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ABSTRACT: Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.

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Background: Patients with suspected or newly diagnosed venous thromboembolism (VTE) are often referred to the emergency department (ED) for management, where anticoagulation is initiated. However, when the patient is judged to be suitable for outpatient management, counseling and follow-up specialty care are frequently suboptimal. Objectives: To establish an advanced practice provider (APP)-led rapid follow-up clinic to improve transitions of care for patients with newly diagnosed deep vein thrombosis or low-risk pulmonary embolism and to provide continued specialty care and support, including management of complications and medication access issues. Methods: In order to address this gap in transition of care, we developed an APP-led clinic with a mandate to improve quality and safety in the outpatient setting for patients with acute VTE. Results: In the first 2 years, a total of 234 patients were evaluated, of whom data were standardized and reviewed for 229. Utilization steadily increased over time, with at least 10% of patients requiring financial medication assistance over both years. Seventy-two percent of patients were referred from the ED in the first year and 59% in the second year, and referrals from non-ED outpatient specialties increased. Data on deviations from standard care identified in referred patients were collected in the second year and found in 19 (12.7%) of cases. These included unnecessarily prescribed or changed anticoagulants, dosing errors, misclassification of thrombosis, and other deviations. Patient demographic data also demonstrated increasing diversity of the patient population over time, with increased utilization by Hispanic and African American patients in the second year. This highlighted the need for better patient education material translations into Spanish, which is a future aim. Conclusion: In summary, the APP-led VTE Transition Clinic was feasible and grew quickly in utilization, diversity of referrals, and diversity of patients served.

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Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

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ABSTRACT: Livedoid vasculopathy (LV) is an ulcerative disorder of the lower extremities characterized by dermal vessel thrombosis with unclear cause. Recent reports of LV-associated upper extremity peripheral neuropathy and epineurial thrombosis suggest a systemic etiology for the condition. We sought to outline the characteristics of peripheral neuropathy in patients with LV. Cases of LV with concurrent peripheral neuropathy and reviewable electrodiagnostic testing reports were identified by electronic medical record database query and examined in detail. Of 53 patients with LV, 33 (62%) had peripheral neuropathy, 11 had reviewable electrodiagnostic reports, and 6 had no clear alternative explanation for neuropathy. Distal symmetric polyneuropathy was the most commonly observed pattern of neuropathy (n = 3) followed by mononeuropathy multiplex (n = 2). Most patients experienced symptoms in both upper and lower extremities (n = 4). Peripheral neuropathy is common in patients with LV. Whether this association is reflective of a systemic, prothrombotic etiology remains to be determined.

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In clinical practice, direct oral anticoagulants (DOACs) are increasingly used for venous thromboembolism treatment and prevention. A substantial proportion of patients with venous thromboembolism are also obese. International guidance published in 2016 stated that DOACs could be used in standard doses in patients with obesity up to a body mass index (BMI) of 40 kg/m2, but should not be used in those with severe obesity (BMI >40 kg/m2) owing to limited supporting data at the time. Although updated guidance in 2021 removed this limitation, some health care providers still avoid DOACs even in patients with lower levels of obesity. Furthermore, there are still evidence gaps regarding treatment of severe obesity, the role of peak and trough DOAC levels in these patients, use of DOACs after bariatric surgery, and appropriateness of DOAC dose reduction in the setting of secondary venous thromboembolism prevention. This document describes proceedings and outcomes of a multidisciplinary panel convened to review these and other key issues regarding DOAC use for treatment or prevention of venous thromboembolism in individuals with obesity.

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Laparoscopic sleeve gastrectomy (LSG) is an effective weight-loss operation. Portomesenteric vein thrombosis (PMVT) is an important complication of LSG. We identified four cases of PMVT after LSG at our institution in women aged 36-47 with BMIs ranging from 44-48 kg/m2. All presented 8-19 days postoperatively. Common symptoms were nausea, vomiting, and abdominal pain. Thrombotic risk factors were previous deep vein thrombosis and oral contraceptive use. Management included therapeutic anti-coagulation, directed thrombolysis, and surgery. Complications were readmission, bowel resection, and bleeding. Discharge recommendations ranged from 3-6 months of anticoagulation using various anticoagulants. No consensus was reached on post-treatment hypercoagulable work up or imaging. All cases required multi-disciplinary approach with Surgery, Interventional Radiology, and Hematology. As PMVT is a rare but potentially morbid complication of LSG, further development of tools that quantify preoperative thrombotic risk and clear guidance regarding use of anticoagulants are needed for prevention and treatment of PMVT following LSG.

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Livedoid vasculopathy (LV) is a rare thrombotic vasculopathy of the dermis characterized by painful, relapsing ulcers over the lower extremities. Diagnosis is challenging due to the overlap in clinical appearance and nomenclature with other skin disorders. Treatment selection is complicated by poor understanding of the pathogenesis of LV and lack of robust clinical trials evaluating therapy efficacy. The terminology and pathophysiology of LV are reviewed here, along with its epidemiology, clinical and histologic features, and treatment options. A diagnostic pathway is suggested to guide providers in evaluating for comorbidities, referring to appropriate specialists, and choosing from the available classes of therapy.

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Population pharmacokinetic (PK)/pharmacodynamic models are commonly used to inform drug dosing; however, often real-world patients are not well represented in the clinical trial population. We sought to determine how well dosing recommended in the rivaroxaban drug label results in exposure for real-world patients within a reference area under the concentration-time curve (AUC) range. To accomplish this, we assessed the utility of a prior published rivaroxaban population PK model to predict exposure in real-world patients. We used the model to predict rivaroxaban exposure for 230 real-world patients using 3 methods: (1) using patient phenotype information only, (2) using individual post hoc estimates of clearance from the prior model based on single PK samples of rivaroxaban collected at steady state without refitting of the prior model, and (3) using individual post hoc estimates of clearance from the prior model based on PK samples of rivaroxaban collected at steady state after refitting of the prior model. We compared the results across 3 software packages (NONMEM, Phoenix NLME, and Monolix). We found that while the average patient-assigned dosing per the drug label will likely result in the AUC falling within the reference range, AUC for most individual patients will be outside the reference range. When comparing post hoc estimates, the average pairwise percentage differences were all <10% when comparing the software packages, but individual pairwise estimates varied as much as 50%. This study demonstrates the use of a prior published rivaroxaban population PK model to predict exposure in real-world patients.

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BACKGROUND: Thrombosis of the left internal jugular vein in an astronaut aboard the International Space Station was recently described, incidentally discovered during a research study of blood flow in neck veins in microgravity. Given this event, and the high incidence of flow abnormalities, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thrombosis. METHODS: Duplex ultrasound of the bilateral internal jugular veins was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory maneuvers were performed. Images were analyzed for thrombosis and certain hemodynamic characteristics, including peak velocity and degree of echogenicity. RESULTS: Eleven astronauts were evaluated with matching terrestrial and in-flight ultrasounds. No thrombosis was detected. Compared to terrestrial ultrasound measurements, in-flight peak velocity was reduced and lowest in the left. Six of 11 astronauts had mild-moderate echogenicity in the left internal jugular vein during spaceflight, but none had more than mild echogenicity in the right internal jugular vein. Two astronauts developed retrograde blood flow in the left internal jugular vein. CONCLUSION: Abnormal flow characteristics in microgravity, most prominent in the left internal jugular vein, may signal an increased risk for thrombus formation in some individuals.

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