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Background: The role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain. Objectives: We aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients. Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883). Results: We included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies. Conclusion: There is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE.
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BACKGROUND: Pulmonary vein thrombosis (PVT) is a rare thromboembolic disease with potential high-risk complications related to arterial embolization, but little is known regarding risk factors and outcomes. OBJECTIVE: To describe the etiology, management, and clinical course of PVT. METHODS: Institutional health records were queried (1/1/2001-12/30/2023) to identify patients ≥18 years of age diagnosed with PVT. Thrombosis, bleeding, respiratory failure, and all-cause mortality were analyzed. Suspected tumor thrombus cases were excluded. RESULTS: 72 patients with PVT were identified (median age 62 years, 50 % female), and PVT was overall rare at 3.1 diagnosed cases per year at our institution. PVT primarily affected a single vein (89 %), most commonly the left upper PV (40 %). Of these, 37 % occurred while on therapeutic anticoagulation. The most common risk factors included cancer (55 %) and related surgical lobectomy (21 %). Extrinsic vein compression (17 %) and recent surgery (19 %) were also common; 19 % were deemed idiopathic. Most patients (76 %) were treated with anticoagulation and frequently indefinite duration (80 %). During a median follow-up of 11.7 months (IQR 39.5 months), serial imaging (available for 68 %) revealed PVT resolution in 64 %. Four-year Kaplan-Meier probability of outcome included: left atrial thrombus (21 %), need for mechanical ventilation (14 %), pneumonia (9 %), and ischemic stroke (9 %). The mortality rate was 46 % with median survival 14 months after PVT diagnosis. CONCLUSION: PVT is often associated with active malignancy, lobectomy, recent surgery, and extrinsic vein compression; 1 in 5 cases were idiopathic. Notable complications include left atrial thrombus with arterial embolism including stroke. With anticoagulation, most thrombi resolve over time. Mortality rates are high, reflecting the high the prevalence of cancer.
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Pulmonary Veins , Venous Thrombosis , Humans , Female , Male , Middle Aged , Venous Thrombosis/etiology , Pulmonary Veins/pathology , Aged , Risk Factors , Treatment OutcomeSubject(s)
Liver Cirrhosis , Portal Vein , Venous Thrombosis , Humans , Portal Vein/diagnostic imaging , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Venous Thrombosis/etiology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/diagnosis , Venous Thrombosis/therapy , Anticoagulants/therapeutic use , Treatment Outcome , Risk FactorsABSTRACT
AIMS: Echocardiographic assessment of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) is limited to case reports and small clinical series. The study aimed to identify heart valve abnormalities and its relation to embolic complications and cancer types. METHODS AND RESULTS: Manual review of echocardiographic images and medical records of Mayo Clinic patients (31 March 2002-30 June 2022) was performed. Ca-NBTE in 111 patients (mean age 63.2 ± 9.7 years, 66.7% female) predominantly affected mitral valves (MV) (69), 56 aortic (AV), 8 tricuspid (TV), and rarely pulmonic (PV) (1). In 18 patients, 2 valves were involved, 3 and 4 valve involvement in only a single patient each. Embolic complications were prevalent (n = 102, 91.9%). Ca-NBTE affected MV more frequently on the upstream (atrial) (90% vs. 49.3%) and TV downstream (ventricular) side (75% vs. 37.5%). NBTE size (cm) varied significantly among valves, with TV hosting the largest masses (0.63-2.40 × 0.39-1.77), compared with MV [(0.11-1.81 × 0.11-1.62), (length P = 0.001; width P = 0.03)] and AV [(0.20-2.70 × 0.11-1.51), (length P = 0.001; width P = 0.056)]; MV masses were borderline longer in systemic compared with cerebral emboli (P = 0.057). Majority of MV (79.6%) and AV (69.6%) had thickened leaflets. NBTE lesions commonly affected closing margins (73.9% MV, 85.7% AV, and 62.5% of TV) but rarely commissures of MV (8.7%), yet fairly frequently of AV (41.1%). Five patients had severe regurgitation of MV and 5 AV. CONCLUSION: Ca-NBTE manifests mainly as thrombotic mobile masses attached to thickened MV and AV, with distinct variations in size based on valve type. Embolic destination but not cancer type is associated with NBTE mass size and location.
Subject(s)
Endocarditis, Non-Infective , Neoplasms , Humans , Female , Male , Middle Aged , Endocarditis, Non-Infective/diagnostic imaging , Endocarditis, Non-Infective/complications , Neoplasms/complications , Neoplasms/diagnostic imaging , Retrospective Studies , Echocardiography/methods , Aged , Thrombosis/diagnostic imagingABSTRACT
BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. RESULTS: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). CONCLUSION: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).
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Factor Xa Inhibitors , Hemorrhage , Neoplasms , Pyrazoles , Pyridones , Secondary Prevention , Venous Thromboembolism , Humans , Pyridones/administration & dosage , Pyridones/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Neoplasms/complications , Neoplasms/drug therapy , Venous Thromboembolism/prevention & control , Venous Thromboembolism/mortality , Venous Thromboembolism/drug therapy , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Female , Male , Middle Aged , Hemorrhage/chemically induced , Aged , Double-Blind Method , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/therapeutic use , Treatment Outcome , Time Factors , Anticoagulants/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Risk Factors , Drug Administration ScheduleABSTRACT
OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk for peripheral artery disease (PAD) and its complications. Arterial calcification and non-compressibility may limit test interpretation in this population. Developing tools capable of identifying PAD and predicting major adverse cardiac event (MACE) and limb event (MALE) outcomes among patients with DM would be clinically useful. Deep neural network analysis of resting Doppler arterial waveforms was used to detect PAD among patients with DM and to identify those at greatest risk for major adverse outcome events. METHODS: Consecutive patients with DM undergoing lower limb arterial testing (April 1, 2015-December 30, 2020) were randomly allocated to training, validation, and testing subsets (60%, 20%, and 20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict all-cause mortality, MACE, and MALE at 5 years using quartiles based on the distribution of the prediction score. RESULTS: Among 11,384 total patients, 4211 patients with DM met study criteria (mean age, 68.6 ± 11.9 years; 32.0% female). After allocating the training and validation subsets, the final test subset included 856 patients. During follow-up, there were 262 deaths, 319 MACE, and 99 MALE. Patients in the upper quartile of prediction based on deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.31-5.56), MACE (HR, 2.06; 95% CI, 1.49-2.91), and MALE (HR, 13.50; 95% CI, 5.83-31.27). CONCLUSIONS: An artificial intelligence enabled analysis of a resting Doppler arterial waveform permits identification of major adverse outcomes including all-cause mortality, MACE, and MALE among patients with DM.
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Peripheral Arterial Disease , Predictive Value of Tests , Ultrasonography, Doppler , Humans , Male , Female , Aged , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Peripheral Arterial Disease/complications , Risk Assessment , Middle Aged , Risk Factors , Deep Learning , Reproducibility of Results , Prognosis , Aged, 80 and over , Time Factors , Tibial Arteries/diagnostic imaging , Tibial Arteries/physiopathology , Diabetic Angiopathies/physiopathology , Diabetic Angiopathies/diagnostic imaging , Diabetic Angiopathies/mortality , Diabetic Angiopathies/diagnosisABSTRACT
Premortem clinical presentation of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE), therapy, and the clinal course is limited to case reports and small clinical series. An electronic search of Mayo Clinic records (03/31/2002-06/30/2022) with a subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE and active malignancy, excluding those with infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. In this retrospective cohort study, we analyzed 115 Ca-NBTE patients (mean age 63.2 ± 9.7 years, 66.1% female) involving 71 (61.7%) mitral, 58 (50.4%) aortic, 8 (6.9%) tricuspid, and 1 (0.9%) pulmonary valve. The most common cancer was lung (n = 45 cases (39.1%), followed by pancreatic (n = 19, 16.5%), gynecological (17, 14.8%), gastrointestinal (n = 10, 8.7%), and 10 (8.7%) with hematologic malignancy; 6 patients had two active cancers. Embolic complications at presentation were frequent: 94 (81.7%) brain, 11 splenic, 10 renal, 6 coronary, and 4 to the extremities. Of 104 anticoagulated patients, 60 received low molecular weight heparin, 17 unfractionated heparin, 16 apixaban, 8 warfarin, and 3 rivaroxaban. There were 18 arterial thromboembolisms; the Kaplan-Meier estimates of the incidence at 2 years were consistent with a rate of 15.9% [95% Confidence Interval (CI) 9.9-23.3], including 14 strokes (12.4%, 95%CI, 7.1-19.2), and 8 other arterial emboli (10.5%, 95%CI, 4.7-18.9); there were 10 venous thromboembolisms (8.9%, 95%CI, 4.5-15.0). Fourteen major bleedings occurred (12.8%, 95%CI, 7.3-19.9) and 94 patients died during follow-up (77.9%, 95%CI, 71.1-85.8). Ca-NBTE predominantly affected women with lung adenocarcinoma or digestive tract cancers and manifested by stroke with high mortality and frequent embolic and bleeding complications during anticoagulation therapy.
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Endocarditis, Non-Infective , Neoplasms , Humans , Female , Middle Aged , Male , Retrospective Studies , Aged , Endocarditis, Non-Infective/complications , Neoplasms/complications , Anticoagulants/therapeutic use , Pyrazoles/therapeutic use , Pancreatic Neoplasms/complications , Pyridones/therapeutic useSubject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products , Pulmonary Embolism , Humans , Risk AssessmentABSTRACT
BACKGROUND: Patients with peripheral artery disease are at increased risk for major adverse cardiac events, major adverse limb events, and all-cause death. Developing tools capable of identifying those patients with peripheral artery disease at greatest risk for major adverse events is the first step for outcome prevention. This study aimed to determine whether computer-assisted analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with peripheral artery disease at greatest risk for adverse outcome events. METHODS AND RESULTS: Consecutive patients (April 1, 2015, to December 31, 2020) undergoing ankle-brachial index testing were included. Patients were randomly allocated to training, validation, and testing subsets (60%/20%/20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict major adverse cardiac events, major adverse limb events, and all-cause death at 5 years. Patients were then analyzed in groups based on the quartiles of each prediction score in the training set. Among 11 384 total patients, 10 437 patients met study inclusion criteria (mean age, 65.8±14.8 years; 40.6% women). The test subset included 2084 patients. During 5 years of follow-up, there were 447 deaths, 585 major adverse cardiac events, and 161 MALE events. After adjusting for age, sex, and Charlson comorbidity index, deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 2.44 [95% CI, 1.78-3.34]), major adverse cardiac events (HR, 1.97 [95% CI, 1.49-2.61]), and major adverse limb events (HR, 11.03 [95% CI, 5.43-22.39]) at 5 years. CONCLUSIONS: An artificial intelligence-enabled analysis of Doppler arterial waveforms enables identification of major adverse outcomes among patients with peripheral artery disease, which may promote early adoption and adherence of risk factor modification.
Subject(s)
Artificial Intelligence , Peripheral Arterial Disease , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Peripheral Arterial Disease/diagnostic imaging , Risk FactorsABSTRACT
Background Published data on the risk of venous thromboembolism (VTE) with coronavirus disease 2019 (COVID-19) vaccines are scarce and inconclusive, leading to an unmet need for further studies. Methods A retrospective, multicentered study of adult patients vaccinated for one of the three approved COVID-19 vaccines in the United States of America and a pre-COVID-19 cohort of patients vaccinated for influenza at two institutions: Mayo Clinic Enterprise sites and the Medical College of Wisconsin, looking at rate of VTE over 90 days. VTE was identified by applying validated natural language processing algorithms to relevant imaging studies. Kaplan-Meier curves were used to evaluate rate of VTE and Cox proportional hazard models for incident VTE after vaccinations. Sensitivity analyses were performed for age, sex, outpatient versus inpatient status, and type of COVID-19 vaccine. Results A total of 911,381 study subjects received COVID-19 vaccine (mean age: 56.8 [standard deviation, SD: 18.3] years, 55.3% females) and 442,612 received influenza vaccine (mean age: 56.5 [SD: 18.3] years, 58.7% females). VTE occurred within 90 days in 1,498 (0.11%) of the total 1,353,993 vaccinations: 882 (0.10%) in the COVID-19 and 616 (0.14%) in the influenza vaccination cohort. After adjusting for confounding variables, there was no difference in VTE event rate after COVID-19 vaccination compared with influenza vaccination (adjusted hazard ratio: 0.95 [95% confidence interval: 0.85-1.05]). No significant difference in VTE rates was observed between the two cohorts on sensitivity analyses. Conclusion In this large cohort of COVID-19-vaccinated patients, risk of VTE at 90 days was low and no different than a pre-COVID-19 cohort of influenza-vaccinated patients.
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Importance: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored. Objectives: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting. Design, Setting, and Participants: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021. Exposures: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin. Main Outcomes and Measures: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs. Results: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs. Conclusions and Relevance: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.
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Neoplasms , Thrombosis , Venous Thromboembolism , Female , Male , Humans , Anticoagulants/therapeutic use , Warfarin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Venous Thromboembolism/etiology , Venous Thromboembolism/complications , Retrospective Studies , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Neoplasms/drug therapy , Thrombosis/complicationsABSTRACT
Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.
Subject(s)
COVID-19 , Thrombophilia , Venous Thromboembolism , Humans , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , COVID-19 Vaccines/adverse effects , COVID-19/complications , COVID-19/prevention & control , Thrombophilia/genetics , Vaccination/adverse effects , Risk Factors , Factor V/geneticsABSTRACT
BACKGROUND: Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. PATIENTS/METHODS: Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013-November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. RESULTS: This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16-2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41-2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05-1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08-2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00-1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46-0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45-0.84; p = 0.002) were associated with fewer major bleeding outcomes. CONCLUSION: Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.
Subject(s)
Neoplasms , Thrombosis , Venous Thromboembolism , Humans , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Anticoagulants/adverse effects , Hemorrhage/drug therapy , Thrombosis/drug therapy , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/chemically induced , RecurrenceABSTRACT
INTRODUCTION: The outcome of anticoagulation for cancer-associated venous thromboembolism (Ca-VTE) differs according to cancer location, but data are limited and inconsistent. MATERIALS AND METHODS: Patients with acute venous thromboembolism (VTE) enrolled between 03/01/2013 and 04/30/2021 were followed prospectively to assess VTE recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and death. RESULTS: There were 1702 (45.3 %) patients with Ca-VTE including: gastrointestinal (n = 340), pancreatic (n = 223), hematologic (n = 188), genitourinary (n = 163), lung (n = 139), ovarian (n = 109), breast (n = 97), renal (n = 75), prostate (n = 73), hepatobiliary (n = 70), brain (n = 57), and other cancers (n = 168); 2057 VTE patients had no cancer (NoCa-VTE). Hepatobiliary cancer had the highest VTE recurrence (all rates 100 person-years) of all cancers and higher compared to NoCa-VTE (13.69, p = 0.01), while the MB rate, although numerically higher (15.91), was not different (p = 0.09). Another 3 cancers had higher VTE recurrence but similar MB rates compared to NoCa-VTE: genitourinary [(9.59, p = 0.01) and (7.03, p = 1.0)], pancreatic [(9.74, p < 0.001) and (5.47, p = 1.00)], and hematologic [(5.29, p = 0.05) and (3.59, p = 1.0)]. Renal cancer had the highest rate of MB among all cancers and was higher than that of NoCa-VTE (16.49; p < 0.001), with no difference in VTE recurrence (1.62; p = 1.0). VTE recurrence and MB rates were not significantly different between NoCa-VTE and gastrointestinal, lung, breast, prostate, and brain cancers. CRNMB rates were similar and mortality higher in Ca-VTE patients, except for prostate and breast cancer, compared to NoCa-VTE. CONCLUSIONS: Significant differences in clinical outcomes indicate that anticoagulation strategies may need to be tailored to the primary cancer location.
Subject(s)
Neoplasms , Venous Thromboembolism , Male , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Anticoagulants/therapeutic use , Anticoagulants/pharmacology , Neoplasm Recurrence, Local , Blood Coagulation , Hemorrhage , Neoplasms/complications , Neoplasms/drug therapy , RecurrenceABSTRACT
BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.
Subject(s)
Neoplasms , Pulmonary Embolism , Venous Thromboembolism , Humans , Venous Thromboembolism/drug therapy , Anticoagulants/therapeutic use , Prospective Studies , Pulmonary Embolism/diagnosis , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Hemorrhage/diagnosis , Hemorrhage/epidemiology , Hemorrhage/etiology , Neoplasms/complications , Neoplasms/diagnosis , Neoplasms/epidemiology , RecurrenceABSTRACT
Aims: The non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE). Methods and results: We prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure - PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61-0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69-0.91; P ≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82-0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65-0.99; P = 0.003). Conclusion: Non-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.
ABSTRACT
BACKGROUND: Popliteal cysts (PC) result from distension of the gastrocnemio-semimembranosous bursa. Published reports indicate coincident PC and deep vein thrombosis (DVT). Whether the presence of PC increase the risk of deep vein thrombosis (DVT) remains unclear. METHODS: Lower extremity venous Duplex ultrasound (DUS) reports were evaluated across the Mayo Clinic Enterprise (Rochester, Minnesota, Jacksonville, Florida, Scottsdale, Arizona, and the Mayo Clinic Health System) in patients ≥ 18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute lower extremity DVT and PC from these reports. To determine whether there is a link between PC and lower extremity DVT, the frequency of PC among cases (ultrasounds with acute DVT) were compared to controls (ultrasounds without acute DVT). RESULTS: A total of 357,703 lower extremities venous DUS were performed in 237,052 patients (mean age 63.3 ± 16.6, 54.4% were female) between 1992 and 2021. Acute DVT was identified in 32,572 (9.1%) DUS, and PC in 32,448 (9.1%). PC were seen in a lower frequency (8.0%) of ultrasounds with acute DVT than those without (9.2%) acute DVT (OR: 0.85, 95% CI: 0.82 to 0.89, p < 0.001). In a multivariate logistic regression model after adjusting for age, sex, and race, PCs were not positively associated with acute DVT (adjusted OR: 0.84, 95% CI: 0.81 to 0.88). CONCLUSIONS: PC are an incidental finding or an alternative diagnosis on lower extremity venous DUS, a finding that increases significantly with age. PC were not a risk factor in the development of lower extremity DVT.
Subject(s)
Popliteal Cyst , Venous Thrombosis , Acute Disease , Female , Humans , Lower Extremity/blood supply , Male , Popliteal Cyst/complications , Popliteal Cyst/diagnostic imaging , Popliteal Vein/diagnostic imaging , Retrospective Studies , Risk Factors , Ultrasonography, Doppler, Duplex , Venous Thrombosis/complications , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/epidemiologyABSTRACT
BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. METHODS: Consecutive patients (4/8/2015 - 12/31/2020) undergoing rest and postexercise ankle-brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 - 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. RESULTS: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92-0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91-0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). CONCLUSION: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.
Subject(s)
Ankle Brachial Index , Peripheral Arterial Disease , Aged , Aged, 80 and over , Ankle Brachial Index/methods , Arteries , Artificial Intelligence , Humans , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Predictive Value of Tests , Ultrasonography, DopplerABSTRACT
It remains unexplored if the clinical picture and outcome of subsegmental pulmonary embolism (SSPE) differ between single versus multiple, and incidental versus symptomatic embolism. Consecutive patients anticoagulated for SSPE at the Mayo Thrombophilia Clinic (03/01/2013-12/31/2020) were followed forward to assess venous thromboembolism (VTE) recurrence, mortality, major bleeding, and clinically relevant non-major bleeding (CRNMB); expressed as a rate per 100 person-years. Among 3878 VTE patients, 1541 had pulmonary embolism including 224 (14.6%) with SSPE either single (n = 139) or multiple (n = 85; 46 bilateral and 39 unilateral emboli); 134 had incidental and 90 symptomatic SSPE. Patients with single were less often symptomatic and less often had coexisting DVT than multiple SSPE. Patients with incidental had a two-fold higher frequency of cancer compared to symptomatic SSPE. During the study period, 1 patient with single and 2 with multiple SSPE had VTE recurrence (rate of 1.14 vs 3.63, p = 0.280). Single SSPE patients experienced 2 episodes of major bleeding (rate of 2.36) while the multiple SSPE group had no major bleeding. Seven patients in each group had CRNMB events (rate of 8.20 vs 13.58 for single and multiple SSPE, respectively, p = 0.282). Patients with single SSPE had a higher death rate compared to multiple SSPE (43.07 vs 22.22, p = 0.031) but no difference was noted after adjusting for cancer (p = 0.388). Also, incidental had similar clinical outcomes to symptomatic SSPE.Interpretation Anticoagulated SSPE patients with single and multiple as well as incidental and symptomatic have a different clinical profile but similar clinical outcomes.
Subject(s)
Neoplasms , Pulmonary Embolism , Subacute Sclerosing Panencephalitis , Venous Thromboembolism , Anticoagulants , Hemorrhage , Humans , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapyABSTRACT
OBJECTIVE: To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT). METHODS: We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com. RESULTS: The results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I2, 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I2, 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding. CONCLUSION: DOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs. REGISTRATION: Open Science Framework (https://osf.io/dth86).