Search

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement. [ABSTRACT FROM AUTHOR]

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period. Clinical registration number: ClinicalTrials.gov identifier: NCT05077124. [ABSTRACT FROM AUTHOR]

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08–1.52) and absence of headache (aOR 0.47; 95% CI 0.27–0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09–7.16), all-cause-death (aOR 7.56 95% CI 3.24–17.64), and major hemorrhage (aOR 3.70 95% CI 1.76–7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer. Highlights: Among 1,023 patients with cerebral vein thrombosis from the ACTION-CVT study, 6.5% had cancer. Older age and absence of headache were independently associated with cancer. Cancer patients had worse outcomes. [ABSTRACT FROM AUTHOR]

Moderate-strong CYP3A4 or Pgp inhibitors and inducers alter direct oral anticoagulant (DOAC) pharmacokinetics. Whether the presence of a DOAC drug-drug interaction (DDI) prompts in- hospital changes in management remains unknown. We identified all hospitalized patients at our institution who were admitted with a clinically relevant DOAC DDI from 01/2021 to 06/2021. Clinically relevant DOAC DDIs were defined as those listed in the prescribing information or FDA CYP3A4/Pgp inhibitors clinical indexes. We assessed the prevalence of DOAC DDIs and categorized their management as: drug stopped, drug held, or drug continued. For drugs that were continued we assessed whether the dose of the DOAC or interacting drug was increased, decreased or unchanged during the admission. We ascertained the number of DOAC DDIs that prompted an automated prescribing alert in our electronic health record (EHR). Finally, we conducted a logistic regression model to compare users of DOACs with DDI who had their regimen adjusted versus those without adjustments, focusing on outcomes of rehospitalization and death, adjusting for age and gender. Among 3,725 hospitalizations with a DOAC admission order, 197 (5%) had a clinically relevant DOAC DDI. The DOAC and the interacting drug were continued at discharge for 124 (63%) hospitalizations. The most frequent adjustments were stopping the interacting drug (73%) and stopping the DOAC (15%). Only 7 (4%) of DOAC DDIs prompted an EHR alert. The adjusted odds ratios for rehospitalizations and death, respectively, among patients whose regimens were adjusted compared to those whose were not, were 1.29 (95% CI, 0.67 to 2.48; P = 0.44) and 1.88 (95% CI, 0.91 to 3.89; P = 0.09). Clinically relevant DDIs with DOACs occur infrequently among hospitalized patients and usually are managed without stopping the DOAC. The clinical impact of such DDIs and subsequent adjustments on thrombotic and hemorrhagic outcomes requires further investigation. [ABSTRACT FROM AUTHOR]

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases. [ABSTRACT FROM AUTHOR]

Background: All available recommendations about the management of antithrombotic therapies (ATs) in patients who experienced traumatic brain injury (TBI) are mainly based on expert opinion because of the lack of strength in the available evidence-based medicine. Currently, the withdrawal and the resumption of AT in these patients is empirical, widely variable, and based on the individual assessment of the attending physician. The main difficulty is to balance the thrombotic and hemorrhagic risks to improve patient outcome. Methods: Under the endorsement of the Neurotraumatology Section of Italian Society of Neurosurgery, the Italian Society for the Study about Haemostasis and Thrombosis, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care, and the European Association of Neurosurgical Societies, a working group (WG) of clinicians completed two rounds of questionnaires, using the Delphi method, in a multidisciplinary setting. A table for thrombotic and bleeding risk, with a dichotomization in high risk and low risk, was established before questionnaire administration. In this table, the risk is calculated by matching different isolated TBI (iTBI) scenarios such as acute and chronic subdural hematomas, extradural hematoma, brain contusion (intracerebral hemorrhage), and traumatic subarachnoid hemorrhage with patients under active AT treatment. The registered indication could include AT primary prevention, cardiac valve prosthesis, vascular stents, venous thromboembolism, and atrial fibrillation. Results: The WG proposed a total of 28 statements encompassing the most common clinical scenarios about the withdrawal of antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients who experienced blunt iTBI. The WG voted on the grade of appropriateness of seven recommended interventions. Overall, the panel reached an agreement for 20 of 28 (71%) questions, deeming 11 of 28 (39%) as appropriate and 9 of 28 (32%) as inappropriate interventions. The appropriateness of intervention was rated as uncertain for 8 of 28 (28%) questions. Conclusions: The initial establishment of a thrombotic and/or bleeding risk scoring system can provide a vital theoretical basis for the evaluation of effective management in individuals under AT who sustained an iTBI. The listed recommendations can be implemented into local protocols for a more homogeneous strategy. Validation using large cohorts of patients needs to be developed. This is the first part of a project to update the management of AT in patients with iTBI. [ABSTRACT FROM AUTHOR]

Background: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. Research question: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. Study design and methods: Patients with acute PE included in COPE—prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE—were classified as having active cancer, previous cancer, or no cancer. Results: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. Interpretation: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. Clinical trial registration: clinicaltrial.gov identifier: NCT03631810. [ABSTRACT FROM AUTHOR]

Purpose: Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission. Methods: In this single-center retrospective study, DOAC plasma concentrations of adult trauma patients were analyzed with specific calibrated anti-IIa (dabigatran) and anti-Xa (apixaban, edoxaban and rivaroxaban) tests within 4 h after hospital admission. Results: A total of 210 trauma patients, admitted between 2019 and 2022, were included in the analyses. Low DOAC levels < 30 ng/mL were detected in 13.3% of the patients. In 7.1% of the patients, DOAC plasma levels ranged between 300–399 ng/mL and further 7.1% exhibited plasma concentrations > 400 ng/mL. The highest incidence of high to very high DOAC plasma concentration was observed for patients on rivaroxaban and dabigatran. A moderate correlation was observed between dabigatran plasma concentration and estimated glomerular filtration rate (rho = − 0.5338, p = 0.0003). For rivaroxaban no clear association between plasma concentration and liver or renal function could be detected. Patients on statins had significantly higher DOAC concentration in comparison with those not taking statins (153 (76–274) vs 108 (51–217) ng/mL, p = 0.046). Conclusion: The current study revealed that patients on dabigatran and rivaroxaban were prone to higher DOAC plasma levels upon hospital admission in comparison with apixaban and edoxaban. DOAC plasma level measurement in trauma patients might be warranted due to unpredictively low or high plasma concentrations. However, the clinical impact of altered plasma levels on both, bleeding and thromboembolic events, remains to be determined by future studies. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. Patients and methods: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. Results: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). Conclusion: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted. [ABSTRACT FROM AUTHOR]

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80–0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives. [ABSTRACT FROM AUTHOR]

Background: The emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings. Objectives: We evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes. Methods: We performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled. Results: A primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42–2.01, p = 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51–3.64, p = 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08–1.93, p = 0.25). Conclusions: DOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation is a cornerstone in atrial fibrillation (AF) management for stroke prevention. Studies showed that oral anticoagulants (OAC), previously limited to warfarin, were underused. Recently, non-vitamin K oral anticoagulants (NOACs) have seen widespread adoption, but it has not been well studied whether there has been a subsequent increase in OAC usage in AF patients. Methods: We quantified OAC rates in AF patients in a large multispecialty health system in the Northeast United States. A total of 351,795 patients seen in the network over the preceding 18 months were reviewed. Results: Of these patients, 8727 (2.5%) carried a diagnosis of AF, and, of the 6933 patients with a CHA2DS2-VASc score of 2 or higher, 5576 (80.4%) had an OAC listed as an active medication or had received a left atrial appendage occlusion device. Of the 6605 patients treated with an OAC, 5308 (80.4%) were treated with a NOAC and 1295 (19.6%) were prescribed warfarin. A higher percentage of patients with CHA2DS2-VASc ≥ 2 who had seen a cardiologist were treated with an OAC vs. those who had not seen a cardiologist in the prior 18 months (83.95% vs. 67.43%, p < 0.01). Conclusions: We show dramatically increased OAC usage among patients with AF and that NOACs comprise the large majority of OACs compared with previous studies. This suggests an association between widespread adoption of NOACs and increased oral anticoagulation rates. Future directions include assessing barriers to oral anticoagulation and developing interventions to reduce disparity in OAC use between clinics. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The aim of this clinical observational study was to assess the efficacy of L-PRF as a hemostatic agent in patients under treatment with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Materials and methods: Patients under oral anticoagulant therapy (VKA or DOACs) who needed a single simple tooth extraction were enrolled. L-PRF plug was positioned inside the alveolus and secured with non-absorbable sutures. Surgical time, pain-VAS, paracetamol intake, intra-operative, post-operative biological complications, and bleeding events have been registered. Results: A total of 112 patients (59 patients for DOAC and 53 for VKA group) were enrolled. Post-operative bleeding was recorded in nine patients (17%) for VKA group and nine patients (15.3%) for DOACs group. None of the patients needed a medical support for managing of bleeding. Seven days after surgery, no cases of post-extractive complications occurred. Conclusions: The use of L-PRF resulted in limited mild late post-operative bleedings without the need of medical intervention. Clinical relevance: The use of L-PRF can be adopted for an uneventful post-operative curse in anticoagulated patients without chasing their therapy for single tooth extraction. [ABSTRACT FROM AUTHOR]

Background: Despite their effectiveness and ease of use, medication errors have been reported to be highly prevalent with direct-acting oral anticoagulants (DOAC). Aim: The aim of this study was to explore views and experiences of pharmacists on contributory factors and mitigation strategies around medication errors in relation to DOAC. Method: This study used a qualitative design. Semi-structured interviews were conducted with hospital pharmacists in Saudi Arabia. The interview topic guide was developed based on previous literature and Reason's Accident Causation Model. All interviews were transcribed verbatim and MAXQDA Analytics Pro 2020 was used to thematically analyse the data (VERBI Software). Results: Twenty-three participants representing a range of experiences participated. The analysis recognised three major themes: (a) enablers and barriers faced by pharmacists in promoting safe utilisation of DOAC, such as opportunities to conduct risk assessments and offer patient counselling (b) factors related to other healthcare professionals and patients, such as opportunities for effective collaborations and patient health literacy; and (c) effective strategies to promote DOAC safety such as empowering the role of pharmacists, patient education, opportunities for risk assessments, multidisciplinary working and enforcement of clinical guidelines and enhanced roles of pharmacists. Conclusion: Pharmacists believed that enhanced education of healthcare professionals and patients, development and implementation of clinical guidelines, improvement of incident reporting systems, and multidisciplinary team working could be effective strategies to reduce DOAC-related errors. In addition, future research should utilise multifaceted interventions to reduce error prevalence. [ABSTRACT FROM AUTHOR]

Purpose: Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds. Methods: We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin. Results: The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in a statistically significant way (hazard ratio [HR] 1.7 and p value 0.431). Similarly, the incidence of nonmajor and major bleeds in patients on DOACs compared to those on warfarin was also not increased in a statistically significant way (HR for nonmajor bleeds in DOAC patients was 2.8 with a p value of 0.167 and the HR for major bleeds was 2.0 with a p value 0.267). In multivariate analysis, congestive heart failure (CHF) was a risk factor for TEs across both groups (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3–17.6) and bleed history was a risk factor for clinically significant bleeds (OR = 6.8, 95% CI = 2.7–17.2). Conclusion: In this small, retrospective multicenter study, the use of DOACs did not increase the risk of TEs or clinically significant bleeds compared to warfarin in a statistically significant way. [ABSTRACT FROM AUTHOR]

Background: There is an ever-increasing number of hip fracture (HF) patients on direct oral anticoagulants (DOAC). The impact of DOAC plasma level prior to HF surgery on perioperative blood loss and transfusion requirements has not been investigated so far. Materials and methods: In this retrospective study of HF patients on DOACs admitted to the AUVA Trauma Center Salzburg between February 2015 and December 2021. DOAC plasma levels were analysed prior to surgery. Patients were categorized into four DOAC groups: Group A < 30 ng/mL, Group B 30–49 ng/mL, Group C 50–79 ng/mL, and Group D ≥ 80 ng/mL. Haemoglobin concentration was measured upon admission, prior to surgery, after ICU/IMC admission, and on day 1 and 2 post-surgery. Difference in the blood loss via drains, transfusion requirements and time to surgery were compared. Results: A total of 155 subjects fulfilled the predefined inclusion criteria. The median age of the predominantly female patients was 86 (80–90) years. Haemoglobin concentration in Group D was lower upon admissions but did not reach statistical significance. The decrease in haemoglobin concentration over the entire observation time was comparable between groups. Blood transfusion requirements were significantly higher in Group D compared to Group A and B (p = 0.0043). Time to surgery, intra- and postoperative blood loss via drains were not different among groups. Conclusion: No strong association between the DOAC plasma levels and perioperative blood loss was detected. Higher transfusion rates in patients with DOAC levels ≥ 80 ng/mL were primarily related to lower admission haemoglobin levels. DOAC concentration measurement is feasible and expedites time to surgery. [ABSTRACT FROM AUTHOR]

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212–1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266–1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658–0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095–2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin. [ABSTRACT FROM AUTHOR]

Since direct oral anticoagulants (DOAC) are administered frequently to an elderly, co-morbid population, medical emergencies including trauma, acute bleeding or organ failure are not uncommon. In these situations, the type, dosage or the time of last intake of anticoagulants is often unknown and single substance analysis by functional tests is only possible if the substance contained in the sample is known. A reliable and validated toxicology screen of DOAC and argatroban would be helpful inform not only attending physicians in the emergency department but also law enforcement and courts of justice. After precipitation with acetone, HPLC separation was achieved on a Phenomenex Luna Pentafluorophenyl Colum using acetonitrile–water (90:10, v/v) as mobile phase system. Detection was performed using a 3200 Q Trap mass spectrometer (AB Sciex). For analysis MRM Scans (MS/MS) with positive ionization were chosen. The method was validated for blank serum as the matrix of choice. Limits of detection are between 0.5 and 1.0 ng/mL, limits of quantification are between 1.9 and 3.6 ng/mL and recoveries are above 60%. The applicability of the method was demonstrated by the determination of DOAC in body fluids from forensic cases and in therapeutic drug monitoring. The rapid simultaneous detection and quantification of apixaban, argatroban, dabigatran etexilate, dabigatran, edoxaban and rivaroxaban in body fluids by HPLC–MS/MS closes an important gap in emergency toxicology. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and efficacy are scarce and contradictory. We systematically searched MEDLINE and Google Scholar databases from January 2010 to January 2021 for studies of DOACs in CTEPH. Three observational studies, 2 abstracts and one case series met our inclusion criteria. While these studies reported similar or even less rates of major bleeding in patients receiving DOACs compared with vitamin K antagonists, there were concerns about the possibility of increased risk of venous thromboembolism recurrence with DOAC therapy. Further studies are warranted to better define the role of DOACs in CTEPH. [ABSTRACT FROM AUTHOR]

This study audited prescribing practices for patients with acute venous thromboembolism (VTE) prior to and after being seen in an outpatient VTE clinic. This retrospective chart review conducted between June 2018 through May 2019 included patients with confirmed acute VTE, seen for an initial appointment. Exclusion criteria were patients with additional indications for anticoagulation, lack of information to determine primary outcome and active cancer. To assess practices, the time taken to be seen in clinic, anticoagulant therapies (prior to/following clinic) used and concordance of anticoagulant use with product monographs were assessed. Of the 325 (40.6%) patients included, the median age was 57.7 years, most were referred with pulmonary embolism (PE) (54.5%) and the majority of referrals came through the emergency department (45.2%). The median time to be seen in clinic was 13 days, with no differences in time between type of VTE or proximity of clot. Prior to being seen in VTE clinic, most were prescribed direct oral anticoagulants (DOACs) (81.9%), with a small portion receiving low molecular weight heparin (LMWH) (12.9%) and warfarin (5.2%). Most received anticoagulants concordant with product monographs (87.7%), with more discordance with warfarin (52.9%) and LMWH (14.3%) compared to DOACs (9.4%) (P < 0.001). At the initial VTE clinic visit, 70 (21.5%) patients had therapy changes, with most being from LMWH/warfarin to a DOAC (47.1%). Our data reflects high uptake of DOACs for acute VTE treatment with most prescribed in accordance with product monographs. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cerebral venous thrombosis (CVT) is a rare cause of stroke that most commonly affects younger women. Here, we review new literature relevant to the management and prognosis of individuals with CVT and ongoing areas of uncertainty. Recent Findings: Direct-acting oral anticoagulants (DOACs) are being increasingly integrated into routine care but are not yet recommended by guidelines. Recent randomized clinical trials and available case series offer reassuring safety data. Routine use of endovascular therapy is not associated with improved outcomes. The relationship between recanalization and prognosis is uncertain. Summary: The evidence base for management of CVT continues to improve. Ongoing areas of uncertainty include duration of therapy and whether certain subgroups of patients may benefit from neurointervention or personalized approaches to antithrombotic strategy. The state of knowledge will continue to benefit from large collaborative international efforts, and integration of patient partnerships to identify research priorities. [ABSTRACT FROM AUTHOR]

Background Direct oral anticoagulants (DOACs) have revolutionised anticoagulant pharmacotherapy. However, DOAC-related medication incidents are known to be common. Objective To assess medication incidents associated with DOACs using an error theory and to analyse pharmacists' contributions in minimising medication incidents in hospital in-patients. Setting A large University academic hospital in the West Midlands of England. Methods Medication incident data from the incident reporting system (48-months period) and pharmacists' interventions data from the prescribing system (26-month period) relating to hospital in-patients were extracted. Reason's Accident Causation Model was used to identify potential causality of the incidents. Pharmacists' intervention data were thematically analysed. Main outcome measure (a) Frequency, type and potential causality of DOAC-related incidents; (b) nature of pharmacists' interventions. Results A total of 812 reports were included in the study (124 medication incidents and 688 intervention reports). Missing drug/omission was the most common incident type (26.6%, n = 33) followed by wrong drug (16.1%, n = 20) and wrong dose/strength (11.3%, n = 14). A high majority (89.5%, n = 111) of medication incidents were caused by active failures. Patient discharge without anticoagulation supply and failure to restart DOACs post procedure/scan were commonly recurring themes. Pharmacists' interventions most frequently related to changes in pharmacological strategy, including drug or dose changes (38.1%, n = 262). Impaired renal function was the most common reason for dose adjustments. Conclusion Prescribers' active failure rather than system errors (i.e. latent failures) contributed to the majority of DOAC-related incidents. Reinforcement of guideline adherence, prescriber education, harnessing pharmacists' roles and mandating renal function information in prescriptions are likely to improve patient safety. [ABSTRACT FROM AUTHOR]

Purpose: To date, the optimal treatment for portal vein thrombosis (PVT) in cirrhotic patients has not been established in guidelines or consensus. We conducted a systematic review and meta-analysis to evaluate the effect of anticoagulation therapy in patients with cirrhosis and PVT. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched (until 31st October 2020) for studies evaluating the effect of anticoagulation therapy on treating PVT in patients with cirrhosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using the Mantel–Haenszel method. Results: A total of 13 studies were included in the analysis, comprising 6005 patients. Of these, three were prospective cohort studies, nine were retrospective cohort studies and one was case–control study. Compared to no treatment, anticoagulation therapy was associated with higher rates of PVT recanalization (OR 4.29; 95% CI 3.01–6.13). Anticoagulation therapy demonstrated a significant 74% reduction in PVT extension compared to no treatment (OR 0.26; 95% CI 0.14–0.49). Anticoagulation therapy was associated with a nonsignificantly lower risk of death (OR 0.53; 95% CI 0.20–1.40). However, anticoagulation therapy was associated with slightly higher risk of bleeding compared to no treatment (OR 1.16; 95% CI 1.02–1.32). Conclusions: In cirrhotic patients with PVT, anticoagulation therapy helps increase rate of PVT recanalization and improve survival, but may also carry higher risks of bleeding compared to no treatment. Our findings support the use of anticoagulation in cirrhotic patients with PVT. [ABSTRACT FROM AUTHOR]

Hemoadsorption was used in a 59-year-old patient with an acute type A aortic dissection, who was on rivaroxaban and dual antiplatelet therapy with clopidogrel and acetylsalicylic acid. Our aim was to expeditiously remove rivaroxaban preoperatively. After 8 h of hemoadsorption, the rivaroxaban blood plasma concentration (RBPC) did not decrease below 42.1 μg/l. Intraoperatively, hemoadsorption was repeated during extracorporeal circulation. Sixteen hours after surgery and a total of 13 h of hemoadsorption, the RBPC was 40.1 μg/l. Thereafter, the RBPC spontaneously decreased to 24.7 μg/l within 14 h. In our patient, hemoadsorption may have enhanced rivaroxaban removal at higher RBPC (cutoff value 40–50 μg/l). At lower RBPC, the removal of rivaroxaban may depend solely on the natural drug elimination process. The evolution of the RBPC under hemoadsorption in vivo warrants a thorough investigation. Further clinical studies are required to assess the effectiveness and limitations of hemoadsorption to preclude a fatal bleeding event in patients with rivaroxaban in need of major emergency surgery. [ABSTRACT FROM AUTHOR]

Despite an increasing number of patients suffering from an acute coronary syndrome under novel oral anticoagulant therapy, specific treatment recommendations for anticoagulation are still lacking. For this reason, the German Society of Cardiology and the German Association of Interdisciplinary Intensive Care and Emergency Medicine developed a consensus statement for the treatment of these patients with the aim to summarize the current evidence and to increase the safety of this special patient group. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p < 0.001). DOACs may be an alternative to warfarin for the treatment of LV thrombus based on a retrospective assessment of thromboembolic events and GUSTO bleeding events within 90 days of diagnosis of LV thrombus. However, further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: As left atrial appendage occlusion devices (LAAO) implantation rates grow, continued evaluation on best patient practices is important. We report pooled Watchman outcomes at a multicenter Texas healthcare system with an emphasis on clinical outcomes and post-implantation anticoagulation with direct oral anticoagulants (DOACs) versus warfarin.Methods: Data for 163 patients with atrial fibrillation (AF) undergoing Watchman implantation was collected via retrospective chart review between June 2016 and June 2018. A Fisher's exact test was utilized to evaluate associations in bivariate comparisons of categorical data. Tests of non-inferiority, applied between DOACs and warfarin, utilized a ratio of 2.Results: Outcomes were significant for similar rates of stroke, disabling stroke, major bleeds, and all-cause mortality when compared to published clinical trials. Most patients with cerebrovascular events were found to have >5 mm peri-device leaks (PDLs), were on warfarin at the time of the event (75%), and all occurred within the first 6 months post implant. A significant number of patients were discharged on DOACs (42%). DOACs were shown to be non-inferior to warfarin with respect to stroke (p = 0.0048), disabling stroke (p = 0.0383), gastrointestinal bleeding (p = 0.0287), mortality (p = 0.0165), and combined adverse outcomes (p = 0.0040). DOACs were associated with less combined adverse outcomes (p = 0.021).Conclusion: Our findings suggest that additional imaging or aggressive management of PDLs in Watchman recipients within the initial 6-month follow-up may aid in reducing stroke rates. Additionally, anticoagulation with DOACs' post Watchman implantation was found non-inferior to warfarin, with some evidence of lower risk for adverse outcomes favoring DOACs. [ABSTRACT FROM AUTHOR]

The introduction of direct oral anticoagulants (DOACs) to the market has expanded anticoagulation options for outpatient use. Routine evaluation by health care professionals is recommended as it is with warfarin, therefore requiring adjustments in practices of anticoagulation management services (AMS). This study aims to describe trends that occurred following the incorporation of DOACs into AMS at a large academic medical center. A retrospective chart review of pharmacist-run AMS was used to compare patients on DOAC therapy versus other types of anticoagulation, including warfarin and parenteral agents. Primary outcomes included trends in the number of unique patients, management encounters, and telephone encounters throughout the study period. Secondary outcomes included trends in new encounters, and changes in patient characteristics, resources utilized, and patient satisfaction scores. A total of 2976 unique patients, 74,582 management encounters, and 13,282 telephone encounters were identified. From study beginning to end, results showed stable numbers of unique patients, an increase in management encounters for the DOAC group and decrease in the other anticoagulants group, and stable numbers of telephone encounters. Additionally, the number of new encounters for both groups increased. Throughout the study, pharmacy resources were reallocated within anticoagulation to adapt to the changing trends and patient satisfaction reached targets. Patients' characteristics remained stable, with the DOAC group having fewer comorbid conditions and concomitant medications that could increase bleed risk. This study showed that by reallocating resources within anticoagulation, AMS can maintain stable patient populations while continuing to expand access and satisfy patients following DOAC inclusion. [ABSTRACT FROM AUTHOR]

Introduction: Older hip fracture patients are still challenging in daily clinical practice. Due to the high prevalence of osteoporosis and atrial fibrillation in this age group, the number of fragility fracture patients under oral anticoagulation (OAC) increases. The outcome is still disappointing, short- and long-term mortality and morbidity is high. The impact of pre-existing OAC is not yet clear, especially regarding new OAC drugs like Factor Xa inhibitors (FXa). The purpose of our study was to compare the short-term outcome of older hip fracture patients, without OAC (controls), on Vitamin K antagonists (VKA) and on FXa. Materials and methods: The study is a retrospective case–control study including patients older than 70 years who sustained hip fractures caused by an inadequate trauma and treated at a level 1 trauma center from February 2017 to June 2018. Patient's information was taken from patient's charts. 102 cases were analysed, 61 controls, 41 on OAC (15 on VKA and 26 on FXa). As outcome parameter we defined mortality, perioperative complications, bleeding, need of blood supplements, delay of surgery, length of stay, and a combined outcome parameter (mortality, myocardial infarction, stroke, thromboembolic events, blood preservations, re-vision surgery, major bleeding and decline of hemoglobin). Results: Eight patients died during hospital stay, in-hospital mortality was 7.8%. The highest mortality rate was found in patients on VKA (20%), compared to patients on FXa (3.8%) and controls (6.6%). However, mortality rate did not differ significantly within the groups. The combined endpoint was significantly more frequently seen in patients on OAC compared to controls (p = 0.006). No difference was observed between patients on VKA or FXa. Mean time to surgery and LOS was significantly longer in patients on OAC compared to controls. No significant differences were seen between VKA and FXa. Conclusions: In our study OAC was significantly associated with worse outcome compared to controls. Marginal differences were observed between patients on FXa or VKA. Further studies involving a higher number of patients are necessary to confirm our results. At that time, some our results have to interpreted carefully and need confirmation. [ABSTRACT FROM AUTHOR]

Purpose of review: Patients undergoing colonoscopy frequently require antithrombotic therapy for underlying cardiovascular disease. Antithrombotic therapy increases the risk of bleeding during or after colonoscopy, particularly when more invasive procedures are required. However, the risk of thrombosis—with possibly devastating consequences—is increased if antithrombotic agents are held. This review will highlight existing data on the balance of procedural and patient risk factors to guide endoscopists on the management of periprocedural antithrombotic therapy. Recent findings: Diagnostic colonoscopy has long been established to be low risk for hemorrhage even in patients on antithrombotic therapy, while colonoscopy with interventions—including polypectomy—is viewed as high risk requiring interruption of antithrombotic therapy when possible. Recent data, however, has challenged these practices and suggests that a more nuanced perspective may be necessary. For example, a recent randomly controlled trial found no difference in immediate or delayed hemorrhage between patients on dual antiplatelet therapy versus aspirin and placebo after polypectomy. Further, increasing data are emerging to suggest that small polypectomy (< 1 cm) is safe without interruption of anticoagulation with the use of cold snare polypectomy. Summary: In patients undergoing colonoscopy, the risk of hemorrhage must be weighed against the risk of thrombosis in patients with cardiovascular disease on antithrombotic agents. In general, low-risk procedures do not require interruption of antithrombotic agents, while high-risk procedures in low-risk patients require holding antithrombotic therapy. High-risk procedures in high-risk patients require individualized decision-making with increasing data helping to support which procedures can safely be performed. [ABSTRACT FROM AUTHOR]

Dabigatran etexilate is an oral direct thrombin (Factor IIa) inhibitor approved for patients with atrial fibrillation and for management of risk of deep vein thrombosis and pulmonary embolism. Dabigatran offers advantages over treatment with warfarin, including limited laboratory monitoring. It is equivalent in prevention of stroke and deep vein thrombosis with essentially equivalent complication rates. In contrast to warfarin, reversal of the anticoagulation is less well established. Idarucizumab is available for reversal, however supporting research is mixed; the agent also happens to be quite expensive making availability difficult. Hemodialysis has been proposed as a method of reversal, but this is difficult in patients with life threatening hemorrhage, and is not available at many hospitals. Intravenous fat emulsion (IFE) has been used for treatment of overdose of lipophilic drugs. Most toxicologists only recommend IFE for patients in extremis after ingestion of a lipid soluble substance. Dabigatran is lipid soluble, although the pro-drug more so than the active metabolite. The authors sought to see if dabigatran-induced coagulopathy of human in vitro blood samples could be reversed with IFE. Blood samples were spiked with dabigatran or dabigatran plus IFE. Values for Ecarin clot time (ECT—primary outcome), PT/INR, and aPTT, were compared across both study arms. A total of 18 healthy volunteers were included in our study. There were no significant differences in the ECT, PT/INR, and aPTT between the dabigatran arm and the dabigatran plus IFE arm. Based on these methods, IFE does not reverse dabigatran-induced coagulopathy. [ABSTRACT FROM AUTHOR]

Edoxaban, alongside other direct oral anticoagulants (DOAC), is increasingly used for prevention of thromboembolism, including stroke. Despite DOAC therapy, however, annual stroke rate in patients with atrial fibrillation remains 1–2%. Rapid exclusion of relevant anticoagulation is necessary to guide thrombolysis or reversal therapy but, so far, no data exists on the effect of edoxaban on available point-of-care test systems (POCT). To complete our previous investigation on global coagulation-POCT for the detection of DOAC, we evaluated whether CoaguChek®-INR (CC-INR) is capable of safely ruling out edoxaban concentrations above the current treatment thresholds of 30/50 ng/mL in a blood sample. We studied patients receiving a first dose of edoxaban; excluding subjects receiving other anticoagulants. Six blood samples were collected from each patient: before drug intake, 0.5, 1, 2 and 8 h after intake, and at trough (24 h). CC-INR and mass spectrometry for edoxaban concentrations were performed for each time-point. One hundred and twenty blood samples from 20 patients contained 0–302 ng/mL of edoxaban. CC-INR ranged from 0.9 to 2.3. Pearson's correlation coefficient showed strong correlation between CC-INR and edoxaban concentrations (r = 0.73, p < 0.001). Edoxaban concentrations > 30 and > 50 ng/mL were ruled out by CC-INR ≤ 1.0 and ≤ 1.1, respectively, with high specificity (> 95%), and a sensitivity of 44% (95%-confidence interval: 30–59%) and 86% (74–93%), respectively. Our study represents the first evaluation of coagulation-POCT in edoxaban-treated patients. CC-POCT is suitable to safely exclude clinically relevant edoxaban concentrations prior to thrombolysis, or guide reversal therapy in stroke patients. [ABSTRACT FROM AUTHOR]

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16–83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3–11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89–1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93–1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12–1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC. [ABSTRACT FROM AUTHOR]

The role of dedicated anticoagulation management services (AMS) for patients receiving direct oral anticoagulant (DOAC) therapy is unclear. The objective of our study was to describe DOAC management in patients who were and were not managed by an AMS. We conducted a retrospective cohort study among patients with atrial fibrillation at the University of Utah Health (UUH) who received DOAC therapy between January 2013 and June 2016. Patients in the AMS group were managed by a pharmacist-led AMS whereas those in the non-AMS group were managed by other providers. The number and type of provider encounters and interventions related to DOAC therapy and a composite endpoint of thromboembolism, bleeding, and all-cause mortality were recorded. Overall, 90 and 370 patients were managed in the AMS and non-AMS groups, respectively. AMS group patients had greater chronic disease burden as measured by the Charlson comorbidity index. AMS group patients had more frequent DOAC-related encounters than non-AMS group patients but both groups had similar DOAC therapy intervention rates. Over half of patients in the AMS group received potentially duplicative interventions from their regular clinicians. The composite endpoint occurred in 18.9% and 13.5% of AMS and non-AMS group patients, respectively (p = 0.29). Patients managed by AMS providers were more complex and had more frequent encounters regarding their DOAC therapy than those managed by non-AMS providers. However, there was evidence of duplicative DOAC therapy management efforts. No difference between AMS and non-AMS groups in the composite clinical endpoint was detected. [ABSTRACT FROM AUTHOR]

For some years now, direct-acting oral anticoagulants (DOACs) have entered the clinical practice for stroke prevention in non-valvular atrial fibrillation (NVAF) or for prevention and treatment of venous thromboembolism (VTE). However, there is uncertainty on DOACs' use in some clinical scenarios that are not fully explored by clinical trials, but commonly encountered in the real world. We report a Delphi Consensus on DOAC use in VTE patients. The consensus dealt with seven main topics: (1) clinical superiority of DOACs compared to VKAs; (2) therapeutic options for patients with intermediate risk PE; (3) therapeutic management of patients with deep vein thrombosis (DVT); (4) DOACs' role in oncological patients with VTE; (5) role of the reversal agent; (6) safety of low doses of DOACs in VTE patients; (7) DOACs long-term therapy (more than 12 months) in VTE patients; Forty-six physicians (cardiologists, internists, angiologists, oncologists, hematologists, and geriatricians) from Italy expressed their level of agreement on each statement by using a five-point Likert scale (1: strongly disagree, 2: disagree, 3: somewhat agree, 4: agree, 5: strongly agree). Votes 1–2 were considered as disagreement, while votes 3–5 as agreement. For each statement an agreement of ≥ 66% among the respondents was considered consensus. A brief discussion about the results for each topic is also reported. [ABSTRACT FROM AUTHOR]

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. The recent spreadout of the COVID-19 pandemic requires a re-organization of Anticoagulation Clinics to prevent person-to-person viral diffusion and continue to offer the highest possible quality of assistance to patients. In this paper, based on the Italian Federation of Anticoagulation Clinics statements, we offer some advice aimed at improving patient care during COVID-19 pandemic, with particular regard to the lockdown and reopening periods. We give practical guidance regarding the following points: (1) re-thinking the AC organization, (2) managing patients on anticoagulants when they become infected by the virus, (3) managing anticoagulation surveillance in non-infected patients during the lockdown period, and (4) organizing the activities during the reopening phases. [ABSTRACT FROM AUTHOR]

Introduction: The management of patients with a hip fracture is affected by the use of oral anticoagulants. A cross-sectional analysis was undertaken to investigate health outcome differences in those anticoagulated compared to those not anticoagulated.Methods: Patients aged 50 years and over presenting to a large university hospital with hip fractures were identified from the service registry. Patient characteristics and health outcomes between those not anticoagulated were compared with those anticoagulated (warfarin and direct oral anticoagulants, DOAC).Results: 200/2307 (9%) patients were anticoagulated. 84% were on warfarin, and the rest a DOAC. Compared to those anticoagulated, there was a higher prevalence of dementia (25% vs. 18%, p = 0.02) and a lower prevalence of cardiovascular disease (54% vs. 78%, p < 0.01), atrial fibrillation (10% vs. 82%, p < 0.01), and polypharmacy (55% vs. 76%, p < 0.01). Renal function was lower in the anticoagulated group. Time to operation for those not anticoagulated and anticoagulated was a median (IQR) of 25 (15) and 27 (18) hours. There was no difference in blood transfusion and hospital mortality. Postoperative complications were similar except a higher rate of renal failure (14% vs. 19%, p = 0.04) and heart failure (1% vs. 5%, p < 0.01), and a longer length of stay [median (IQR): 14 (10) vs. 16 (12) days] in the anticoagulated group. This was no longer significant after adjustment of confounders.Conclusion: There was no statistically significant difference in health outcomes between those anticoagulated and those not after adjusting for patient characteristics. It was feasible to avoid significant delay in hip fracture surgery in those anticoagulated. [ABSTRACT FROM AUTHOR]

Recent guidelines recommend direct acting oral anticoagulants (DOAC) over vitamin-k antagonist (VKA) for acute venous thromboembolism (VTE). Non-adherence to anticoagulation has been associated with increased frequency of VTE or stroke. This study evaluated 90 day persistence among patients prescribed rivaroxaban or warfarin for the treatment of acute VTE at an academic safety net hospital. We conducted a single center, retrospective cohort study of 314 consecutive patients newly prescribed rivaroxaban or warfarin for acute VTE between January 2016 and July 2017. Primary outcome was 90 day persistence, and secondary outcomes included 90 day readmission and/or ED visit, time to 90 m day readmission and/or ED visits, and attendance of direct oral anticoagulant education class. Of 314 patients, 78 were prescribed warfarin and 236 rivaroxaban. Patients had a mean age of 52 years, 62% were men, and 96% were diagnosed with deep vein thrombosis and/or pulmonary embolism. Persistence at 90 days was 52.6% among patients prescribed warfarin compared to 45.3% for patients prescribed rivaroxaban (p = 0.2678). Persistencewas associated with decreased 90 day hospital or ED readmission. Among patients prescribed rivaroxaban, attending a pharmacist led educational class was associated with a 2.5 fold increase in persistence (p < 0.0001). Among patients with new onset venous thromboembolism, 90 day persistence with anticoagulation was similarly low with either rivaroxaban or warfarin therapy. Participation in a pharmacist led DOAC class was associated with a 2.5-fold increase in persistence on rivaroxaban. [ABSTRACT FROM AUTHOR]

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet. [ABSTRACT FROM AUTHOR]

Introduction and objectives: In the perioperative setting, temporary interruption of direct oral anticoagulants (DOACs) is recommended. However, the safety of these recommendations is based on non-urological surgical experiences. Our objective was to verify the safety of these recommendations in patients undergoing radical prostatectomy (RP). Materials and methods: Patients regularly receiving a DOAC and scheduled for RP at our institution were prospectively assessed. DOAC intake was usually stopped 48 h before surgery without any preoperative bridging therapy. Postoperatively, patients received risk-adapted low-molecular weight heparin (LMWH). On the third day after unremarkable RP, DOAC intake was restarted and the administration of LMWH was stopped. We assessed perioperative outcomes and 30-day morbidity. Results: Thirty-two consecutive patients receiving DOAC underwent RP at our institution between 12/2017 and 07/2018. Time of surgery (median, 177 min) and intraoperative blood loss (median, 500 mL) were unremarkable. DOACs were restarted on the third postoperative day in 30 patients (94%). No patient had a significant hemoglobin level reduction after DOAC restart. Overall, 28% of patients experienced complications within 30 days after surgery. Most of which were minor (Clavien ≤ 2), three patients (9%), however, had Clavien ≥ 3 complications. Conclusion: Our report is the first to prospectively assess current guideline recommendations regarding DOAC restarting after major urological surgery. RP can safely be performed, if DOACs are correctly paused before surgery. Moreover, in case of an uneventful postoperative clinical course, DOACs can be safely restarted on the third postoperative day. A 9% Clavien ≥ 3 30-day morbidity warrants attention and should be further explored in future studies. [ABSTRACT FROM AUTHOR]

Purpose: To study whether polypharmacy or drug–drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin. Methods: We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied. Results: Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5–9 drugs, and 16% used ≥ 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0–4 vs 5–9 vs ≥ 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74–0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84–0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38–0.70) compared with warfarin. Conclusions: DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs. [ABSTRACT FROM AUTHOR]

Background: Although direct oral anticoagulants (DOAC) have proven at least equally effective in the prevention of acute ischemic stroke (AIS) in patients with atrial fibrillation as compared to the vitamin K antagonists (VKA), no reliable data on the severity of AIS of DOAC patients as compared to VKA is available. Methods: Using a prospectively collected cohort of AIS patients, we performed univariate and multivariate (displayed as adjusted Odds Ratios, OR and 95% confidence intervals, 95% CI) analyses regarding the severity of AIS in patients with preceding DOAC (N = 210) versus VKA (N = 173) therapy. Additionally, we provide a sensitivity analysis considering only patients with warranted therapeutic anticoagulation activity. Findings: In a comprehensive stroke center population, the frequency of AIS under DOAC was multiple times higher than previously reported at around 6% of all AIS and steadily increasing. National Institute of Health Stroke Scale (NIHSS) in VKA patients (median 7, IQR 2–14) was equal to DOAC (median 5, IQR 2–16) on univariate analysis (P = 0.229). According to the multivariable linear logistic regression analysis adjusting for confounders of severe stroke, VKA was not significantly associated with higher NIHSS scores (β − 0.165, 95% CI − 1.874 to 1.545, P = 0.850) as compared to DOAC. Also in the sensitivity analysis considering only patients with warranted therapeutic OAC therapy, VKA was not significantly associated with higher NIHSS scores (β − 1.392, 95% CI − 3.506 to 0.721, P = 0.195) as compared to DOAC. However, VKA as compared to DOAC was significantly associated with lower rates of good functional outcome at three months (0.527, 95% CI 0.300–0.928), but not with increased mortality (aOR 1.825, 95% CI 0.780–4.273). Interpretation: Ischemic stroke in patients taking DOAC is an important and frequent scenario. Stroke severity in our real world population dataset is equal in patients taking VKA and DOAC, also in the case of warranted anticoagulation therapy. Preceding VKA as compared to DOAC was associated with lower rates of good functional outcome without excess mortality, but a causal relationship cannot be proven by our study design. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this prospective comparative clinical study was to evaluate the effect of oral anticoagulants on peri- and post-operative bleeding during simple single tooth extractions, comparing patients in treatment with vitamin K antagonists (VKAs) and patients assuming direct oral anticoagulants (DOACs). Materials and methods: Patients under oral anticoagulant therapy needing dental extraction were eligible for entering the study; patients were enrolled following inclusion and exclusion criteria and divided into VKAs and DOAC group according to the anticoagulation therapy. Included patients underwent a simple single dental extraction with elevators and forceps with a maximum surgical time of 15 minutes, without anticoagulation therapy discontinuation. All participants were assessed pre-operatively, during surgery, 30 min minutes and 7 days after surgery. Biological complications were registered and post-extraction bleeding was clinically defined according to Iwabuchi classification. Parametric and non-parametric tests were used to evaluate the variables between the groups. Results: Sixty-five patients per group were enrolled and 130 teeth were extracted. The two groups were comparable for pre-, peri-, and post-operative variables. Only 1 patient of DOAC group and 2 patients for VKA group needed medical evaluation for post-extractive bleeding. No statistically significant difference resulted in post-operative bleeding events between the groups (p = 0.425). Conclusions: DOAC and VKA patients showed the same incidence of bleeding complications after simple single tooth extraction. Bleeding events were not statistically significant and not clinically relevant. Clinical relevance: Patients assuming DOACs can be treated similarly to patients in VKAs therapy with INR index between 2 and 3. Non-ceasing of DOAC therapy seems to be appropriate for simple single dental extractions. [ABSTRACT FROM AUTHOR]

Summary: Venous thrombosis and pulmonary embolism are common complications in patients with active cancer. For many years low molecular weight heparins (LMWH) have been the preferred treatment option for cancer patients, because of their superiority over vitamin K antagonists, which bear high risk of interaction and unsatisfactory anticoagulation. With the introduction of direct oral anticoagulants (DOAC) a second oral treatment option appeared. However, recommendations for the use of DOACs in the treatment of cancer-associated venous thromboembolic events were only given recently. DOAC possess a different side effect profile regarding drug/drug interactions. Recent publications revealed a slightly increased risk for non major bleedings compared to LMWH, and caution is advised when used in patients with gastrointestinal tract malignancies, especially upper gastro-intestinal tract malignancies. This review depicts actual considerations for anticoagulation in cancer patients to provide a rational for clinicians before treatment initiation. [ABSTRACT FROM AUTHOR]

Background Warfarin has been used in Japan for a long time in patients after cerebral embolism to prevent recurrence. Recently, several novel oral anti-coagulants (NOACs) have been approved for use and are gradually replacing warfarin. However, it remains unclear whether warfarin and other NOACs differ from each other with respect to drug costs and length of stay (LOS) during treatment in Japan. Objective To assess differences in LOS and direct medical cost between patients after cerebral embolism treated with warfarin and those treated with NOACs. Setting Thirteen acute care hospitals in Japan. Method For hospitalized patients with cerebral embolisms who were treated with NOACs and/or warfarin between April 2012 and March 2014, we assessed LOS for patients with warfarin and NOAC using log-rank test, and stratified proportional hazard regression. Also, we assess direct medical cost using paired-t test. Main Outcome measure LOS and medical cost after first treatment with warfarin and NOAC. Results The median LOS for NOACs-treated patients was 12.5 days and that for warfarin treated patients was 19.0 days while the corresponding mean medical costs were USD 7151 ± 6228 [JPY 736,546 ± 641,437] and USD 8950 ± 5891 [JPY 921,830 ± 606,765]. The drug cost for NOACs-treated patients was higher but costs for laboratory-test and hospitalization were lower than those for warfarin-treated patients. Conclusions For NOAC-treated patients, LOS was shorter, and medical cost during hospitalization tended to be lower than those for warfarin-treated patients, whereas NOACs prices were higher than warfarin price. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) have gradually entered the Czech market as alternatives to vitamin K antagonists and parenteral anticoagulants since 2008. Considering the eventual changes, the aim was to evaluate drug use and expenditure patterns on anticoagulants in the Czech Republic. A retrospective utilization study was conducted retrieving data from the State Institute for Drug Control database, including reports on drug supplies from distributors with anatomical therapeutic chemical classification (ATC) codes B01AA, B01AB, B01AE, B01AF, and B01AX. The utilization on national level was expressed as the ratio of the number of defined daily doses per 1000 inhabitants per day (DDD/TID). Expenditures on all anticoagulants were also assessed. Data was analyzed using PASW (version 18.0). Between January 2007 and December 2017, the national anticoagulant utilization rate increased continuously from 14.15 to 27.67 DDD/TID. The use of DOACs was 0.002 DDD/TID in 2008, increased to 6.04 DDD/TID in 2017. Warfarin utilization, after a small decrease in 2008, has shown nearly stable levels in the recent years (70.9% of all anticoagulants; mean 11.55 DDD/TID over the last 5 years), while its increase was halted by the spread of DOACs utilization (p < 0.05). In 2017, over half of the expenditures (51.1%) were due to oral anticoagulants, whereof 47.6% was related to DOACs. The results reflected a growing utilization and increasing costs of all anticoagulants, especially in DOACs at the expense of warfarin. Still, additional information regarding patient persistence and prescribing patterns is needed for a better understanding of oral anticoagulant utilization. [ABSTRACT FROM AUTHOR]

Stroke and venous thromboembolism continues to be a major cause of morbidity and mortality worldwide. The use of anticoagulation therapy has proven effective in the prevention of stroke and management of thromboembolism; however, initiating treatment may bear clinical burden given the capacity of these agents to cause bleeding. Originally, warfarin has been primarily used, but with the approval of direct oral anticoagulants, therapeutic recommendations have shifted to direct oral anticoagulants for first line therapy for venous thromboembolism for patients without cancer. As compared to warfarin, direct oral anticoagulants are associated with predictable pharmacokinetic profiles, lower bleeding risks, and minimal drug interactions. Complexities in the medication use process can however heighten the risks of causing adverse events. The purpose of this article is to describe common medication errors associated with direct oral anticoagulants, provide practical guidance on the management of direct oral anticoagulants, and suggest strategies to reduce errors. Efforts to minimize medication errors involve the participation of an interdisciplinary team that has standardized policies, risk reduction strategies, and guiding principles to achieve optimal therapeutic outcomes. Current primary literature is not robust in assessment of clinical impact of medication errors associated with DOACs but reports of adverse drug events have been noted. Future studies should be guided to assess clinical outcomes associated with medication errors and identify potential clinical interventions to optimize therapy. [ABSTRACT FROM AUTHOR]

Since their market approval, direct oral anticoagulants (DOACs) are being increasingly used for stroke prevention in patients with atrial fibrillation. However, the management of DOAC-treated patients with stroke poses several challenges for physicians in everyday clinical practice, both in the acute setting and in long-term care. This has spurred extensive research activity in the field over the past few years, which we review here. [ABSTRACT FROM AUTHOR]