especially for rapid reversal. We report our experience using two different fixed-dose 4F-PCC for warfarin reversal in patients presenting with intracranial hemorrhage (ICH). STUDY DESIGN AND METHODS: We completed a retrospective chart review comparing high (4000 units) versus low (2000 units) dose 4F-PCC by evaluating patient characteristics, laboratory data, and pre-and post-4F-PCC brain imaging. RESULTS: There was no significant difference between patient characteristics or INR correction (≤1.5) between the two groups. Eighty percent (12/15) of patients who received the low dose 4F-PCC had either improved or stable brain imaging as compared to 88% (14/16) of patients who received the high dose PCC. When the eight patients (4 from each arm of the study) who required neurosurgery were excluded, only two patients in each arm had worse imaging after 4F-PCC. CONCLUSION: There was no significant difference between the INR correction and the brain imaging changes in patients with an ICH who received either the high or the low fixed-dose 4F-PCC for warfarin reversal.

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BACKGROUND: Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT). METHODS: The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months. RESULTS: In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection.

OBJECTIVES: Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD). METHODS: This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation. RESULTS: Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99). CONCLUSIONS: Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.

Risk factors associated with warfarin overdose and complications related to warfarin overdose in the emergency department.

The aim of this study was to investigate risk factors of bleeding and mortality in patients with warfarin overdose (WOD). Totally, 783 patients were included, of which, 272 patients (34.7%) with an INR below 5,364 patients (46.5%) with an INR between 5-10, and 147 patients (18.8%) with an INR of 10 or above. Demographic, clinical, and laboratory findings of the patients were obtained from the Real Life Data Provision Center and Hospital Information Management System. Admittance in autumn (OR = 1.75; p = 0.012), INR = 5-10 (OR = 2.65; p < 0.001), INR ≥ 10 (OR = 9.06; p < 0.001), and antiplatelet use alongside warfarin (OR = 1.93; p < 0.001) were found to be independent risk factors for bleeding in this study. The age (OR= 1.03; p = 0.005), bleeding (OR = 1.69; p = 0.020), primary hypertension (OR = 1.72; p = 0.031), and INR ≥ 10 (OR = 2.02; p = 0.025) were found to be independent risk factors for mortality. The cutoff value for INR in predicting bleeding was found to be >6.35 with 74.2% sensitivity and 72.7% specificity. The significant risk factors were determined in WOD development. INR level, autumn, and antiplatelet use were independently associated with bleeding due to WOD. In addition, bleeding, hypertension and INR levels were independently related to in-hospital-mortality due to WOD.

Direct-acting oral anticoagulants versus warfarin in relation to risk of gastrointestinal bleeding: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Direct-acting oral anticoagulants (DOACs) are increasingly used, with studies showing a lower risk of gastrointestinal bleeding (GIB), but overall data for GIB risk remains debatable. The objective was to assess non-fatal and fatal GIB risk in patients on DOACs compared with warfarin from randomized clinical trials (RCTs). METHODS: RCTs comparing warfarin and DOACs for various indications (atrial fibrillation, thromboembolism, insertion of mechanical heart valves) were included. The primary endpoint was any GIB event. Other clinical events, such as fatal GIB, and effects of age (≤60 years or older), time in therapeutic range for warfarin, and choice of individual DOACs on GIB risk, were also assessed. RESULTS: 14 RCTs were included, comprising 87,407 participants (DOACs n=46,223, warfarin control n=41,184). The risk of GIB with DOACs was similar to that of warfarin (relative risk [RR] 1.04, 95% confidence interval [CI] 0.85-1.27). Compared with warfarin, rivaroxaban (RR 1.23, 95%CI 1.03-1.48) and dabigatran (RR 1.38, 95%CI 1.12-1.71) had a higher risk of any GIB, whereas fatal GIB risk was lower in the DOACs group (RR 0.36, 95%CI 0.15-0.82). The risk of DOAC-related fatal GIB was lower in patients aged ≤60 years and in those with poor coagulation control (RR 0.39, 95%CI 0.15-0.98). CONCLUSIONS: DOACs compared with warfarin have a lower risk of fatal GIB, especially in those aged <60 years and those with poor coagulation control. However, the risk of GIB was comparable with warfarin and DOACs, except for rivaroxaban and dabigatran.

Narrow Therapeutic Index drugs: clinical pharmacology perspective.

OBJECTIVES: Historically, the identification of drugs with the Narrow Therapeutic Index (NTI) has been empirically based on the clinical practice. In general terms, NTI drugs can be defined based on the steepness of the dose-response relationship and the degree of overlap between the effective and the toxic concentrations. KEY FINDINGS: The current definition in the Code of Federal Regulations is based on animal data and as such lacks direct clinical relevance. By basing these criteria on those factors that affect the degree of separation of the concentrations that elicit the therapeutic and the adverse effects, it was attempted to avoid the vagaries inherent in preparing a list of individual drugs themselves. SUMMARY: The overall conclusions are: (1) The issue of NTI drugs is still highly controversial, (2) The lists of NTI drugs are arbitrary and (3) Variability may contribute to the safety and efficacy. The objectives are to (1) To facilitate consensus on the definition of a NTI, (2) To identify characteristics of NTI and (3) To develop criteria for identifying NTI. The FDA should consider not only the pharmacokinetics (PK) studies, but also comparative efficacy and safety studies, for the NTI drugs to further to try 'convince or educate' the prescribers.

Impact of body mass index on 90-day warfarin requirements: a retrospective chart review.

BACKGROUND: Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin. METHODS: This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18-24.9 kg/m2), Overweight (25-29.9 kg/m2), Obesity Class I (30-34.9 kg/m2), Obesity Class II (35-39.9 kg/m2), Obesity Class III (⩾40 kg/m2). The primary outcome was the mean 90-day warfarin dose required to maintain "intermediate control" or "good control" of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications. RESULTS: A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg (p = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR. CONCLUSION: As BMI increases, there is an increased chronic warfarin requirement to maintain "intermediate control" or "good control" of INR between 2 and 3 in an ambulatory care setting.

Calciphylaxis of the breast, mimicking advanced breast cancer with skin involvement.

Calciphylaxis, also known as calcific uremic arteriolopathy, is a condition most commonly seen in patients with End-stage Renal Disease. The pathophysiology of the condition is related to an elevated calcium-phosphate product. It associated with extensive calcification, especially of the media of arterioles. It most commonly presents with skin manifestations, especially in the abdomen. However, when it occurs in the breast, it can mimic an advanced breast malignancy. We report a case of a 34-year-old female who presented with an extensive lesion to the breast, initially thought to be a long-neglected breast carcinoma. However, it was ultimately diagnosed as calciphylaxis of the breast, and radiologic imaging (particularly ultrasound and mammography) were crucial in making the diagnosis. We make the case of the importance of radiologic imaging in diagnosing this condition.

Warfarin and food, herbal or dietary supplement interactions: A systematic review.

AIMS: To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. METHODS: A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences. RESULTS: A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death. CONCLUSION: While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.

Persistent Wound Drainage among Total Joint Arthroplasty Patients Receiving Aspirin vs Coumadin.

BACKGROUND: Persistent wound drainage (PWD) is one of the major risk factors for periprosthetic joint infections (PJI), arguably the most dreaded complications after a total hip and knee arthroplasty (THA and TKA). The aim of this study is to identify the rates of PWD among THA and TKA patients who received aspirin (ASA) or Coumadin for postoperative venous thromboembolism (VTE) prophylaxis. METHODS: Retrospective review of 5516 primary THA and TKA was performed. Patients with PWD were identified. Chi-square test was used to compare the incidences of PWD, 30-day VTE, and PJI at 6 months between the ASA and Coumadin groups. Multivariate regression model was used to identify independent risk factors for PWD using Charlson and Elixhauser comorbidity indexes. RESULTS: The prevalence of PWD was 6.4% (353/5516). Patients receiving ASA had lower incidence of PWD (3.2% vs 8.5%, P < .0001) while having comparable rates of 30-day VTE (1.3% vs 1.4%, P = .722) and PJI at 6 months (1.8% vs 1.4%, P = .233) compared to those receiving Coumadin. Risk factors for PWD were diabetes (odds ratio [OR], 19.3; 95% confidence interval [CI], 11.8-23.2), rheumatoid arthritis (OR, 15.3; 95% CI, 10.8-17.2), morbid obesity (OR, 13.2; 95% CI, 9.7-17.5), chronic alcohol use (OR, 3.5; 95% CI, 1.8-5.5), hypothyroidism (OR, 1.9; 95% CI, 1.1-3.2), and Coumadin (OR, 1.7; 95% CI, 1.2-2.2). CONCLUSION: Use of ASA is associated with significantly lower rates of PWD after THA and TKA when compared to Coumadin while being equally efficacious at preventing VTE. Coumadin was found to be an independent risk factor for PWD.

The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial.

PURPOSE: Without supporting evidence, clinicians commonly recommend that warfarin be taken in the evening. We conducted a randomized controlled trial to evaluate the effect of administration time (morning vs evening) on the stability of warfarin's anticoagulant effect. METHODS: A total of 236 primary care physicians serving 54 western Canadian communities mailed letters of invitation to all their warfarin-using patients. Eligible patients were community-dwelling warfarin users (any indication) with at least 3 months of evening warfarin use and no plans for discontinuation. Participants were randomized (by web-based allocation) to morning vs continued evening warfarin ingestion. We used the Rosendaal method to determine the proportion of time within therapeutic range (TTR) of the international normalized ratio (INR) blood test month 2 to 7 postrandomization vs the 6 months prerandomization. The primary outcome was the percent change in proportion of time outside target INR range (with an a priori minimum clinically important difference of ±20%). All analyses were intention to treat. RESULTS: Between March 8, 2015 and September 30, 2016, we randomized 109 participants to morning and 108 to evening warfarin use. TTR rose from 71.8% to 74.7% in the morning group, and from 72.6% to 75.6% in the evening group, for a change in TTR of 2.9% in the former vs 3.0% in the latter (difference, -0.1%; P = .97; 95% CI for the difference, -6.1% to 5.9%). The difference in percent change in proportion of time outside the therapeutic INR range (obtained via Hodges-Lehmann estimation of the difference in medians) was 4.4% (P = .62; 95% CI for the difference, -17.6% to 27.3%). CONCLUSIONS: Administration time has no statistically significant nor clinically important impact on the stability of warfarin's anticoagulant effect. Patients should take warfarin whenever regular compliance would be easiest.

A review of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery.

Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.

Anatomy of the left atrial ridge (coumadin ridge) and possible clinical implications for cardiovascular imaging and invasive procedures.

BACKGROUND: The left atrial ridge is a structure located in the left atrium between the left-sided pulmonary veins ostia and the orifice of the left atrial appendage. Since it was commonly misdiagnosed as a thrombus, the ridge is also known as the "coumadin" or "warfarin" ridge. The left atrial ridge is a potential source of arrhythmias and can be an obstacle in ablation procedures. This study aimed to provide information about the occurrence and spatial morphometric characteristics of the left atrial ridge. METHODS AND RESULTS: The macroscopic morphology of the left atrial ridge was assessed in 200 autopsied human hearts. The ridge was observed in 59.5% of specimens and was absent in the remaining 40.5% of cases. The mean length of the ridge was 22.4 ± 5.1 mm. It was wider at its inferior sector when compared to its superior sector (9.1 ± 5.0 vs 7.9 ± 3.2 mm; P = .028). The total wall thickness measured at the cross section of the ridge was significantly larger in the inferior than in superior sector (6.2 ± 3.5 vs 4.3 ± 1.8 mm; P < .001), although the myocardial thickness was significantly larger at the superior sector (3.1 ± 1.4 vs 1.9 ± 0.9 mm in inferior sector, P < .001). CONCLUSION: The left atrial ridge is a variable structure, present in 59.5% of humans. The ridge is significantly wider and thicker at its inferior sector, although the actual myocardial layer present within the ridge is thinner at this location. Knowledge about the left atrial ridge morphology is key in avoiding unnecessary interventions or complications during invasive procedures.