Timing of Anticoagulation Resumption and Risk of Ischemic and Hemorrhagic Complications in Patients With ICH and Mechanical Heart Valves.

BACKGROUND AND OBJECTIVES: In patients with mechanical heart valves and recent intracranial hemorrhage (ICH), clinicians need to balance the risk of thromboembolism during the period off anticoagulation and the risk of hematoma expansion on anticoagulation. The optimal timing of anticoagulation resumption is unknown. We aimed to investigate the relationship between reversal therapy and ischemic stroke, between duration off anticoagulation and risk of ischemic strokes or systemic embolism and between timing of anticoagulation resumption and risk of rebleeding and ICH expansion. METHODS: We conducted a retrospective cohort observational study in 3 tertiary hospitals. Consecutive adult patients with mechanical heart valves admitted for ICH between January 1, 2000, and July 13, 2022, were included. The primary end points of our study were thromboembolic events (cerebral, retinal, or systemic) while off anticoagulation and ICH expansion after anticoagulation resumption (defined by the following criteria: increase by one-third in intracerebral hematoma volume, increase by one-third in convexity subdural hemorrhage diameter, or visually unequivocal expansion of other ICH locations to the naked eye). RESULTS: A total of 171 patients with mechanical heart valves who experienced ICH were included in the final analysis. Most of the patients (79.5%) received reversal therapy for anticoagulation. Patients who received anticoagulation reversal therapy did not have increased risk of thromboembolic complications. Time off anticoagulation was not associated with risk of ischemic stroke; only 2 patients had a stroke within 7 days of the ICH, and both had additional major risk factors of thromboembolism. The rate of ischemic stroke/transient ischemic attack while off anticoagulation was lower than the rate of ICH expansion once anticoagulation was resumed (6.4% vs 9.9%). Furthermore, patients who developed ICH expansion had higher mortality compared with patients who had ischemic stroke while being off anticoagulation (41% vs 9%). Use of intravenous heparin bridging upon resumption of warfarin was strongly associated with increased risk of ICH expansion as compared with restarting warfarin without a heparin bridge. DISCUSSION: Withholding anticoagulation for at least 7 days after ICH may be safe in patients with mechanical heart valves. Heparin bridging during anticoagulation resumption may be associated with increased risk of bleeding.

Histon activities in the extracellular environment: regulation and prothrombotic implications.

PURPOSE OF REVIEW: Thromboembolic complications are a major contributor to global mortality. The relationship between inflammation and coagulation pathways has become an emerging research topic where the role of the innate immune response, and specifically neutrophils in "immunothrombosis" are receiving much attention. This review aims to dissect the intricate interplay between histones (from neutrophils or cellular damage) and the haemostatic pathway, and to explore mechanisms that may counteract the potentially procoagulant effects of those histones that have escaped their nuclear localization. RECENT FINDINGS: Extracellular histones exert procoagulant effects via endothelial damage, platelet activation, and direct interaction with coagulation proteins. Neutralization of histone activities can be achieved by complexation with physiological molecules, through pharmacological compounds, or via proteolytic degradation. Details of neutralization of extracellular histones are still being studied. SUMMARY: Leveraging the understanding of extracellular histone neutralization will pave the way for development of novel pharmacological interventions to treat and prevent complications, including thromboembolism, in patients in whom extracellular histones contribute to their overall clinical status.

Extremity fractures, attempted suicide, blood transfusion and thromboembolic events are independent risk factors for a prolonged hospital stay in severely injured elderly.

METHODS: Due to demographic change, the number of polytraumatized geriatric patients (> 64 years) is expected to further increase in the coming years. In addition to the particularities of the accident and the associated injury patterns, prolonged inpatient stays are regularly observed in this group. The aim of the evaluation is to identify further factors that cause prolonged inpatient stays. A study of the data from the TraumaRegister DGU® from 2016-2020 was performed. Inclusion criteria were an age of over 64 years, intensive care treatment in the GAS-region, and an Injury Severity Score (ISS) of at least 16 points. All patients who were above the 80th percentile for the average length of stay or average intensive care stay of the study population were defined as so-called long-stay patients. This resulted in a prolonged inpatient stay of > 25 days and an intensive care stay of > 13 days. Among other, the influence of the cause of the accident, injury patterns according to body regions, the occurrence of complications, and the influence of numerous clinical parameters were examined. RESULTS: A total of 23,026 patients with a mean age of 76.6 years and a mean ISS of 24 points were included. Mean ICU length of stay was 11 ± 12.9 days (regular length of stay: 3.9 ± 3.1d vs. prolonged length of stay: 12.8 ± 5.7d) and mean inpatient stay was 22.5 ± 18.9 days (regular length of stay: 20.7 ± 15d vs. 35.7 ± 22.3d). A total of n = 6,447 patients met the criteria for a prolonged length of stay. Among these, patients had one more diagnosis on average (4.6 vs. 5.8 diagnoses) and had a higher ISS (21.8 ± 6 pts. vs. 26.9 ± 9.5 pts.) Independent risk factors for prolonged length of stay were intubation duration greater than 6 days (30-fold increased risk), occurrence of sepsis (4x), attempted suicide (3x), presence of extremity injury (2.3x), occurrence of a thromboembolic event (2.7x), and administration of red blood cell concentrates in the resuscitation room (1.9x). CONCLUSIONS: The present analysis identified numerous independent risk factors for significantly prolonged hospitalization of the geriatric polytraumatized patient, which should be given increased attention during treatment. In particular, the need for a smooth transition to psychiatric follow-up treatment or patient-adapted rehabilitative care for geriatric patients with prolonged immobility after extremity injuries is emphasized by these results.

Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort.

Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997-2000 with a risk of 5.6% and lowest between 2013-2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.

Assessment of Thrombotic Complications among Coronavirus Disease 2019 Positive Hospitalized Patients at One of Government Tertiary Care Centres of Gujarat: A Retrospective Observational Study.

OBJECTIVES: The objectives of the study were to (1) study risk factors of thrombotic complications in coronavirus disease 2019 (COVID-19) pneumonitis, and (2) study progression of thrombotic complications after COVID-19 pneumonitis and its outcome. MATERIALS AND METHODS: A total of 50 COVID-19-positive admitted patients were studied using a purposive random sampling method. A questionnaire was used to collect data from patients' case records. RESULTS: Diabetes (42%) and hypertension (40%) were common comorbidities. The most common presentation of patients was thromboembolism, followed by cerebrovascular accident (CVA) and myocardial infarction (MI). Around 32% of patients died during the course of treatment. Deaths were more commonly seen in the age-group of 56 years or above than in those below 56 years. Death rates were higher among the group of patients with diabetes, hypertension, and ischemic heart diseases than the group of patients without those diseases, respectively. Patients in whom intubation was needed had a higher death rate than those without the need for it. The mean C-reactive protein (CRP) value was higher in patients who died than in those who survived. The death rate was lower in patients who were thrombolysed than in those who were not, in both pulmonary embolism and MI cases. CONCLUSION: The most common age-group admitted to the hospital was 46-55 years. The two most common underlying risk factors were diabetes and hypertension. Three common presentations of patients were thromboembolism, followed by CVA and MI. Around 32% of patients died during the course of treatment. Deaths were more commonly seen in the age-group of 56 years or above than in those below 56 years. Death rates were higher among the group of patients with diabetes, hypertension, and ischemic heart diseases than the group of patients without those diseases, respectively. Patients in whom intubation was needed had a higher death rate than those without the need for it. The mean CRP value was higher in patients who died than in those who survived.

Machine learning-based model to predict composite thromboembolic events among Chinese elderly patients with atrial fibrillation.

OBJECTIVE: Accurate prediction of survival prognosis is helpful to guide clinical decision-making. The aim of this study was to develop a model using machine learning techniques to predict the occurrence of composite thromboembolic events (CTEs) in elderly patients with atrial fibrillation(AF). These events encompass newly diagnosed cerebral ischemia events, cardiovascular events, pulmonary embolism, and lower extremity arterial embolism. METHODS: This retrospective study included 6,079 elderly hospitalized patients (≥ 75 years old) with AF admitted to the People's Liberation Army General Hospital in China from January 2010 to June 2022. Random forest imputation was used for handling missing data. In the descriptive statistics section, patients were divided into two groups based on the occurrence of CTEs, and differences between the two groups were analyzed using chi-square tests for categorical variables and rank-sum tests for continuous variables. In the machine learning section, the patients were randomly divided into a training dataset (n = 4,225) and a validation dataset (n = 1,824) in a 7:3 ratio. Four machine learning models (logistic regression, decision tree, random forest, XGBoost) were trained on the training dataset and validated on the validation dataset. RESULTS: The incidence of composite thromboembolic events was 19.53%. The Least Absolute Shrinkage and Selection Operator (LASSO) method, using 5-fold cross-validation, was applied to the training dataset and identified a total of 18 features that exhibited a significant association with the occurrence of CTEs. The random forest model outperformed other models in terms of area under the curve (ACC: 0.9144, SEN: 0.7725, SPE: 0.9489, AUC: 0.927, 95% CI: 0.9105-0.9443). The random forest model also showed good clinical validity based on the clinical decision curve. The Shapley Additive exPlanations (SHAP) showed that the top five features associated with the model were history of ischemic stroke, high triglyceride (TG), high total cholesterol (TC), high plasma D-dimer, age. CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of CTEs. The random forest model has good performance. History of ischemic stroke, age, high TG, high TC and high plasma D-Dimer may be correlated with CTEs.

[Translation into French and republication of: "Cancer-related arterial thromboembolic events"]. / Traduction et republication de : « Événements thromboemboliques artériels liés au cancer ¼.

Cancer is associated with a hypercoagulable state and is a well-known independent risk factor for venous thromboembolism, whereas the association between cancer and arterial thromboembolism is less well established. Arterial thromboembolism, primarily defined as myocardial infarction or stroke is significantly more frequent in patients with cancer, independently of vascular risk factors and associated with a three-fold increase in the risk of mortality. Patients with brain cancer, lung cancer, colorectal cancer and pancreatic cancer have the highest relative risk of developing arterial thromboembolism. Antithrombotic treatments should be used with caution due to the increased risk of haemorrhage, as specified in current practice guidelines.

[Chinese expert consensus on home management of oral anticoagulants(2024 edition)].

Oral anticoagulants are widely used in the home care of patients who require prevention and treatment of thromboembolic diseases. The irrational use of anticoagulants may cause thrombosis and hemorrhage. Currently, there are no national or international guidelines or consensus providing recommendations for home management of oral anticoagulants. Therefore, the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association organized domestic experts in the fields of clinical pharmacy, cardiovascular surgery, cardiovascular medicine, vascular surgery, respiratory medicine and laboratory science to sort out the relevant issues and compile the expert consensus on the home management of oral anticoagulants. The main contents of this consensus include pharmacological monitoring of oral anticoagulants, the process and precautions of carrying out home management of oral anticoagulants, and treatment of some special conditions during home management, with the aim of enhancing the safety and effectiveness of oral anticoagulants' usage and reducing the adverse events.

Association Between Aortic Wall Thrombus and Thromboembolic Events After Transfemoral Transcatheter Aortic Valve Replacement.

BACKGROUND: Thromboembolic events, particularly strokes, remain a major complication of transcatheter aortic valve replacement (TAVR). Embolic protection devices have failed to show significant clinical benefit in large randomized clinical trials. Aortic wall thrombus (AWT) is often observed on multidetector computed tomography during TAVR work-up, but its prognostic significance is uncertain. OBJECTIVES: This study sought to evaluate the association between the presence of AWT and the incidence of thromboembolic outcomes in patients undergoing transfemoral (TF) TAVR for severe aortic stenosis. METHODS: This was a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between January 2011 and April 2022. A dedicated scale (range: 0-10) was qualitatively used to assess AWT. The primary outcome was a composite of procedural thromboembolic events defined as ischemic stroke, blue toe syndrome, bowel ischemia, or other solid organ infarction. The secondary endpoints were ischemic strokes and procedural death. RESULTS: Of the 641 patients included, severe AWT (score ≥8) was identified in 73 (11.4%). The presence of severe AWT was strongly associated with an increase in the primary outcome (OR: 8.48; 95% CI: 3.36-21.40; P < 0.001). This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics. The presence of severe AWT was also found to be associated with an increased incidence of stroke and procedural death (OR: 5.66; 95% CI: 2.00-15.30; P = 0.002 and OR: 4.66; 95% CI: 1.80-11.30; P = 0.002, respectively). CONCLUSIONS: The presence of severe AWT on preprocedural multidetector computed tomography is strongly associated with thromboembolic complications including stroke and mortality after TF TAVR.

Morphology and location of thrombus and sludge in patients with non-valvular atrial fibrillation.

BACKGROUND: Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. METHODS: We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. RESULTS: Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. CONCLUSION: This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. CLINICAL TRIAL NUMBER: ChiCTR-OCH-13,003,729.

Multiple Thromboembolic Events in Young Patient with Homozygous T-786C Mutation in the Endothelial Nitric Oxide Synthase Gene (ENOS).

Thromboembolic events are a common cause of morbidity and mortality with significant socioeconomic impact especially when young patients are affected. They are a rare medical event in young people and their clinical presentation can be mild or asymptomatic. The manifestation of symptoms and thrombotic events depends on both: the genetic mutations and the external risk factors that will induce the process. We present a case of a 34-year old young female, with three consecutive cerebrovascular insults in a period of ten years, and an acute myocardial infarction. There is a combination of gene mutations and polymorphism, with a predisposition to thromboembolic events. We emphasized the role of e-NOS (Endothelial nitric oxide synthase 786 T>C mutation) and the connection with smoking. The dual effect of the prolonged smoking and dysfunctional nitric oxide synthase in our young patient led to several thrombotic events. We discussed the various diagnostic tests and possible therapeutic and prophylactic strategies.

Antithrombotic Therapy for Heart Failure in Sinus Rhythm - A Concise Review.

Heart failure (HF) is a common disorder associated with significant morbidity and mortality. It can increase the risk of thromboembolic events, which subsequently lead to increased risk of stroke, ischemic heart disease, thromboembolism, and death. Antithrombotic therapy has been investigated as a potential management strategy for HF patients in sinus rhythm, but its efficacy remains uncertain. Current guidelines do not recommend the routine use of antithrombotics in patients with HF in sinus rhythm without any other indication for their use. Several randomized controlled trials have investigated the efficacy of antithrombotics in HF patients in sinus rhythm. This article provides a concise review of the existing literature to assess the evidence supporting the use of antithrombotics in HF patients in sinus rhythm. The use of warfarin or other anticoagulants has demonstrated a lower risk of stroke but an increased risk of bleeding. The studies demonstrate that anticoagulant therapy in HF patients in sinus rhythm does not provide significant benefits in terms of overall ischemic events or death.

Case Report: Non-ischemic Papillary Muscle Rupture due to MRSA Myocarditis with Concurrent Thromboembolic Myocardial Infarction Secondary to Infective Endocarditis.

Non-ischemic papillary muscle rupture (PMR) is rare. PMR caused by myocarditis in the presence of concurrent infective endocarditis (IE) and myocardial infarction (MI) has not been described. We report a 46-year-old male with recurrent MRSA bacteremia who presented in septic shock and suffered cardiac arrest. Echocardiography revealed acute mitral valve regurgitation resulting from posteromedial PMR. An intra-aortic balloon pump was implanted. Angiography revealed thrombotic occlusion of a small distal left circumflex artery. Emergent mitral valve replacement surgery was performed. MRSA myocarditis and IE were diagnosed by tissue cultures. Coexistence of myocarditis, IE, and MI poses a challenge in determining etiology.

Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

BACKGROUND: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. METHODS: A systematic review and meta-analysis was performed. RESULTS: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%). CONCLUSION: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

Direct Aspiration Thrombectomy in the Management of Procedural Thromboembolic Complications Related to Endovascular Brain Aneurysm Treatment.

Despite growing evidence over the last few years of the efficacy and safety of direct thrombus aspiration using a large bore distal access catheter as a type of mechanical thrombectomy procedure in acute stroke large-vessel occlusion patients, the experience and evidence of this technique for managing thromboembolic complications in endovascular aneurysm treatment is still limited and little research is available regarding this topic. We present a case of a thromboembolic occlusion of the left middle cerebral artery during the preprocedural angiograms of a large and fusiform left internal carotid artery aneurysm. This complication was successfully managed by navigating an already-placed distal access catheter intended for support during the opening of the flow-diverting stent; therefore, the thrombus was manually aspirated for two minutes, and Thrombolysis in Cerebral Infarction (TICI) scale 3 flow was restored. This case should encourage the use of a distal access catheter, already placed for aneurysm treatment, to perform zero-delay direct thrombus aspiration as a rescue approach for thromboembolic complications during endovascular treatments.

Direct-Acting Oral Anticoagulants and Antiseizure Medications for Atrial Fibrillation and Epilepsy and Risk of Thromboembolic Events.

Importance: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk. Objective: To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs. Design, Setting, and Participants: This active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy. Exposure: Evaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy. Main Outcomes and Measures: Thromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs. Results: This study included 14 078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14 158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89). Conclusions and Relevance: In this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.

Feline aortic thromboembolism with and without congestive heart failure did not exhibit hypercoagulability using a novel viscoelastic coagulation monitor.

OBJECTIVE: To demonstrate hypercoagulability with a benchtop viscoelastic monitor in cats with congestive heart failure (CHF) and/or aortic thromboembolism (ATE) compared to controls. METHODS: 97 cats were enrolled throughout this prospective observational cohort study from September 2022 through October 2023. Cats were grouped by diagnosis of CHF, ATE, ATE plus CHF, or controls. Enrollment required diagnosis of heart disease and no previous antithrombotic therapy. The results of viscoelastic testing with the benchtop viscoelastic coagulation monitor (VCM Vet [VCM]; Entegrion) were compared between groups using factorial analysis of variance. RESULTS: Cats with heart disease had significantly higher clot times when compared to controls (control: mean, 285.3 [SD, 172.6]; CHF: mean, 391.7 [SD, 106.8]; ATE: mean, 415.9 [SD, 109.2]; and ATE plus CHF: mean, 368.6 [SD, 232.6]). Heart disease cats were noted to have significantly lower 45-minute lysis index values (control: median, 100 [range, 93 to 100]; CHF: median, 99 [range, 89 to 100]; ATE: median, 98 [range, 88 to 100]; and ATE plus CHF: range, 98 [91 to 100]). Age was a covariate to this variable, and when applied to analysis, statistical significance was lost. No significant difference in any other variables were noted. CLINICAL RELEVANCE: The hypercoagulability of ATE and CHF cats was not detected by the VCM. Further research with other coagulation monitors is required in this population.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

BACKGROUND: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs. METHODS: This prospective, observational study enrolled patients with NSCLC concomitantly using a DOAC and SMI. The primary outcome was the proportion of patients with DOAC plasma trough (Ctrough) and peak (Cpeak) concentrations outside expected ranges. Secondary outcomes included DOAC treatment modifications, incidence of bleeding and thromboembolic events and feasibility evaluation of pharmacokinetically guided DOAC dosing. RESULTS: Thirty-three patients were analysed. Thirty-nine percent (13/33) had DOAC Ctrough and/or Cpeak were outside the expected ranges in 39% (13/33). In 71% (5/7) of patients with DOAC concentrations quantified before and during concurrent SMI use, DOAC Ctrough and/or Cpeak increased or decreased >50% upon SMI initiation. In all patients in whom treatment modifications were deemed necessary, DOAC concentrations were adjusted to within the expected ranges. CONCLUSION: Proactive monitoring showed that a substantial proportion of patients had DOAC concentrations outside the expected ranges. DOAC concentrations were successfully normalised after treatment modifications. These results highlight the importance of proactive monitoring of DOAC-SMI DDIs to improve treatment in patients with NSCLC.