Pulmonary vein thrombosis: Clinical presentation and outcomes.

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.

Reduced calf muscle pump function is not explained by handgrip strength measurements.

OBJECTIVE: Reduced calf muscle pump function (CPF) is an independent risk factor for venous thromboembolism and mortality. We aimed to evaluate the relationship between handgrip strength (HGS) and CPF. METHODS: Patients referred to the Gonda Vascular Laboratory for noninvasive venous studies were identified and consented. Patients underwent standard venous air plethysmography protocol. CPF (ejection fraction) was measured in each lower extremity of ambulatory patients by comparing refill volume after ankle flexes and passive refill volumes. The cutoff for reduced CPF (rCPF) was defined as an ejection fraction of <45%. Maximum HGS bilaterally was obtained (three trials per hand) using a dynamometer. HGS and CPF were compared (right hand to calf, left hand to calf) and the correlation between the measures was evaluated. RESULTS: 115 patients (mean age, 59.2 ± 17.4 years; 67 females, mean body mass index, 30.83 ± 6.46) were consented and assessed for HGS and CPF. rCPF was observed in 53 right legs (46%) and 67 left legs (58%). CPF was reduced bilaterally in 45 (39%) and unilaterally in 30 (26%) patients. HGS was reduced bilaterally in 74 (64.3%), unilaterally in 23 (20%), and normal in 18 (15.7%) patients. Comparing each hand/calf pair, no significant correlations were seen between HGS and CPF. The Spearman's rank correlation coefficients test yielded values of 0.16 for the right side and 0.10 for the left side. CONCLUSIONS: There is no significant correlation between HGS and CPF, demonstrating that HGS measurements are not an acceptable surrogate for rCPF, indicating different pathophysiological mechanisms for each process.

Artificial intelligence of arterial Doppler waveforms to predict major adverse outcomes among patients with diabetes mellitus.

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.

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis.

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.

Influence of primary cancer site on clinical outcomes of anticoagulation for associated venous thromboembolism.

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.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

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.

Popliteal cysts are not a risk factor for lower extremity deep vein thrombosis.

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.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

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.

Single versus multiple and incidental versus symptomatic subsegmental pulmonary embolism: clinical characteristics and outcome.

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.

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban, Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism.

OBJECTIVE: To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE). PATIENTS AND METHODS: Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB). RESULTS: In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37). CONCLUSION: Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03504007.

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19-Positive Compared With COVID-19-Negative Patients.

OBJECTIVE: To determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)-positive compared with COVID-19-negative patients. PATIENTS AND METHODS: Adult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list. RESULTS: We identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive-patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death. CONCLUSION: Early experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.

Risk of pulmonary emboli after removal of an upper extremity central catheter associated with a deep vein thrombosis.

Standard treatment of catheter-associated upper extremity deep vein thrombosis (UE-DVT) is anticoagulation, although catheters are often removed for this indication. The optimal time for catheter removal and whether the act and/or timing of catheter removal is associated with pulmonary embolism (PE) remain unknown. A retrospective cohort study was performed at 8 participating institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies and central venous catheter (CVC)-associated UE-DVT were included from 1 January 2010 through 31 December 2016. The primary outcome was objectively confirmed PE within 7 days of UE-DVT diagnosis in anticoagulated patients comparing early (≤48 hours) vs delayed (>48 hours) catheter removal. A total of 626 patients were included, among whom 480 were treated with anticoagulation. Among anticoagulated patients, 255 underwent early CVC removal, while 225 had delayed or no CVC removal; 146 patients received no anticoagulation, among whom 116 underwent CVC removal alone. PE within 7 days occurred in 2 patients (0.78%) with early removal compared with 1 patient (0.44%) with delayed or no CVC removal (P > .9). PE or any cause of death within 7 days occurred in 3 patients in both the early removal (1.18%) and delayed/no removal (1.33%) groups (P > .9). In patients treated with CVC removal only (no anticoagulation), there were no PEs but 3 deaths within 7 days. In patients with hematological malignancy and CVC-associated UE-DVT, early removal of CVCs was not associated with an increased risk of PE compared with delayed or no removal.

Delayed anticoagulation in venous thromboembolism: Reasons and associated outcomes.

OBJECTIVE: We assessed the number of cases with delayed anticoagulation initiation, explored the reasons for the delay, and its impact on outcome in patients with acute venous thromboembolism (VTE) treated in an organized setting of treatment initiation and continuous, prospective follow-up. METHODS: Patients with anticoagulation initiation delay >24 hours were identified within the cohort of patients with acute VTE enrolled in the Mayo Clinic Venous Thromboembolism Registry between 2013 and 2020. The reasons for treatment delay were explored by reviewing the electronic database. VTE recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared to those with no anticoagulation delay. RESULTS: Of 2378 patients with acute VTE, 100 (4.2%) experienced an anticoagulation delay. We identified seven reasons for treatment delays: deferring anticoagulation initiation to specialists (n = 38), thrombocytopenia (n = 10), planned or recent procedure (n = 16), active or recent bleeding (n = 12), missed diagnosis (n = 7), logistics (n = 6), and patient decision (n = 4). In seven cases, no reason was identified. We identified modifiable reasons for anticoagulation delay in 55%. At 90-day follow-up, patients with anticoagulation delay had a higher rate of mortality and major bleeding. VTE recurrence and CRNMB were not statistically different compared to those without anticoagulation delay. After adjustment for age, weight, and cancer, hazard ratios (HRs) for VTE recurrence and major bleeding remained elevated but not to a statistically significant level. CONCLUSION: In the setting of a highly organized system of anticoagulation initiation, the incidence of treatment delay is low. Yet most delays could be avoided. A low number of cases provide insufficient power to evaluate the clinical consequences of anticoagulation initiation delay; however, elevated HR for VTE recurrence and major bleeding suggest association and need for further investigation.

Treatment of catheter-related thrombosis in patients with hematologic malignancies: A Venous thromboEmbolism Network U.S. retrospective cohort study.

INTRODUCTION: Optimal treatment of catheter-related thrombosis (CRT) is uncertain in patients with hematologic malignancy. We aimed to evaluate the treatment strategies, outcomes, and predictors of recurrent venous thromboembolism (VTE) associated with catheter-related thrombosis (CRT) in patients with hematologic malignancy. METHODS: We performed a multicenter retrospective cohort study of eight institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies with documented CRT were identified using ICD-9 and ICD-10 diagnostic codes. Semi-competing risks proportional hazard regression models were created. RESULTS AND CONCLUSIONS: Of the 663 patients in the cohort, 124 (19%) were treated with anticoagulation alone, 388 (58%) were treated with anticoagulation and catheter removal, 119 (18%) treated with catheter removal only, and 32 (5%) had neither catheter removal nor anticoagulation. 100 (15%) patients experienced a recurrent VTE event. In the 579 patients who had catheter removal, the most common reason for catheter removal was the CRT [392 (68%)]. For subjects who received any anticoagulation (n = 512), total anticoagulation duration was not associated with VTE recurrence [1.000 (0.999-1.002)]. After adjustment patients treated with catheter removal only had an increased risk of VTE recurrence [2.50 (1.24-5.07)] and death [4.96 (2.47-9.97)]. Patients with no treatment had increased risk of death [16.81 (6.22-45.38)] and death after VTE recurrence [27.29 (3.13-238.13)]. In this large, multicenter retrospective cohort, we found significant variability in the treatment of CRT in patients with hematologic malignancy. Treatment without anticoagulation was associated with recurrent VTE.

Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients.

OBJECTIVE: To evaluate differences in thromboinflammatory biomarkers between patients with severe coronavirus disease 2019 (COVID-19) infection/death and mild infection. PATIENTS AND METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing thromboinflammatory biomarkers in COVID-19 among patients with severe COVID-19 disease or death (severe/nonsurvivors) and those with nonsevere disease or survivors (nonsevere/survivors) from January 1, 2020, through July 11, 2020. Inclusion criteria were (1) hospitalized patients 18 years or older comparing severe/nonsurvivors vs nonsevere/survivors and (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the 2 groups of COVID-19 severity. RESULTS: We included 75 studies with 17,052 patients. The severe/nonsurvivor group was older, had a greater proportion of men, and had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and chronic obstructive pulmonary disease. Thromboinflammatory biomarkers were significantly higher in patients with severe disease, including D-dimer (WMD, 0.60; 95% CI, 0.49 to 0.71; I 2 =83.85%), fibrinogen (WMD, 0.42; 95% CI, 0.18 to 0.67; I 2 =61.88%; P<.001), C-reactive protein (CRP) (WMD, 35.74; 95% CI, 30.16 to 41.31; I 2 =85.27%), high-sensitivity CRP (WMD, 62.68; 95% CI, 45.27 to 80.09; I 2 =0%), interleukin 6 (WMD, 22.81; 95% CI, 17.90 to 27.72; I 2 =90.42%), and ferritin (WMD, 506.15; 95% CI, 356.24 to 656.06; I 2 =52.02%). Moderate to significant heterogeneity was observed for all parameters (I 2 > 25%). Subanalysis based on disease severity, mortality, and geographic region of the studies revealed similar inferences. CONCLUSION: Thromboinflammatory biomarkers (D-dimer, fibrinogen, CRP, high-sensitivity CRP, ferritin, and interleukin 6) and marker of end-organ damage (high-sensitivity troponin I) are associated with increased severity and mortality in COVID-19 infection.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism.

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome. METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories. RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category. CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial.

BACKGROUND: Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data support its use in cancer patients. OBJECTIVES: The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding (CRNMB). PATIENTS/METHODS: Patients with cancer-associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily). RESULTS: Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin [P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group]. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients [HR 0.099, 95% confidence interval [CI], 0.013-0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups. CONCLUSIONS: Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.