Wysokiński, Waldemar E.

Background: Active malignancy accounts for 20% of venous thromboembolism (VTE) in the community and is the second leading cause of death among cancer patients. Rivaroxaban offers a convenient alternative to conventional anticoagulation for VTE in cancer patients but its efficacy and safety for this group of patients is not well documented. Patients and Methods: All patients with cancer-associated deep vein thrombosis (DVT) or pulmonary embolism (PE), enrolled into Mayo Rochester Thrombophilia Clinic Direct Oral Anticoagulants Registry between November 1, 2012 and April 30, 2015, were followed prospectively to provide an estimate of the efficacy and safety of this form of therapy. Follow up was obtained in person or by mailed or telephone survey. Results: Out of the 377 patients in the registry, 118 (31%) patients (51% female, mean age 66±10 years) had active malignancy related VTE (62% DVT, 24% PE, and 14% DVT/PE) treated with rivaroxaban. The most common malignancies in this group were: gastrointestinal (20%), lung (13%) and ovary/uterine (13%). Over the follow up period, the VTE recurrence rate was 3.3% (2 DVT and 2 PE; of these, 2 occurred during periprocedural interruptions of anticoagulation); and the major bleeding rate was 3%. There were 26 deaths (22%), none related to VTE or bleeding. The main reasons for choosing rivaroxaban were lower cost compared to LMWH, no need for injections, and the lack of food/drug interactions. Conclusions: These data support that rivaroxaban may provide a safe, effective, and convenient alternative treatment option to standard therapy for cancer related VTE treatment.

Background: Testicular vein thrombosis (TVT) is not currently well-described in the literature. A better understanding of the natural history of TVT will allow for development of optimal management strategies for this little known entity. Methods: The goal of this project was to compare TVT with ovarian vein thrombosis (OVT) and lower extremity deep vein thrombosis (DVT). Patients with TVT, OVT, or DVT between 1995 and 2015 were identified and a chart review was performed. Results: A total of 39 patients with TVT occurring between 1995 and 2015 were identified and compared with 35 patients with OVT and 114 randomly chosen DVT patients. Mean duration of follow-up was 2.9 years (range 0-16.1). Patient demographics can be seen in table 1. Cancer-related (p-value=<0.0001) and idiopathic thrombosis (p-value=0.01) rates were significantly different among the groups. Recurrence rates were similar between TVT and OVT (4.2 vs. 3 per 100 patient-years, p-value = 0.9) as well as TVT and DVT (4.2 vs 2.2 recurrences per 100 patient-years, p-value= 0.37). There were 25 deaths (22%) in DVT patients, 9 (26%) in OVT patients, and 12 (31%) in TVT patients (p-value= 0.541). There was one major bleeding event in both an OVT patient and a TVT patient. Conclusion: Etiology of TVT differs from that of OVT and DVT, specifically in cancer-related and idiopathic thrombosis rate. Our data supports a similar rate of recurrent venous thromboembolism and death in TVT as compared with DVT and OVT.

Abstract The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P &lt; .001) and unilateral (P &lt; .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

Background:There is limited published data on the association between malignancy and the location of venous thromboembolism (VTE) in the body. Aims:Assess the location of VTE in the body in patients with active cancer and compare these results in patients without malignancy. Methods:Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013 and November 30, 2019 for acute VTE were followed prospectively. Anatomical site of thrombosis and malignancy status were recorded. Patient outcomes were assessed in person, by mailed questionnaire, or by a scripted phone interview. Active cancer was defined as treatment for malignancy within the last six months or not yet in remission. Results:During the study period there were 2,798 patients with acute VTE (1256 with and 1542 without active cancer). Pulmonary emboli were more common in patients with active cancer compared to patients without cancer (49.5% vs. 39.7%, p&lt;0.001). Upper extremity deep vein thrombosis (11.4 % vs. 7.7%, p&lt;0.001), renal vein thrombi (1.4% vs. 0.2%, p&lt;0.001) and splanchnic vein thrombi (9.3% vs. 6.0%, p=0.001) were all more common in patients with active cancer compared to patients without cancer. Conclusion:Compared to those without malignancy, patients with active cancer were more likely to have pulmonary emboli, upper extremity deep vein thrombosis, renal vein thrombi, and splanchnic vein thrombi. Disclosures No relevant conflicts of interest to declare.

Background: Popliteal fossa cysts (PFCs aka Baker's cysts) are synovial cysts of the knee joint that can be symptomatic or asymptomatic and incidentally identified on ultrasound. Whether PFCs are associated with deep vein thrombosis (DVT) is unknown. Possible mechanisms for an association include direct compression of the popliteal vein, indirect compression on the popliteal vein with leg flexion, adjacent inflammation of the cyst, or relative immobility due to underlying joint disease itself. Methods: Lower extremity venous Duplex ultrasound radiology reports from the inception of electronic archiving through 11/14/2019 were evaluated across the Mayo Clinic Enterprise (Rochester MN, Jacksonville, FL, Scottsdale AZ, and Mayo Clinic Health System) in patients &gt;18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute DVT (proximal or distal) and PFCs. A random sample of 1,752 ultrasound reports underwent manual review to calculate the sensitivity and specificity of the NLP algorithm. Cases (ultrasounds with acute DVT) were compared to controls (ultrasound without acute DVT) to examine the frequency of PFCs. IRB approval was obtained and patients lacking Minnesota research authorization were excluded. Results: A total of 332,016 lower extremity venous ultrasounds were performed in 223,035 patients; 156,846 unilateral and 175,170 bilateral lower extremities exams. The mean age at ultrasound was 63.3 (SD 16.5) and 54.7% were female. Ultrasound reports were available for analysis starting in 1992 with a significant increase in the number of ultrasounds performed over the study period across the enterprise (Figure 1). Overall, acute DVT was identified in 24,179 (7.3%) of ultrasounds, and PFCs were identified in 32,427 (9.8%) of ultrasounds. The sensitivity and specificity of the NLP algorithm in the full dataset to identify acute DVT was 86.0% and 97.2%, respectfully. The sensitivity and specificity of the NLP algorithm to identify PFCs was 97.8% and 99.5%, respectively. PFCs were present in 9.3% of ultrasounds with acute DVT and 9.8% of ultrasounds without acute DVT (p=0.007), OR 0.94 (95% CI 0.90-0.98). In a multivariate logistic regression model, after adjusting for age and sex, results remained significant (aOR 0.95, 95% CI 0.91-0.995). Comparing ultrasounds before and after 2010, there was a higher percentage of PFCs and acute DVT reported after 2010 (p&lt;0.001 for both). Sensitivity analyses comparing results before or after 2010, by sex, and only in the first ultrasound performed per person, demonstrated similar results. Conclusions: PFCs are negatively associated with the presence of acute DVT on lower extremity venous Duplex ultrasound. This data does not support PFCs as a contributing or causative factor in the development of lower extremity DVT. Figure 1 Disclosures No relevant conflicts of interest to declare.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

Abstract Background The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. Methods Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016–August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. Results Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). Conclusion Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.

Abstract 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.

BACKGROUND/OBJECTVES Four direct‐acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). METHODS Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta‐analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel‐Haenszel relative risk (RR) random effects model was used to pool results across studies. RESULTS Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow‐up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38‐.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56‐1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. CONCLUSION In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE‐related deaths compared with VKAs with similar bleeding outcomes.

AbstractRandomized 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.