Non-anticoagulated Patients Research Articles

Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context.

Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. To assess the impact of clinical context on anticoagulation and outcomes of SSPE. We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.

Decision of Anticoagulation in Nonvalvular Atrial Fibrillation in the Real World in the Non-Antivitamin K Anticoagulants Era.

Background. Patients with nonvalvular atrial fibrillation (NVAF) have five times higher risk of stroke than the general population. Anticoagulation (ACO) in NVAF is a class I indication after assessing the CHA2DS2-VASc and HAS-BLED scores. However, in the real world, NVAF patients receive less ACO than needed due to patients’ comorbidities that can be assessed by the Charlson comorbidity index (CCI). The use of non-antivitamin K anticoagulants (NOAC) has improved the decision to anticoagulate. Objective. We analyzed the factors influencing the ACO prescribing decision in NVAF patients in the real world and the changes induced by the introduction of NOAC. Method. We carried out an observational retrospective cross-sectional study that included consecutive patients with permanent NVAF and CHA2DS2-VASc ≥ 2, admitted to a community hospital between 2010–2011 (group 1, 286 patients), when only vitamin K antagonists (VKA) were used, and 2018–2019 (group 2, 433 patients), respectively. We calculated CHA2DS2-VASc, HAS-BLED, and CCI and recorded the ACO decision and the use of VKA or NOAC in group 2. We compared the calculated scores between ACO and non-anticoagulated (nonACO) patients in both groups and between groups. Results. A 31.5% share of patients in group 1 and 12.9% in group 2 did not receive ACO despite a CHA2DS2-VASc score ≥ 2. In group 1, nonACO patients had higher HAS-BLED and CCI scores than the ACO patients, but their CHA2DS2-VASc scores were not significantly different. Old age, dementia, severe chronic kidney disease, neoplasia, and anemia were the most frequent reasons not to prescribe anticoagulants. In group 2, more nonACO patients had dementia, diabetes mellitus, and higher HAS-BLED than ACO patients. Moderate-severe CKD, neoplasia with metastasis, liver disease, anemia, and diabetes mellitus were statistically significantly more frequent in nonACO patients from group 1 than those from group 2. In group 2, 55.7% of ACO patients received NOAC. Conclusions. In real-world clinical practice, the decision for anticoagulation in NVAF is influenced by patient age, comorbidities, and risk of bleeding, and many patients do not receive anticoagulants despite a high CHA2DS2-VASc score. The use of NOAC in the past few years has improved treatment decisions. At the same time, the correct diagnosis, treatment, and surveillance of comorbidities have cut down the risk of bleeding and allowed anticoagulant use according to guidelines.

The non-vitamin K antagonist oral anticoagulants and heparin-induced prolongation of the activated coagulation time

Background and aimsUnfractionated-heparin (UFH) is the first-choice parenteral anticoagulant during invasive percutaneous procedures and its effect is monitored by the activated coagulation time (ACT). The effects of the non-vitamin K antagonist oral anticoagulants (NOACs) on the ACT and on ACT prolongation by UFH were not clearly established. We assessed the ACT prolongation induced by different UFH concentrations in blood samples of patients taking the four types of currently marketed NOACs and in patients not taking anticoagulants. Methods and resultsWe measured the ACT in patients on dabigatran 110 mg (n = 8), rivaroxaban (n = 10), apixaban (n = 9) and edoxaban (n = 10) at supposed peak plasma concentrations, before and after in vitro addition of 3 UFH concentrations, corresponding to doses of 2000, 5000 and 10,000 IU. Seven non-anticoagulated patients served as controls.Patients in the 5 groups did not differ significantly for age, body weight and glomerular filtration rate. Baseline ACTs (s, mean ± SD) were 192 ± 27, 124 ± 14, 132 ± 14, 151 ± 30 and 134 ± 7 in dabigatran 110, rivaroxaban, apixaban, edoxaban and controls, respectively (P < 0.05 for dabigatran vs the other NOACs). We found a linear prolongation of the ACT with the in vitro UFH addition (P < 0.001), but prolongation was similar between the NOACs and controls. ConclusionsDabigatran induces a moderate, significant ACT prolongation. None of the NOACs affects the UFH-induced ACT prolongation in the commonly used UFH range. The dose of UFH currently recommended to achieve the target ACT should thus be used irrespective of whether patients are taking NOACs or not.

Correlation between Thrombin Generation, Standard Coagulation Assays, and Viscoelastic Assays for Hemostatic Assessment in Critically Ill Children.

Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is commonly used in hemostasis research laboratories. Our objective was to determine the correlation of clinically available hemostasis assays with TG in critically ill children. Children (<18 years old, >3 kg in weight) in the intensive care unit were enrolled from March 2016 to December 2019 in a prospective 2-center study. Coagulation tests were prothrombin time, activated thromboplastin time, anti-Xa assay, viscoelastic assays (thromboelastography [TEG], rotational thromboelastometry [ROTEM]), and TG (induced by 20 pM tissue factor in platelet poor plasma and reported as endogenous thrombin potential [ETP; nM*min]). Data are reported as median (interquartile range) or Spearman coefficient (ρ). Patients (n = 106, age 10.2 years [3.8-15.3]) were divided into 3 groups: (a) no anticoagulation (n = 46), (b) anticoagulation (unfractionated heparin) without extracorporeal life support (n = 34), or (c) with extracorporeal life support (n = 26). ETP was decreased in anticoagulated compared to non-anticoagulated patients (group 1: 902.4 [560.8-1234], group 2: 315.6 [0.0-962.2], group 3: 258.5 [0.0-716.6]; P < 0.0001). Across all patients, ETP correlated best with TEG kinetic time (TEG-K), in min (ρ = -0.639), followed by TEG reaction time, in min (ρ = -0.596). By group, ETP correlated best with international normalized ratio for group 1 (ρ = -0.469), TEG-K time for group 2 (ρ = -0.640), and anti-Xa for group 3 (ρ = -0.793). Standard and viscoelastic assays have varying correlation with TG in critically ill children. TEG-K time had the most consistent moderate correlation with ETP across all groups.

Delayed Surgery Does Not Reduce Transfusion Rates in Low-Energy Hip Fractures on Direct Oral Anticoagulants.

To compare transfusion rates in patients on direct oral anticoagulants (DOACs) with nonanticoagulated patients undergoing hip fracture surgery and, secondarily, to determine whether time to surgery or complications differ between these groups. Multicenter retrospective cohort. Three tertiary care, academic, Level I trauma centers. Acute, operatively treated, low-energy hip fracture patients 55 years of age and older were included. Anticoagulated patients were matched in a 1:2 ratio to "control" nonanticoagulated hip fracture patients using propensity score matching. The primary outcome was incidence of perioperative transfusion. The secondary outcomes included time to surgery, length of stay, and 90-day complications, readmissions, reoperations, and mortality. One hundred thirty-two patients with hip fracture admitted on DOACs were identified (107 factor Xa inhibitors, 25 dabigatran) and were matched to 262 "control" nonanticoagulated patients. There was no difference in overall transfusion rates between anticoagulation and control groups (43.2%; n = 57 DOAC vs. 39.7%; n = 104 control; P = 0.517). The median time from admission to surgery was 41.7 hours in the DOAC group and 26.0 hours in the control group (P < 0.001). There were no differences in 90-day complication, readmission, reoperation, or mortality rates between DOAC and control groups. Comparing DOAC patients undergoing surgery within 24 hours and after 24 hours, there were no differences in transfusion rates (P = 0.558) or overall complication rates (P = 0.179). This study supports growing evidence that DOAC use should not be a determining factor in delaying surgery for patients with hip fracture who are otherwise medically optimized. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Effect of Anticoagulation on the Treatment of Dupuytren Contracture with Collagenase.

There have been no formal studies of the use of collagenase clostridium histolyticum (Xiaflex; Endo Pharmaceuticals, Malvern, Pa.) in the anticoagulated patient. Previous study on its use excluded patients receiving anticoagulation therapy. This study reviewed the effects of anticoagulation use in patients undergoing collagenase clostridium histolyticum injection and cord rupture to determine safety and efficacy. The authors retrospectively reviewed patients receiving collagenase clostridium histolyticum injections for Dupuytren contracture between 2010 and 2017. Outcomes included type of anticoagulation, skin tear, tendon rupture, lymphadenopathy, sensory abnormality, hematoma, and bleeding. A total of 388 injections were performed in 197 patients. The average clinical follow-up was 311 days. Fifty-two percent of patients (n = 201) were anticoagulated. The vast majority were taking aspirin (acetylsalicylic acid) (n = 182), followed by warfarin (n = 27), clopidogrel (n = 9), apixaban (n = 8), rivaroxaban (n = 4), and dabigatran (n = 2). There were 42 skin tears, 21 in the anticoagulated group. One tendon rupture occurred in the anticoagulated group (acetylsalicylic acid) and none occurred in the nonanticoagulated group (p = 0.34). No patients experienced sensory abnormalities, a hematoma requiring intervention, or uncontrollable bleeding. Anticoagulation is commonly encountered by hand surgeons treating Dupuytren contracture. There is no significant difference in complications in the anticoagulated patient versus the nonanticoagulated patient. It is safe to perform collagenase clostridium histolyticum injections for Dupuytren contracture in the anticoagulated patient, regardless of the type of anticoagulation. Therapeutic, III.

Effect of Direct Oral Anticoagulants on Treatment of Geriatric Hip Fracture Patients: An Analysis of 15,099 Patients of the AltersTraumaRegister DGU®.

Background and Objectives: The increased use of direct oral anticoagulants (DOACs) results in an increased prevalence of DOAC treatment in hip fractures patients. However, the impact of DOAC treatment on perioperative management of hip fracture patients is limited. In this study, we describe the prevalence of DOAC treatment in a population of hip fracture patients and compare these patients with patients taking vitamin K antagonists (VKA) and patients not taking anticoagulants. Materials and Methods: This study is a retrospective analysis from the Registry for Geriatric Trauma (ATR-DGU). The data were collected prospectively from patients with proximal femur fractures treated between January 2016 and December 2018. Among other factors, anticoagulation was surveyed. The primary outcome parameter was time-to-surgery. Further parameters were: type of anesthesia, surgical complications, soft tissue complications, length of stay and mortality. Results: In total, 11% (n = 1595) of patients took DOACs at the time of fracture, whereas 9.2% (n = 1325) were on VKA therapy. During the study period, there was a shift from VKA to DOACs. The time-to-surgery of patients on DOACs and of patients on VKA was longer compared to patients who did not take any anticoagulation. No significant differences with regard to complications, type of anesthesia and mortality were found between patients on DOACs compared to VKA treatment. Conclusion: An increased time-to-surgery in patients taking DOACs and taking VKA compared to non-anticoagulated patients was found. This underlines the need for standardized multi-disciplinary orthopedic, hematologic and ortho-geriatric algorithms for the management of hip fracture patients under DOAC treatment. In addition, no significant differences regarding complications and mortality were found between DOAC and VKA users. This demonstrates that even in the absence of widely available antidotes, the safe management of geriatric patients under DOACs with proximal femur fractures is possible.

Time-to-Incision for Hip Fractures in a Canadian Level-1 Trauma Centre: Are We Respecting the Guidelines?

BackgroundSurgical intervention within 48 hours is recommended for hip fractures in the elderly in order to reduce post-operative complications and lower mortality rates. The purpose of this retrospective study is to explore the causes of surgical delays for acute geriatric hip fractures.MethodsThis is a retrospective cohort study involving a total of 109 consecutive geriatric patients who sustained proximal femur fractures (“hip fractures”), who subsequently underwent definitive fixation. Clinical, demographic, and direct costing data were extracted via a modern system and electronic medical records on a centralized data warehouse. Surgical delays and length of stay were analyzed according to clinical variables.ResultsThe established benchmark of a time-to-surgery of less than 48 hours was respected for 63 (57.8%) patients. Patients on oral anticoagulant (ACO) waited significantly longer, on average 58 hours compared to 44 for non-anticoagulated patients (p = .007). Patients with higher ASA scores waited significantly longer (p = .0018). More importantly, patients treated within 48 hours were discharged significantly earlier, on average after 10 days compared to 16 days for patients who waited more than 48 hours before receiving surgical treatment (p = .003), regardless of the pre-operative waiting time.ConclusionFewer than 60% of patients received surgery within the 48-hour benchmark after being admitted for an acute hip fracture in a Level-1 trauma centre. Patients with more comorbidities waited longer and stayed longer in the hospital after surgery. Implementing strategic, evidence-based changes should be done using this data to improve care of this vulnerable population.

Abstract TP193: Atrial Fibrillation Burden Is Not Associated With Recurrent Cerebrovascular Events In Anticoagulated Stroke Patients: An Arest Trial Sub-study

Introduction: The burden of Atrial Fibrillation (AF) has previously been associated with a higher stroke risk in non-anticoagulated patients. We aim to find whether there is also an association between AF burden and recurrent cerebrovascular events in anticoagulated AF patients after their initial acute ischemic stroke (AIS) or transient ischemic attacks (TIA). Methods: The AREST study (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was a multi-center, randomized controlled trial of early apixaban versus warfarin at one week post-TIA or two weeks post-AIS, in AF patients from 2015 to 2019. Subjects received either 30-day continuous electrocardiographic monitoring or an implantable device (i.e., pacemaker, loop recorder, or defibrillator). Logistic regression and Kendall's tau-b test were utilized to identify an association between AF burden and the proportion of subjects who developed recurrent cerebrovascular events. Results: Of 91 subjects enrolled into AREST, heart rhythm monitoring was assessed in 49 (54%); over half (59%) clustered at the extreme ends of the distribution, at either low (≤1%) or high (≥99%) AF burden. Higher AF burden was not significantly correlated with an increased risk of recurrent stroke or TIA (Odds Ratio = 0.99 [95% confidence interval (CI), 0.98-1.0]; p=0.518). Moreover, there was no statistically significant association between AF burden and the composite outcomes after adjusting for either apixaban or warfarin. Conclusions: AF Burden was not found to be associated with recurrent cerebrovascular events in patients taking oral anticoagulant after an AIS or TIA. Further research is needed to confirm these findings.

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

BackgroundDOAC Filter (DF) is a new device to overcome interference in lupus anticoagulant (LAC) testing by direct oral anticoagulants (DOACs). ObjectivesWe evaluated DOAC removal from plasma and elimination of DOAC interference in LAC testing by DF, and impact of DF on LAC assays in a representative patient cohort, including a comparison with DOAC‐Stop (DS). MethodsNormal pooled plasma (NPP) was spiked with increasing concentrations of apixaban, rivaroxaban, edoxaban, and dabigatran. DOAC and LAC was measured on untreated, DF‐treated, and DS‐treated spiked samples. Coagulation parameters and thrombin generation were measured on patient samples (n = 20) before and after DF. Patients treated with DOAC, vitamin K antagonist, or heparin and nonanticoagulated patient samples (n = 139) were tested for LAC before and after DF. ResultsIn spiked NPP, levels were below the lower limit of quantification (LLoQ) after DF/DS treatment for all DOAC concentrations. Following DF, levels were below LLoQ for 53 of 56 DOAC‐containing patient samples. Twenty‐eight of 33 LAC‐positive DOAC‐containing samples became negative after filtration, whereas 5 remained LAC‐positive (1/5 from a patient with antiphospholipid syndrome [APS]). Four LAC‐positive DOAC‐containing samples (from patients without APS), became negative after filtration, whereas they remained LAC positive after DS. In the non‐DOAC patient groups following DF, LAC changed from positive to negative in 8 (due to a procoagulant effect) and vice versa in 2 cases. ConclusionDF reduces DOAC interference in LAC testing. As incomplete DOAC removal may occur, DOAC measurements should be performed after filtration. A procoagulant effect after filtration may lead to erroneous LAC results in non–DOAC‐containing samples. Therefore, using DF should be restricted to DOAC‐containing samples.

The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study

IntroductionAnticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. Materials and methodsThis was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. ResultsWe studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%–31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%–33.5%) without anticoagulation (absolute risk difference [ARD], −2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%–20.2%) with anticoagulation and 20.9% (95% CI 19.7%–22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). ConclusionsAmong outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.

Direct oral anticoagulants are associated with potentially bleeding lesions in suspected mid-gastrointestinal bleeding

Background and aim Direct oral anticoagulants (DOACs) became a widespread alternative in anticoagulant therapy. Nevertheless, concerns are raised about their safety, with increased gastrointestinal bleeding rates being described. There are scarce studies regarding DOACs effect on small-bowel capsule endoscopy (SBCE) findings. We aimed to assess if the detection of lesions with high bleeding potential on SBCE was significantly different in patients treated with DOACs when compared to non-anticoagulated patients and to patients anticoagulated with other agents. Methods Cohort study including consecutive patients who underwent SBCE for suspected mid-gastrointestinal bleeding (MGIB) in 2019 and 2020. Results From 148 patients, 38 (25.7%) were anticoagulated, of which 26 (68.4%) with DOACs. P2 lesions were detected in 36.5% (n = 54) of the patients. These lesions were more frequently detected in patients under DOACs treatment when compared to non-anticoagulated patients (69.2% vs. 29.1%; p=.001), and also when compared to patients treated with other anticoagulants (69.2% vs. 33.3%; p=.037). No differences in P2 lesions detection were observed between patients treated with other anticoagulants and non-anticoagulated patients (33.3% vs. 29.1%; p=.747). In multivariate analysis, DOACs usage was significantly associated with higher detection rates of P2 lesions on SBCE, when adjusted for classical risk factors for MGIB (OR: 3.38; 95%CI = 1.23–9.26; p=.018). Conclusions Despite their undeniable cardiovascular benefits and easy applicability, DOACs should still be considered with caution. These drugs were significantly associated with higher risk of potentially bleeding lesions on SBCE when compared to other anticoagulants and represent an independent risk factor for MGIB when adjusted for other variables.

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

BackgroundLupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin‐activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI). ObjectivesValidate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study. Patients/MethodsSix centers from four countries analyzed samples with TSVT/ET from 81 nonanticoagulated patients with LA, patients with established antiphospholipid syndrome (APS), and proven persistent LA who were either not anticoagulated (n = 120) or were anticoagulated with VKAs (n = 180) or DFXaIs (n = 71). Additionally, 339 nonanticoagulated LA‐negative patients, and 575 anticoagulated non‐APS patients (172 VKA, 403 DFXaI) were tested. Anticoagulant spiking experiments were performed and 112 samples containing potential interferences (i.e., direct thrombin inhibitors) were tested. Results were evaluated against locally derived cutoffs. Imprecision was evaluated. ResultsCutoffs were remarkably similar despite use of different analyzers and donor populations. Cutoffs for TSVT ratio, ET ratio, percent correction, and normalized TSVT ratio/ET ratio ranged between 1.08 and 1.10, 1.09 and 1.12, 9.3% and 14.8%, and 1.10 and 1.15, respectively. Coefficients of variation for TSVT and ET ratios were ≤5.0%. TSVT/ET exhibited sensitivity, specificity, and negative and positive predictive values of 78.2%/95.0%/86.3%/91.5%, respectively, with established APS as the LA‐positive population, and 86.9%/95.0%/76.8%/97.4%, respectively, with triple‐positive APS. Interference was seen with direct thrombin inhibitors, unfractionated heparin, and low molecular weight heparins, but not VKAs or DFXaIs. ConclusionsTSVT/ET are validated for LA detection in nonanticoagulated patients and those on VKAs or DFXaIs.

Retrospective Study of 1255 Non-Anticoagulated Patients with Nonvalvular Atrial Fibrillation to Determine the Risk of Ischemic Stroke Associated with Left Atrial Spontaneous Echo Contrast on Transesophageal Echocardiography

BackgroundLeft atrial spontaneous echo contrast (LASEC) is associated with an increased risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). Therefore, a tool that identifies the risk of LASEC in non-anticoagulated patients with NVAF may be helpful for stroke risk stratification and early stroke prevention in these patients. The aim of this retrospective study was to establish a novel risk score model to determine the risk of ischemic stroke associated with LASEC on transesophageal echocardiography (TEE).Material/MethodsThis study retrospectively and consecutively enrolled 1255 non-anticoagulated patients with NVAF who underwent TEE prior to catheter ablation or left atrial appendage occlusion. Most importantly, a novel nomogram was developed using a logistic regression model to predict the risk of LASEC.ResultsA nomogram was established for LASEC prediction which included 5 independent risk factors determined by multivariable logistic regression analysis: increased age, non-paroxysmal atrial fibrillation, previous stroke/transient ischemic attack, congestive heart failure, and left atrial enlargement. The receiver operating characteristic curve analysis showed that the area under the curve (AUC) of the novel risk score model was 0.879 (95% confidence interval: 0.849–0.909, P<0.001). Compared with the CHA2DS2-VASc score, the novel risk score model had a better predictive power (AUC: 0.879 vs 0.617, P<0.001).ConclusionsThis novel risk score model effectively predicted the presence of LASEC in non-anticoagulated patients with NVAF.

Abstract 10623: Validation of Embolic and Bleeding Risk Scores in Patients with Atrial Fibrillation and Cancer

Introduction: Atrial fibrillation (AF) is common among cancer patients. Anticoagulation can reduce the risk of stroke and systemic embolism in AF patients. However, anticoagulation in patients with cancer can be difficult given unpredictable changes in thrombosis and bleeding risk. Although CHA 2 DS 2 -VASc and HAS-BLED are useful, their predictive performance in patients with cancer is unknown. Hypothesis: CHA 2 DS 2 -VASc and HAS-BLED scores in AF patients with cancer could lead to misclassification. Methods: Overall, 16,056 AF patients between 2014 and 2018 were followed during a median follow-up of 4.9 years, including 1,137 with cancer history. We used C statistic and Brier score for assessing the performance of both scores. Results: Discrimination, assessed with C statistics (assuming death as a competing risk), was similar between cancer and non-cancer anticoagulated patients. However, in non-anticoagulated patients, c-statistic of CHA 2 DS 2 -VASc was poor and significantly lower in non-cancer patients. The overall precision of the CHA 2 DS 2 -VASc score was good throughout the follow-up (Brier score &lt;0.1), both in patients with and without cancer history. Regarding to HAS-BLED score, calibration and discrimination were poor in cancer patients, although without significant differences in comparison with non-cancer patients. In non-anticoagulated cancer patients and in those with active cancer, the embolic risk of CHA 2 DS 2 -VASc score = 1 was similar to CHA 2 DS 2 -VASc score ≥ 2. Only AF patients with cancer and CHA 2 DS 2 -VASc score = 0 presented a truly low risk of embolic events (negative predictive value 100%). A HAS-BLED score &gt; 3 did not identify AF patients with cancer at higher bleeding risk. Conclusions: In AF patients with cancer, neither the CHA2DS2-VASC score nor the HASBLED score were useful for predicting embolic and hemorrhagic events, respectively. However, a CHA 2 DS 2 -VASc score 0 is useful to identify low embolic risk patients with AF and cancer.

Relative Interfering Effects of In Vivo Direct Oral Anticoagulants on Routine Coagulation Tests

Background:The interfering effects of DOACs on the screening coagulation tests, such as prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen assay, have been shown mainly by in vitro spiking experiments. However, the effects of DOACs on coagulation tests in real-world samples from anticoagulated patients are unknown because of the difficulty in selectively eliminating DOAC from blood samples already containing DOACs.Method:Citrated blood samples were drawn from patients on anticoagulation therapy (rivaroxaban and edoxaban). In addition, blood samples from patients not on anticoagulation were collected. PT INR and APTT were measured from those samples by coagulometers from two manufacturers (Roche t711, Swiss and ACL-TOP, USA). We also measured DOAC levels from the same samples by anti-FXa activity (Hyphen Biomed, France). Then, we compared the test results in relation to the DOAC levels.Results:The PT INR, APTT, and fibrinogen assay results from non-anticoagulated patients measured by the two coagulometers were comparable (PT INR: y = -3.353 + 1.029 x; APTT: y = -6.276 + 1.101x; fibrinogen: y = -3.353 + 1.029 x; Passing Bablok). We included blood samples from 61 patients on rivaroxaban and 75 patients on edoxaban. From the rivaroxaban samples we observed the regression line change for PT INR (y = 0.6303 + 0.3712x) and for APTT (y = -10.71+1.358x). The comparability of fibrinogen assay was not affected significantly (y = -17.39+1.01x). From the edoxaban samples we also observed the similar change of the regression line (PT INR: y = 0.4728 + 0.5661x; APTT: y = -133.07+2.014x). Fibrinogen levels were comparable (y = -28.95+1.082x).Conclusion:The susceptibility of screening coagulation tests to the interfering effects of in vivo DOAC is dependent on the reagents and coagulometers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Are low doses of non-vitamin K antagonists effective in Chinese patients with atrial fibrillation? A report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry.

Suboptimal low dosages of non-vitamin K antagonist oral anticoagulants (NOACs) are often inappropriately used due to a fear of bleeding, particularly among elderly patients. Such practice is common in Asia, and we aimed to evaluate the use of low-dose NOACs and their impact on clinical outcomes among Chinese patients with atrial fibrillation. The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry was a prospective, multicenter study conducted in China from October 2014 to December 2018. For this report, we included NOAC-treated patients with available data on NOAC dosage and one-year follow-up. Logistic regression analysis assessed the association (adjusted for age, sex, prior ischemic stroke, prior major bleeding, heart failure, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, liver disease, current anemia) between the low doses and study outcomes among NOAC-treated patients, as well as comparisons with non-anticoagulated patients. The eligible cohort included 1310 NOAC-treated patients (mean age of 72.1 ± 10.9; 38.9% female), of whom 341 (26.0%) received a low "off-label" dose. The use of low-dose NOACs was independently associated with higher odds of the composite outcome (OR: 2.51; 95% CI: 1.11-5.71) and thromboembolism (OR: 4.73; 95% CI: 1.11-20.01). Compared with non-anticoagulated patients, lower rates of the composite outcome (7.3% vs. 11.3%; p = 0.025) and all-cause death (5.3% vs. 9.7%; p = 0.007) were seen in the low-dose group (ORs 0.50; 95% CI: 0.32-0.78, and 0.42; 95% CI: 0.26-0.70, respectively). Low doses of NOACs should not be recommended as a part of standard therapy among Chinese patients with atrial fibrillation as their use was associated with a higher odds ratio of the composite outcome and thromboembolic events compared with standard dose NOAC regimens. Compared to non-treatment, the use of low-dose NOAC may result in a survival benefit (but not thromboembolic reduction) among high-risk patients.

Impact of prior history of cancer in the outcomes of patients with atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is common among cancer survivors, but anticoagulant therapy in is particularly challenging in this population. Aim We analyzed how a previous diagnosis of cancer influences the embolic and hemorrhagic risk in AF patients in order to guide anticoagulant therapies. Methods We used a large retrospective and observational cohort of AF patients from Vigo, Spain (2014–2018). Primary endpoint were embolic and haemorrhagic events during follow-up. Secondary endpoints were all cause mortality, CV mortality, acute myocardial infarction (AMI) and heart failure (HF) admission. Results From the 16,056 included patients, 7.1% had a current/past diagnosis of cancer. Median follow-up was 4.9 years. The rate of anticoagulation therapy was similar in cancer and non-cancer patients (74.8% vs 75.8) although there was a higher prescription of heparin and a lower prescription of VKA in cancer group. Cancer patients had a higher embolic (CHA2DS2-VASC 3.5±1.5 vs 3.2±1.5; p&amp;lt;.001) and hemorrhagic risk (HASBLED 3.0±1.2 vs 2.6±1.2; p&amp;lt;.001). Embolic and hemorrhagic risk stratification with CHA2DS2-VASC and HASBLED scores was only accurate in patients with past (non-active) cancer (sHR CHA2DS2-VASC for embolic events: 1.26, 95% CI 1.02–1.54, P=.028 and sHR HASBLED for bleeding events 1.11, 95% CI 1.01–1.23, P=.029) but not in active-cancer patients (CHADS2-VASC sHR 1.14, 95% CI 0.98–1.32; p=.076 and HASBLED sHR 1.08, 95% CI 0.99–1.17; p=.070). After adjusting by age, sex, CHA2DS2-VASC, HASBLED, and anticoagulation therapy, cancer was not associated with higher risk of embolic events (sHR 0.73, 95% CI 0.41–1.26; p=.256), neither in anticoagulated nor in non-anticoagulated patients. However, cancer patients presented a higher bleeding risk (sHR 1.18, 95% CI 1.07–1.30; p=0.001), both in anticoagulated and non-anticoagulated patients. Anticoagulation therapy was associated with lower rate of embolic events and with higher rate of bleeding events in both groups of patients with and without cancer, although the embolic-hemorrhagic balance associated with anticoagulation was more favorable in cancer patients (for each avoided embolism with anticoagulation, 5.7 bleeding and 11.7 bleeding episodes occurred in cancer and non-cancer group respectively). We found no association between cancer and AMI or CV mortality rates. All-cause mortality was higher in cancer patients. For HF, only chemotherapy-treated patients presented higher risk (sHR1.54, 95% CI 1.10–2.16; p=0.012). Conclusion Patients with prior history of cancer have higher bleeding risk but similar embolic risk compared to patients without cancer history. Anticoagulation significantly reduced embolic events, with an increase in bleeding outcomes. However, the embolic-hemorrhagic profile of anticoagulation was more favorable in patients with cancer than without it. Funding Acknowledgement Type of funding sources: None. Scores performances by cancer activityEmbolic/bleeding net clinical balance

Do oral anticoagulants impact outcomes and false lumen patency after repair of acute type A aortic dissection?

ObjectiveThe study objective was to analyze the effects of chronic oral anticoagulation on long-term outcomes after repair of type A acute aortic dissection and its influence on false lumen fate. MethodsWe studied 188 patients (median age, 62 years; 74% were male) who underwent repair of type A aortic dissection; patients receiving postoperative chronic oral anticoagulation (n = 59) were compared with those receiving antiplatelet therapy alone (n = 129). ResultsMedian age was similar: 60 years (18-79 years; OAC group) versus 64 years (22-86; no-OAC group) (P = .11); patients taking anticoagulants were more frequently male (88% vs 67%, P = .003). After a median follow-up of 8.4 years (2 months to 30 years), 58 patients died, 18 of aortic-related causes, and 37 patients underwent aortic reintervention. After multivariable adjustment, anticoagulation showed no significant effect on long-term survival (hazard ratio, 0.85; 95% confidence interval, 0.41-1.76; P = .66) or risk of reintervention (hazard ratio, 0.55; 95% confidence interval, 0.27-1.15; P = .11). Analysis of 127 postoperative computed tomography scans showed a patent false lumen in 53% of anticoagulated patients versus 38% of nonanticoagulated patients (P = .09): partially thrombosed in 8% versus 28% (P = .01) and thrombosed in 39% versus 34% (P = .63), respectively. In patients with a control computed tomography, there were 6 late aortic-related deaths, 1 among anticoagulated patients and 5 in those who were not. ConclusionsChronic anticoagulation after repair of type A acute aortic dissection favors persistent late false lumen patency, which is not a risk factor for late mortality or reoperation. Chronic anticoagulation can be administered safely to patients with repaired type A acute aortic dissection regardless of its specific indication.

Early anticoagulation in atrial fibrillation-related acute ischaemic stroke: efficacy and safety profile.

To evaluate the effects of early anticoagulation on functional outcome, recurrent ischaemic events and haemorrhagic complications in Atrial Fibrillation (AF)-related acute ischaemic strokes (AIS). We retrospectively evaluated patients hospitalised in a Stroke Unit due to AF-related AIS. Patients were divided according to anticoagulation initiation timing (0-4days, 5-14days, no anticoagulation by the 14th day). We assessed the following outcomes at 3 months: favourable functional outcome [modified Rankin Scale (mRS) score 0-2 or equal to pre-stroke], recurrent ischaemic events and haemorrhagic complications after anticoagulation initiation. We included 395 patients. Anticoagulation was initiated at days 0-4 in 33.9% of patients, days 5-14 in 25.3% and not initiated by the day 14 in 40.8%. Factors associated with earlier anticoagulation included lower previous mRS, valvular AF and lower stroke severity. Favourable functional outcome occurred in 40.2% of patients, with lower odds in those anticoagulated at 5-14 versus 0-4days (OR: 0.47, 95% CI: 0.23-0.94), independently of age, previous mRS and stroke severity. Recurrent ischaemic events occurred in 8.3% of patients, with higher odds in non-anticoagulated patients by the 14th day, compared to the remainder groups (OR: 3.26, 95% CI: 1.29-8.22 vs. 0-4days and OR: 8.16, 95% CI: 1.76-37.9 vs. 5-14days). In patients who started anticoagulation (n = 288), haemorrhagic complications occurred in 10.8%, being more frequent in those who started at 0-4days vs. > 14days. However, it did not abolish the 0-4-day initiation's benefit on functional outcome. Early anticoagulation was associated with lower ischaemic recurrence and better functional outcome at 3 months. Additional studies are needed to better clarify its haemorrhagic risk.