Unmet needs and barriers in venous thromboembolism education and awareness among people living with cancer: a global survey.

BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored. RESULTS: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSION: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management.

Drug-drug interactions between direct oral anticoagulants and anticonvulsants and clinical outcomes: A systematic review.

Background: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. However, DOACs have important potential drug-drug interactions (DDIs) with several classes of drugs. In particular, antiepileptic (AE) drugs may induce cytochrome P450 3A4 or P-glycoprotein. Co-administration of DOACs and AE drugs may result in lower DOAC drug levels and reduced DOAC efficacy. However, the clinical significance of such DDIs is uncertain. Objectives: The aim of this systematic review was to generate an updated review of these DDIs and their clinical relevance, given the rapidly evolving knowledge relating to DOAC and AE DDIs. Methods: We searched the MEDLINE and Embase databases for studies reporting clinical adverse outcomes (thrombotic events, bleeding events, and all-cause mortality) in patients concomitantly taking DOACs and AE drugs. Results: We retrieved 874 studies of which 15 were deemed eligible for this review, including 4 congress abstracts, 3 case reports, 2 letters to the editor, 5 retrospective cohorts, and 1 prospective cohort study. No randomized clinical trials were found. Most of the included studies reported thrombotic events, 3 studies reported major bleeding, and one study reported all-cause mortality associated with DOAC and AE drug administration. Substantial differences in the study designs did not allow for a meta-analysis to be performed. Conclusion: The current literature assessing these adverse clinical outcomes from DOAC and AE drug co-administration is limited. Although the available data point to a possible increased risk of thrombotic events, they are insufficient to draw definitive conclusions. Well-designed clinical studies are of utmost importance.

Prognostic role of different findings at echocardiography in acute pulmonary embolism: a critical review and meta-analysis.

Background: Right ventricle dysfunction (RVD) at echocardiography predicts mortality in patients with acute pulmonary embolism (PE), but heterogeneous definitions of RVD have been used. We performed a meta-analysis to assess the role of different definitions of RVD and of individual parameters of RVD as predictors of death. Methods: A systematic search for studies including patients with confirmed PE reporting on right ventricle (RV) assessment at echocardiography and death in the acute phase was performed. The primary study outcome was death in-hospital or at 30 days. Results: RVD at echocardiography, regardless of its definition, was associated with increased risk of death (risk ratio 1.49, 95% CI 1.24-1.79, I2=64%) and PE-related death (risk ratio 3.77, 95% CI 1.61-8.80, I2=0%) in all-comers with PE, and with death in haemodynamically stable patients (risk ratio 1.52, 95% CI 1.15-2.00, I2=73%). The association with death was confirmed for RVD defined as the presence of at least one criterion or at least two criteria for RV overload. In all-comers with PE, increased RV/left ventricle (LV) ratio (risk ratio 1.61, 95% CI 1.90-2.39) and abnormal tricuspid annular plane systolic excursion (TAPSE) (risk ratio 2.29 CI 1.45-3.59) but not increased RV diameter were associated with death; in haemodynamically stable patients, neither RV/LV ratio (risk ratio 1.11, 95% CI 0.91-1.35) nor TAPSE (risk ratio 2.29, 95% CI 0.97-5.44) were significantly associated with death. Conclusion: Echocardiography showing RVD is a useful tool for risk stratification in all-comers with acute PE and in haemodynamically stable patients. The prognostic value of individual parameters of RVD in haemodynamically stable patients remains controversial.

Anticoagulant Management and Outcomes in Nontraumatic Intracranial Hemorrhage Complicated by Venous Thromboembolism: A Retrospective Chart Review.

BACKGROUND: There are limited data on anticoagulant management of acute venous thromboembolism (VTE) after spontaneous intracranial hemorrhage (ICH). METHODS: We reviewed retrospectively all cases diagnosed with VTE during hospitalization for spontaneous ICH at our center during 15 years. Anticoagulation management outcomes were (1) timing after ICH of anticoagulant initiation for VTE treatment, (2) use of immediate therapeutic dosing or stepwise dose escalation, and (3) the proportion achieving therapeutic dose. Primary clinical effectiveness outcome was recurrent VTE. Primary safety outcome was expanding ICH. RESULTS: We analyzed 103 cases with VTE after 11 days (median; interquartile range [IQR]: 7-22) from the diagnosis of ICH. Forty patients (39%) achieved therapeutic anticoagulation 21.5 days (median; IQR: 14-34 days) from the ICH. Of those, 14 (35%; 14% of total) received immediately therapeutic dose and 26 (65%; 25% of total) had stepwise escalation. Anticoagulation was more aggressive in patients with VTE >14 days after admission versus those with earlier VTE diagnosis. Twenty-two patients (21%) experienced recurrent/progressive VTE-less frequently among patients with treatment escalation within 7 days or with no escalation than with escalation >7 days from the VTE. There were 19 deaths 6 days (median; IQR: 3.5-15) after the index VTE, with significantly higher in-hospital mortality rate among patients without escalation in anticoagulation. CONCLUSION: Prompt therapeutic anticoagulation for acute VTE seems safe when occurring more than 14 days after spontaneous ICH. For VTE occurring earlier, it might also be safe with therapeutic anticoagulation, but stepwise dose escalation to therapeutic within a 7-day period might be preferable.

Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis.

BACKGROUND: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. OBJECTIVES: The objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT. METHODS: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate. RESULTS: In total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35). CONCLUSION: Patients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT.

Age- versus clinical pretest probability-adjusted D-dimer to rule out lower-extremity deep vein thrombosis in ambulatory patients with active cancer.

BACKGROUND: In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain. AIM: To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule. PATIENTS AND METHODS: Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism. RESULTS: Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate. CONCLUSIONS: In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting.

Antithrombotic treatment for retinal vein occlusion: a systematic review and meta-analysis.

BACKGROUND: Retinal vein occlusion (RVO) represents a common thrombotic disorder. OBJECTIVES: In this meta-analysis, we evaluated the efficacy and safety of anticoagulant and antiplatelet therapy in RVO. METHODS: MEDLINE and EMBASE were searched up to December 2021 for observational studies and randomized controlled trials including patients with RVO. Efficacy outcomes were best-corrected visual acuity improvement, recurrent RVO, fluorescein angiography improvement, cardiovascular events, and safety outcomes were major bleeding and intraocular bleeding. RESULTS: A total of 1422 patients (15 studies) were included. Antiplatelet therapy was administered to 477 patients (13 studies), anticoagulant therapy to 312 patients (12 studies), and 609 (7 studies) patients received no antithrombotic treatment. The treatment duration ranged between 0.5 and 3 months. The median follow-up duration was 12 months. Best-corrected visual acuity improvement was reported in 58% of the patients (95% confidence interval [CI], 45%-69%) overall, 64% (95% CI, 58%-71%) in those on anticoagulant therapy, and 33% (95% CI, 21%-47%) in those on antiplatelet therapy. The rates of recurrent RVO was 11% (95% CI, 7%-17%), 7% (95% CI, 2%-19%), and 15% (95% CI, 8%-28%), respectively. The rate of recurrent RVO in untreated patients was 9% (95% CI, 6%-14%). The rate of major bleeding was 5% (95% CI, 3%-9%) overall, 4% (95% CI, 2%-9%) in those on anticoagulant therapy, and 7% (95% CI, 2%-23%) in those on antiplatelet therapy. CONCLUSION: Anticoagulant therapy was associated with higher visual acuity improvement and fewer recurrent RVO events than antiplatelet therapy, at the cost of an acceptable proportion of bleeding complications.

Anamnestic frailty phenotype and adverse outcomes in patients treated with direct oral anticoagulants: Validation and comparative performance with frailty phenotype.

AIMS: The anamnestic frailty phenotype (AFP) is a quick, instrument-free tool derived from frailty phenotype (FP). We prospectively evaluated the discriminative capacity and prognostic value of AFP in ambulatory patients receiving DOACs for atrial fibrillation (AF) or venous thromboembolism (VTE), and compared AFP performance with that of FP. METHODS AND RESULTS: Sensitivity, specificity, positive and negative predictive value (PPV, NPV) with corresponding 95% confidence intervals (95%CI), were estimated for bleeding, thromboembolism, and all-cause mortality. Risk ratios (RRs) were calculated in frail versus non-frail patients. Of 236 patients (median age 78 years), 98 (42%) and 89 (38%) were classified as frail according to FP and AFP, respectively (Kappa= 0.76). Frailty, as assessed by AFP, was associated with higher risk of bleeding (RR 2.3; 95%CI, 1.2 to 4.6), and mortality (RR 4.4; 95%CI, 1.3 to 19.7). Similarly, to FP, AFP exhibited modest sensitivity and specificity, but high NPV that was 91% (95%CI, 85 to 95) for bleeding, 98% (95%CI, 94 to 100) for thromboembolism, and 98% (95%CI, 94 to 100) for mortality. CONCLUSION: Among patients receiving DOACs for AF or VTE, AFP was associated with an increased risk of adverse outcomes. AFP exhibited modest sensitivity and specificity, but excellent NPV. If confirmed, these findings suggest that AFP may represent a rapid, easy-to-use and unexpensive tool that may potentially help identify patients at lower risk for adverse outcomes and tailor anticoagulation management.

Arterial Thrombotic Events in Hospitalized COVID-19 Patients: A Short Review and Meta-Analysis.

It is well established that the risk of venous thromboembolism is high in coronavirus disease 19 (COVID-19). The frequency of arterial thromboembolic events (ATEs) in hospitalized patients with COVID-19 is unclear, as is the magnitude of these events in comparison with other infections. We searched MEDLINE from February 2020 to February 2022 for prospective or retrospective cohort studies and randomized clinical trials that reported the number of acute myocardial infarction (AMI), acute ischemic stroke (AIS), acute limb ischemia (ALI), or other ATE as defined by the original authors in hospitalized patients with COVID-19. The pooled frequencies were calculated through meta-analysis using random effects model with logit transformation and presented with relative 95% prediction intervals (95% PI). We retrieved a total of 4,547 studies, 36 of which (28 retrospective cohorts, five prospective cohorts and three randomized trials) were finally included in our analysis. The resulting cohort counted 100,949 patients, 2,641 (2.6%) of whom experienced ATE. The pooled ATE frequency was 2.0% (95% PI, 0.4-9.6%). The pooled ATE frequency for AMI, AIS, ALI, and other ATE was 0.8% (95% PI, 0.1-8.1%), 0.9% (95% PI, 0.3-2.9%), 0.2% (95% PI, 0.0-4.2%), and 0.5% (95% PI, 0.1-3.0%), respectively. In comparison with the ATE incidence reported in three studies on non-COVID viral pneumonia, we did not detect a significant difference from the results in our analysis. In conclusion, we found a non-negligible proportion of ATE in patients hospitalized for COVID-19. Our results are similar to those found in hospitalized patients with influenza or with non-COVID viral pneumonia.

Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants.

BACKGROUND: Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC-treated patients at higher risk of adverse clinical outcomes. METHODS: Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre-frail, or non-frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non-major bleeding, arterial and venous thromboembolism, and all-cause mortality. RESULTS: 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety-eight (41%) patients were frail, 115 (49%) pre-frail, and 23 (10%) non-frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non-frail or pre-frail patients. Over a median follow-up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre-frail, respectively, while no study outcome occurred among non-frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre-frail and non-frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6). CONCLUSION: In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all-cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis.

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis.

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.

Unanswered questions in cancer-associated thrombosis.

Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. Treatment of cancer-associated VTE comes with a heightened risk of anticoagulant-related bleeding that differs by choice of anticoagulant as well as by patient- and disease-specific risk factors. Available data from randomized controlled trials and observational studies in cancer-associated VTE suggest that direct oral anticoagulants are effective, continuing anticoagulation beyond six months is indicated in those with active cancer and that patients who develop 'breakthrough' thrombotic events can be effectively treated. We review the evidence that addresses these key clinical questions and offer pragmatic approaches in individualizing care. While significant investigative efforts over the past decade have made impactful advances, future research is needed to better define the factors that contribute to anticoagulant-related bleeding and VTE recurrence, in order to aid clinical decision-making that improves the care of patients with cancer-associated VTE.

Carbamazepine, phenytoin, and oral anticoagulants: Drug-drug interaction and clinical events in a retrospective cohort.

BACKGROUND: Carbamazepine and phenytoin are potent inducers of enzymes that metabolize oral anticoagulants. OBJECTIVES: To determine the clinical impact of drug-drug interactions between these anticonvulsants and oral anticoagulants, and whether they affect the treatment with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). MATERIAL AND METHODS: Data on patients cotreated with carbamazepine or phenytoin and an oral anticoagulant were retrospectively retrieved from medical records from 2011 to 2020. Outcomes were time in therapeutic range (TTR), DOAC levels, thromboembolic events, major bleeding, and all-cause mortality. RESULTS: Among 85 patients (37% female, median age 68 years) treated with carbamazepine (n = 43 [51%]) or phenytoin (n = 42 [49%]), 53 (62%) were initially treated with VKAs and 32 (38%) with DOACs. TTR in VKA patients was 63%, which improved in year 2. Four of seven trough and five of 12 peak DOAC plasma levels were lower than expected. The incidence rate (95% confidence interval) per 100 person-years for thromboembolism was 3.6 (3.1-4.2) for VKA patients and 4.4 (3.5-5.6) for DOAC patients; for major bleeding 1.8 (1.5-2.1) and 1.5 (1.2-1.9), and for all-cause mortality 3.6 (3.1-4.2) and 1.5 (1.2-1.9), respectively. Incidence rates between VKAs and DOACs and between carbamazepine and phenytoin were similar. CONCLUSION: There was a high incidence of thromboembolism in patients cotreated with anticoagulants and carbamazepine or phenytoin. The incidence rates of thrombotic and bleeding events were similar between VKA and DOAC patients. DOAC levels were lower than expected in 47% of cases tested, without correlation with clinical outcomes.

Direct oral anticoagulant plasma levels in hospitalized COVID-19 patients treated with dexamethasone.

Direct oral anticoagulants (DOACs) are not recommended in COVID-19 patients receiving dexamethasone because of potential drug-drug and drug-disease interactions affecting anticoagulant concentration and activity. To evaluate short- and long-term pharmacokinetic interactions, serial through and peak DOAC plasma levels were prospectively measured during and after dexamethasone therapy, as well as during the acute phase and after recovery from COVID-19 in hospitalized, non-critically ill patients undergoing treatment with DOACs. Thirty-three (18 males, mean age 79 years) consecutive patients received DOACs (17 apixaban, 12 rivaroxaban, 4 edoxaban) for atrial fibrillation (n = 22), venous thromboembolism (n = 10), and acute myocardial infarction (n = 1). Twenty-six patients also received dexamethasone at a dose of 6 mg once daily for a median of 14 days. Trough DOAC levels on dexamethasone were within and below expected reference ranges respectively in 87.5 and 8.3% of patients, with no statistically significant differences at 48-72 h and 14-21 days after dexamethasone discontinuation. Peak DOAC levels on dexamethasone were within expected reference ranges in 58.3% of patients, and below ranges in 33.3%, of whom over two thirds had low values also off dexamethasone. No significant differences in DOAC levels were found during hospitalization and after resolution of COVID-19. Overall, 28 patients were discharged alive, and none experienced thrombotic or bleeding events. In this study, dexamethasone administration or acute COVID-19 seemed not to affect DOAC levels in hospitalized, non-critically ill COVID-19 patients.

Extended venous thromboprophylaxis in patients hospitalized for acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Patients hospitalized for acute ischemic stroke have an increased risk of venous thromboembolism (VTE) that may persist beyond the currently recommended period of 6 to 14 days of thromboprophylaxis. This systematic review evaluated the efficacy and safety of extended venous thromboprophylaxis in patients hospitalized for acute ischemic stroke. MATERIALS AND METHODS: MEDLINE, EMBASE and Clinicaltrials.gov were searched up to December 2020 for randomized controlled trials comparing extended versus standard venous thromboprophylaxis in patients hospitalized for acute ischemic stroke. The efficacy outcome was a composite of asymptomatic or symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and VTE-related death. The safety outcome was major bleeding. Summary risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Four randomized controlled trials enrolling 33718 patients were included. Of 4330 (12.8%) patients hospitalized for acute ischemic stroke, 2152 (49.7%) received extended thromboprophylaxis for four to five weeks with betrixaban (n = 405, 18.8%), enoxaparin (n = 198, 9.2%), or rivaroxaban (n = 1549, 72.0%), and 2178 (50.3%) received standard venous thromboprophylaxis with enoxaparin. VTE risk was lower in acute ischemic stroke patients receiving extended thromboprophylaxis (RR 0.67; 95% CI, 0.43 to 1.04; 13 fewer per 1000), whereas the increase in major bleeding seemed trivial when compared with standard prophylaxis (RR 1.10; 95% CI, 0.31 to 3.95; 1 more per 1000). CONCLUSION: In patients hospitalized for acute ischemic stroke, the net clinical benefit may favor extended venous thromboprophylaxis for four to five weeks over standard thromboprophylaxis.

Aliased Flow Signal Planimetry by Cardiovascular Magnetic Resonance Imaging for Grading Aortic Stenosis Severity: A Prospective Pilot Study.

Objectives: Transthoracic echocardiography (TTE) is the standard technique for assessing aortic stenosis (AS), with effective orifice area (EOA) recommended for grading severity. EOA is operator-dependent, influenced by a number of pitfalls and requires multiple measurements introducing independent and random sources of error. We tested the diagnostic accuracy and precision of aliased orifice area planimetry (AOAcmr), a new, simple, non-invasive technique for grading of AS severity by low-VENC phase-contrast cardiovascular magnetic resonance (CMR) imaging. Methods: Twenty-two consecutive patients with mild, moderate, or severe AS and six age- and sex-matched healthy controls had TTE and CMR examinations on the same day. We performed analysis of agreement and correlation among (i) AOAcmr; (ii) geometric orifice area (GOAcmr) by direct CMR planimetry; (iii) EOAecho by TTE-continuity equation; and (iv) the "gold standard" multimodality EOA (EOAhybrid) obtained by substituting CMR LVOT area into Doppler continuity equation. Results: There was excellent pairwise positive linear correlation among AOAcmr, EOAhybrid, GOAcmr, and EOAecho (p < 0.001); AOAcmr had the highest correlation with EOAhybrid (R 2 = 0.985, p < 0.001). There was good agreement between methods, with the lowest bias (0.019) for the comparison between AOAcmr and EOAhybrid. AOAcmr yielded excellent intra- and inter-rater reliability (intraclass correlation coefficient: 0.997 and 0.998, respectively). Conclusions: Aliased orifice area planimetry by 2D phase contrast imaging is a simple, reproducible, accurate "one-stop shop" CMR method for grading AS, potentially useful when echocardiographic severity assessment is inconclusive or discordant. Larger studies are warranted to confirm and validate these promising preliminary results.

Recurrent bleeding and thrombotic events after resumption of oral anticoagulants following gastrointestinal bleeding: Communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

BACKGROUND: Gastrointestinal bleeding frequently complicates anticoagulant therapy causing treatment discontinuation. Data to guide the decision regarding whether and when to resume anticoagulation based on the risks of thromboembolism and recurrent bleeding are scarce. OBJECTIVES: We aimed to retrospectively evaluate the incidence of these events after anticoagulant-related gastrointestinal bleeding and assess their relationship with timing of anticoagulation resumption. METHODS: Patients hospitalized because of gastrointestinal bleeding during oral anticoagulation for any indication were eligible. All patients were followed up to 2 years after the index bleeding for recurrent major or clinically relevant non-major bleeding, venous or arterial thromboembolism, and mortality. RESULTS: We included 948 patients hospitalized for gastrointestinal bleeding occurring during treatment with vitamin K antagonists (n = 531) or direct oral anticoagulants (n = 417). In time-dependent analysis, anticoagulant treatment was associated with a higher risk of recurrent clinically relevant bleeding (hazard ratio [HR] 1.55; 95% confidence interval [CI] 1.08-2.22), but lower risk of thromboembolism (HR 0.34; 95% CI 0.21-0.55), and death (HR 0.50; 95% CI 0.36-0.68). Previous bleeding, index major bleeding, and lower glomerular filtration rate were associated with a higher risk of recurrent bleeding. The incidence of recurrent bleeding increased after anticoagulation restart independently of timing of resumption. CONCLUSIONS: Anticoagulant treatment after gastrointestinal bleeding is associated with a lower risk of thromboembolism and death, but higher risk of recurrent bleeding. The latter seemed to be influenced by patient characteristics and less impacted by time of anticoagulation resumption.

Risk Assessment Models for Thrombosis and Anticoagulant-Related Bleeding in Ambulatory Cancer Patients.

Cancer patients have a high risk of developing venous thromboembolism and arterial thrombosis, along with an increased risk of anticoagulant-related bleeding with primary and secondary prophylaxis of cancer-associated thrombosis. Decisions on initiation, dosing, and duration of anticoagulant therapy for prevention and treatment of cancer-associated thrombosis are challenging, as clinicians have to balance patients' individual risk of (recurrent) thrombosis against the risk of bleeding complications. For this purpose, several dedicated risk assessment models for venous thromboembolism in cancer patients have been suggested. However, most of these scores perform poorly and have received limited to no validation. For bleeding and arterial thrombosis, no risk scores have been developed specifically for cancer patients, and treatment decisions remain based on clinical gestalt and rough and unstructured estimation of the risks. The aims of this review are to summarize the characteristics and performance of risk assessment scores for (recurrent) venous thromboembolism and discuss available data on risk assessment for bleeding and arterial thrombosis in the cancer population. This summary can help clinicians in daily practice to make a balanced decision when considering the use of risk assessment models for cancer-associated venous thromboembolism. Future research attempts should aim at improving risk assessment for arterial thrombosis and anticoagulant-related bleeding in cancer patients.

Management of upper extremity deep vein thrombosis: an updated review of the literature.

Upper extremity deep vein thrombosis (UEDVT) represents about 5-10% of all cases of deep vein thrombosis (DVT) with a steadily increasing incidence mostly due to the high prevalence of cancer and frequent use of intravascular devices such as central venous catheters and pacemaker. In primary UEDVT, the venous outflow obstruction and subsequent thrombosis are related to congenital or acquired anatomical abnormalities, whereas secondary UEDVT is often associated with malignancy or indwelling lines. A considerable proportion of patients with UEDVT develops serious complications such as recurrent thrombosis, post-thrombotic syndrome, and pulmonary embolism, therefore timely diagnosis and adequate treatment are of crucial importance. Despite sharing many similarities with lower extremity DVT, UEDVT has distinctive features requiring specific diagnostic and therapeutic approaches. The present review discusses the latest evidence on the epidemiology, diagnosis, and treatment of UEDVT, and provides management indications which may help guide clinical decision making.