Daniels, Paul R.

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.

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.

Background Guidelines promote shared decision‐making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within‐encounter SDM tool to usual care (UC) increases patient involvement in decision‐making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. Methods and Results We conducted a multicenter, encounter‐level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow‐up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. Conclusions In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: clinicaltrials.gov. Identifier: NCT02905032.

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.

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.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m 2 ), obese (30–39.9 kg/m 2 ), and morbidly obese (⩾ 40 kg/m 2 ). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82–1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62–1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Introduction Safe management of warfarin in the inpatient setting can be challenging. At the Mayo Clinic hospitals in Rochester, Minnesota, we set out to improve the safety of warfarin management among surgical and non-surgical inpatients. Methods A multidisciplinary team designed a pharmacist-managed warfarin protocol (PMWP) which designated warfarin dosing to inpatient pharmacists with guidance from computerised dosing algorithms. Ordering this protocol was ultimately designed as an ‘opt out’ practice. The primary improvement measure was frequency of international normalised ratio (INR) greater than 5; secondary measures included adoption rate of the protocol, a counterbalance INR metric (INR <1.7 three days after first inpatient warfarin dose), and complication rates, including bleeding and thrombosis events. An interrupted time series analysis was conducted to compare outcomes. Results Among over 50 000 inpatient warfarin recipients, the PMWP was adopted for the majority of both surgical and non-surgical inpatients during the study period (1 January 2005 to 31 December 2011). The primary improvement measure decreased from 5.6% to 3.4% for medical patients and from 5.2% to 2.4% for surgical patients during the preimplementation and postimplementation periods, respectively. The INR counterbalance measure did not change. Postoperative bleeding decreased from 13.5% to 11.1% among surgical patients, but bleeding was unchanged among medical patients. Conclusion Our PMWP led to achievement of improved INR control for inpatient warfarin recipients and to less near-term bleeding among higher risk, surgical patients.