PDIA2 has a dual function in promoting androgen deprivation therapy induced venous thrombosis events and castrate resistant prostate cancer progression.

Androgen deprivation therapy (ADT) is the first line of treatment for metastatic prostate cancer (PCa) that effectively delays the tumor progression. However, it also increases the risk of venous thrombosis event (VTE) in patients, a leading cause of mortality. How a pro-thrombotic cascade is induced by ADT remains poorly understood. Here, we report that protein disulfide isomerase A2 (PDIA2) is upregulated in PCa cells to promote VTE formation and enhance PCa cells resistant to ADT. Using various in vitro and in vivo models, we demonstrated a dual function of PDIA2 that enhances tumor-mediated pro-coagulation activity via tumor-derived extracellular vehicles (EVs). It also stimulates PCa cell proliferation, colony formation, and xenograft growth androgen-independently. Mechanistically, PDIA2 activates the tissue factor (TF) on EVs through its isomerase activity, which subsequently triggers a pro-thrombotic cascade in the blood. Additionally, TF-containing EVs can activate the Src kinase inside PCa cells to enhance the AR signaling ligand independently. Androgen deprivation does not alter PDIA2 expression in PCa cells but enhances PDIA2 translocation to the cell membrane and EVs via suppressing the clathrin-dependent endocytic process. Co-recruitment of AR and FOXA1 to the PDIA2 promoter is required for PDIA2 transcription under androgen-deprived conditions. Importantly, blocking PDIA2 isomerase activity suppresses the pro-coagulation activity of patient plasma, PCa cell, and xenograft samples as well as castrate-resistant PCa xenograft growth. These results demonstrate that PDIA2 promotes VTE and tumor progression via activating TF from tumor-derived EVs. They rationalize pharmacological inhibition of PDIA2 to suppress ADT-induced VTE and castrate-resistant tumor progression.

Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-Enriched Rheumatoid Arthritis Patients.

OBJECTIVE: The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. METHODS: Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. RESULTS: Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. CONCLUSION: Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.

Superior mesenteric vein thrombosis due to COVID-19 vaccination: a case report.

BACKGROUND: The worldwide vaccination response to COVID-19 has been associated with rare thrombotic complications, including the case of postvaccination splanchnic venous thrombosis we report here. CASE PRESENTATION: An 80-year-old Japanese male with abdominal pain presented to our hospital six days after receiving a dose of the COVID-19 messenger ribonucleic acid vaccine. Abdominal computed tomography showed localized edema of the small intestine, increased density of the surrounding adipose tissue, and a thrombus in the superior mesenteric vein. Conservative inpatient treatment with unfractionated heparin relieved the thrombosis, and the patient is currently receiving oral apixaban as an outpatient. CONCLUSION: Reported cases of thrombosis after COVID-19 vaccination typically have been associated with viral vector vaccines, with few reports of thrombosis induced by mRNA vaccines. The potential for venous thrombosis should be explored when patients present with abdominal pain soon after COVID-19 vaccination.

Dose-response association of benzodiazepine use and development of deep vein thrombosis.

Benzodiazepines have sedative effects that cause reduced activity in users and may increase the risk of deep vein thrombosis. However, few studies have examined this potential risk of benzodiazepine use. This study examined the association between benzodiazepine use and the risk of deep vein thrombosis (DVT) in adults in Taiwan using a longitudinal health insurance database. The study population included 12,546 individuals with DVT and 50,184 matched controls. Results showed that benzodiazepine use was associated with an increased risk of DVT occurrence (adjusted odds ratio [aOR]: 1.66; 95 % CI, 1.54-1.79; P <0.001), with a dose-response relationship. Patients with a higher defined daily dose had a higher risk of DVT, with ORs of 1.65-, 2.09-, and 2.16-fold higher for those with an average benzodiazepine dose of <0.5, 0.5-0.9, or ≥1 (DDD/day), respectively, compared to nonbenzodiazepine users. Stratification by age, sex, and follow-up duration yielded similar results. This study highlights the need to evaluate the association and benefits of benzodiazepine prescription to decrease the risk of DVT development.

Should we add antiplatelet agents to current deep venous thrombosis treatments? A Cochrane Review summary with commentary.

BACKGROUND: Venous thromboembolism (VTE) is an important complication in rehabilitation practice despite preventive measures. The management can be complicated because patients may have co-existing cardiovascular comorbidities. OBJECTIVE: To assess the effects of antiplatelet agents in addition to current best medical practice (BMP) compared to current BMP (with or without placebo) for the treatment of deep venous thrombosis (DVT). METHODS: A summary of the Cochrane Review by Flumignan et al. (2022), with comments from a rehabilitation perspective. RESULTS: The review included six studies with 1625 eligible participants, with data up to 37.2 months of follow-up. When used after standard initial treatment with anticoagulants, antiplatelet agents such as aspirin in addition to BMP, may reduce recurrence of DVT or pulmonary embolism, when compared to BMP plus placebo in a chronic DVT setting and there may be a lower risk for post-thrombotic syndrome in patients with acute DVT. There is no clear difference in side effects, major bleeding, or pulmonary embolism (PE) with the use of antiplatelet agents. CONCLUSION: Adding antiplatelet agents to standard anticoagulation treatment in patients with VTE could provide benefit without increasing risks in selected patient groups. However, high quality studies with a long-term follow up are needed, including patients in rehabilitation settings.

Clinical outcomes in elderly atrial fibrillation patients at increased bleeding risk treated with very low dose vs. regular-dose non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.

AIMS: The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) [edoxaban 15 mg o.d., dabigatran 110 or 150 o.d., apixaban 2.5 mg o.d., or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or <10 mg o.d.] vs. regular-dosage (RD) NOACs (edoxaban 60/30 mg o.d. or other labeling-dosage NOACs) among a real-world cohort of elderly atrial fibrillation (AF) population similar to the ELDERCARE-AF cohort. METHODS AND RESULTS: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7294 and 4151 consecutive AF patients aged 80 years or older with a CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack (2 points) score ≥2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from 1 June 2012 to 31 December 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (31 December 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation [hazard ratio (HR): 1.54, 95% confidential interval (CI): 1.09-2.18; P = 0.014), venous thrombosis (HR: 3.75, 95% CI: 1.56-8.97; P = 0.003), and all-cause mortality (HR: 1.21, 95% CI: 1.15-1.29; P <0.001) compared with RD NOACs. VLD NOACs showed worse outcomes in most net clinical outcome (NCO) benefits. The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05). CONCLUSION: Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared with that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk.

Cerebral venous thrombosis after high-dose steroid in patient with multiple sclerosis: A case report.

RATIONALE: Multiple sclerosis (MS) is a central nervous system disease mainly mediated by immunity, which is one of the most common causes of neurological dysfunction in young people worldwide. In the acute phase, high-dose steroid therapy is effective. There are few reports about cerebral venous thrombosis (CVT) after high-dose steroid therapy. PATIENT CONCERNS: We present a case of a 19-year-old female diagnosed with MS who developed a headache after high-dose steroid therapy was diagnosed with CVT. Headache symptoms improved after anticoagulant treatment. DIAGNOSES: MS comorbid CVT. INTERVENTIONS: Anticoagulant therapy was added and hormone therapy was reduced. OUTCOMES: Clinical symptoms such as headache, limb numbness, and involuntary tremors in the right hand were improved, and the muscle strength of the right limb recovered to grade 4. The patient did not suffer from headaches after discharge and no abnormality in the computed tomography (CT) scan of the cephalic vein at the 5-months follow-up. LESSONS: High-dose steroid therapy may be a risk factor for CVT in patients with MS. MS patients who develop headaches during high-dose steroid therapy should undergo further cranial CTV to rule out CVT.

Investigating the risk of deep vein thrombosis with JAK inhibitors: a disproportionality analysis using FDA Adverse Event Reporting System Database (FAERS).

BACKGROUND: Janus kinase (JAK) inhibitors are immune-modulating medications used to treat conditions including rheumatoid arthritis, COVID-19, ulcerative colitis, atopic dermatitis, myelofibrosis, and polycythemia Vera. However, these medications have been associated with higher incidence of deep vein thrombosis. The objective of this study was to investigate potential safety signals for DVT associated with JAK inhibitors using disproportionality analysis from the FDA Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: The authors retrospectively investigated case/non-case analysis using Openvigil 2.1-MedDRA-v24 (2004Q1 to 2022Q4). The preferred term used was 'deep vein thrombosis,' and the drugs included were baricitinib, tofacitinib, and upadacitinib. Reporting odds ratio, proportional reporting ratio, and information component were used to detect signals. RESULTS: Overall 114,005 AE reports related to JAK inhibitors were identified, of which 647 reports (baricitinib - 169, tofacitinib - 425, and upadacitinib - 53) associated with DVT were obtained from FAERS. On analysis, baricitinib and tofacitinib had greater signal strength for age group of 65-100 years and all three had the highest signal strength for male gender. CONCLUSIONS: Our study identified signals for DVT with baricitinib, tofacitinib, and upadacitinib. Further research using well-designed epidemiological data is needed to validate these results.

Risk for recurrence of symptomatic upper-extremity deep vein thrombosis in patients without cancer: Analysis of three RIETE cohorts.

BACKGROUND: The natural history of patients with a pacemaker-related upper-extremity deep vein thrombosis (UEDVT) has not been consistently studied. METHODS: We used the RIETE registry data to compare the outcomes during anticoagulation and after its discontinuation in noncancer patients with symptomatic UEDVT associated with a pacemaker, other catheters, or no catheter. The major outcome was the composite of symptomatic pulmonary embolism or recurrent DVT. RESULTS: As of February 2022, 2578 patients with UEDVT were included: 156 had a pacemaker-related UEDVT, 557 had other catheters, and 1865 had no catheter. During anticoagulation, 61 patients (2.3%) developed recurrent VTE, 38 had major bleeding (1.4%), and 90 died (3.4%). After its discontinuation, 52 patients (4.4%) had recurrent acute venous thromboembolism (VTE) and six had major bleeding (0.5%). On multivariable analysis, there were no differences among subgroups in the rates of VTE recurrences or major bleeding during anticoagulation. After its discontinuation, patients with a pacemaker-related UEDVT had a higher risk for VTE recurrences than those with no catheter (adjusted OR: 4.59; 95% CI: 1.98-10.6). CONCLUSIONS: Patients with pacemaker-related UEDVT are at increased risk for VTE recurrences after discontinuing anticoagulation. If our findings are validated in adequately designed trials, this may justify changes in the current recommendations on the duration of anticoagulation.

Does use of long-term aspirin impact outcomes in patients with acute pancreatitis?

INTRODUCTION: Although the effect of rectal indomethacin in post-endoscopic retrograde cholangiopancreatography pancreatitis is well established, the effect of aspirin on acute pancreatitis (AP) is not well studied. We investigate the effect of aspirin on AP. METHODS: We collected data from the National Inpatient Sample database from 2016 to 2020, to identify adult patients with acute pancreatitis. Patients were stratified into 2 groups, based on the presence of aspirin use. The primary outcome was mortality, while other outcomes were sepsis, shock, acute kidney injury (AKI), ICU admission, deep venous thrombosis (DVT), pulmonary embolism (PE), portal vein thrombosis (PVT), pseudocyst and ileus. RESULTS: A total of 2.09 million patients met the inclusion criteria, of which 197 170 (9.41%) had long-term aspirin use. The majority of the patients with aspirin use were aged >65 years, male, White and had Medicare insurance. There was a higher incidence of biliary pancreatitis while rates of alcohol-induced pancreatitis were lower in patients with aspirin use. There was a lower incidence of mortality, sepsis, shock, PE, DVT, PVT and pseudocyst in patients with aspirin use. There was no difference in the incidence of ileus, while the incidence of AKI was higher. After adjusting for confounding factors, patients with aspirin use had a 23.6% lower risk of mortality. DISCUSSION: Our results reveal a significant finding of aspirin's protective effect on AP in the US population. Our study is the largest study revealing an association between aspirin and AP. Further studies assessing the role of aspirin use in AP are warranted.

Deep venous thrombosis and hyponatremia associated with citalopram use for behavioral symptoms in Parkinson's disease: a case report.

BACKGROUND: Evidence is limited regarding the optimal therapeutic approach for neuropsychiatric symptoms associated with Parkinson's disease dementia (PDD). Selective serotonin reuptake inhibitors (SSRIs) are widely used for mood disorders and behavioral symptoms in older adults with cognitive impairment, but they have limited efficacy in patients with PDD. The effect of SSRIs on hemostasis is also unclear. This report describes a patient with PDD who developed deep venous thrombosis (DVT) and hyponatremia after initiating citalopram treatment. CASE PRESENTATION: An 86-year-old woman with PDD presented to our emergency department with altered mental status, generalized weakness, and left lower leg swelling. Citalopram was begun 4 weeks previously for behavioral changes and was discontinued 2 days before presentation because of excessive fatigue. At presentation, her plasma sodium level was 123 mg/dL. Brain computed tomography showed age-related changes. Doppler ultrasound revealed a DVT in the left lower leg. The patient was treated with hypertonic saline and intravenous heparin. After normalization of her sodium, she was discharged on donepezil and apixaban. At follow-up, her sodium remained normal, and her cognition and behavior were noticeably improved. CONCLUSION: Older adults with Parkinson's disease are sensitive to adverse effects of psychotropic agents, including SSRIs, which are not recommended first-line agents for behavioral symptoms in PDD. Upon initiating SSRIs in older patients with functional decline and multiple comorbidities, physicians need to evaluate the patient's risk factors for bleeding or thrombosis. Physical activities should also be maintained as much as possible.

Long-term ambient air pollution and venous thromboembolism in a population-based Swedish cohort.

Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29 408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44-74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5 µg (PM2.5) and <10 µg (PM10), nitrogen oxides (NOx) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1-10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8 µg/m3 for PM2.5, 15.8 µg/m3 for PM10, 27.7 µg/m3 for NOx, and 0.96 µg/m3 for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01-1.37)) per interquartile range (IQR) of 1.2 µg/m3 increase in PM2.5 exposure. No significant associations were found between other pollutants or lag0 PM2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM2.5 was associated with increased risks of VTE in the general population in Sweden.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review.

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

External validation of the ADA score for predicting thrombosis among acutely ill hospitalized medical patients from the APEX Trial.

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism. The study endpoints included the composite of arterial or venous thrombosis and its components. Metrics of model calibration and discrimination were computed for assessing the performance of the ADA score as compared to the IMPROVE score, a well-validated VTE risk assessment model. Among 7,119 medical inpatients, 209 (2.9%) had a thrombosis event up to 77 days of follow-up. The ADA score demonstrated good calibration for both arterial and venous thrombosis, whereas the IMPROVE score had adequate calibration for venous thrombosis (p > 0.05 from the Hosmer-Lemeshow test). For discriminating arterial and venous thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.620 [95% CI: 0.582 to 0.657] vs. 0.590 [95% CI: 0.556 to 0.624]; ∆ c statistic = 0.030 [95% CI: -0.022 to 0.081]; p = 0.255). Similarly, for discriminating arterial thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.582 [95% CI: 0.534 to 0.629] vs. 0.609 [95% CI: 0.564 to 0.653]; ∆ c statistic = -0.027 [95% CI: -0.091 to 0.036]; p = 0.397). For discriminating venous thrombosis, the ADA score was modestly superior to the IMPROVE score (c statistic = 0.664 [95% CI: 0.607 to 0.722] vs. 0.573 [95% CI: 0.521 to 0.624]; ∆ c statistic = 0.091 [95% CI: 0.011 to 0.172]; p = 0.026). The ADA score had a higher sensitivity (0.579 [95% CI: 0.512 to 0.646]; vs. 0.440 [95% CI: 0.373 to 0.507]) but lower specificity (0.625 [95% CI: 0.614 to 0.637] vs. 0.747 [95% CI: 0.737 to 0.758]) than the IMPROVE score for predicting thrombosis. Among acutely ill hospitalized medical patients enrolled in the APEX trial, the ADA score demonstrated good calibration but suboptimal discrimination for predicting thrombosis. The findings support the use of either the ADA or IMPROVE score for thrombosis risk assessment. The applicability of the ADA score to non-COVID-19 populations warrants further research.Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Cerebral Venous Thrombosis With Topical Estrogen-Progesterone Use in a Young Heterosexual Male: A Case Report.

INTRODUCTION: Our report sheds light on the risk of topical hormonal use in relation to cerebral venous sinus thrombosis. We diagnosed our patient with cerebral venous thrombosis (CVT) using computed tomography venogram, then detailed history and examination were obtained, and thorough blood tests and imaging were done to exclude other causes of CVT like thrombophilias, infections, and malignancies. CASE REPORT: Our patient is a 37-year-old heterosexual male, presented with headache only. The computed tomography venogram showed extensive CVT in the right internal jugular vein, sigmoid, transverse, and straight cerebral venous; detailed history and investigations suggest that his use of crushed oral contraceptive pills mixed with water topically on the scalp is the most important predisposing factor. This patient was managed with anticoagulants and is being followed in the clinic. CONCLUSION: Oral hormonal use in contraceptives is a known risk factor for CVT. This case sheds light on the importance of topical hormonal use concerning CVT in females and males; it stresses the need for more studies in that area, as it is poorly studied.

Acute Portal and Superior Mesenteric Vein Thrombosis with Topical Testosterone Therapy: An Adverse Drug Event Case Report.

This is a case report of a 55-year-old Caucasian male prescribed topical testosterone therapy for 12 months prior to admission, when he was diagnosed with acute thrombosis in the portal vein (PVT) and superior mesenteric vein (SMV). The patient had a negative thrombophilia workup, including Factor V Leiden, Prothrombin G20210A, and JAK2 V617F mutations. There were no other pertinent laboratory markers that raised concern for the cause of thrombus. No strong familial history of venous thromboembolism (VTE) was reported during the patient's initial workup. With this in mind, the patient's use of topical testosterone therapy was considered the most likely risk factor for the PVT and SMV thrombus. During hospitalization, the patient was initiated on therapeutic anticoagulation with a heparin drip and discharged to home on apixaban for 3 months with extended therapy to be determined by outpatient hematologist. With no other identified VTE risk factors, probability that this patient's VTE was attributed to testosterone was evaluated using the Naranjo scale with a calculated score of 6, which classifies the adverse reaction as "likely." Clinicians should be aware of the possibility that topical testosterone therapy may be a risk factor for venous thrombosis in unusual sites.

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial.

OBJECTIVE: To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT). DESIGN: Randomised, double blind, placebo controlled clinical trial. SETTING: 28 outpatient clinics specialising in venous thromboembolism. PARTICIPANTS: 402 adults (≥18 years) with symptomatic isolated distal DVT. INTERVENTIONS: After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion. MAIN OUTCOMES MEASURES: The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes. RESULTS: 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred. CONCLUSIONS: Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. TRIAL REGISTRATION: EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.

Apixaban vs Enoxaparin for Post-Surgical Extended-Duration Venous Thromboembolic Event Prophylaxis: A Prospective Quality Improvement Study.

PURPOSE: Venous thromboembolic events (VTEs) are a major cause of morbidity following abdominopelvic oncologic surgery. Enoxaparin, a subcutaneous injectable low molecular weight heparin, is commonly used for extended-duration VTE prophylaxis (EP), but has been associated with noncompliance. Newer direct oral anticoagulants have not been prospectively studied in the urologic oncology post-discharge setting. We aimed to improve compliance with EP following abdominopelvic oncologic surgery and secondarily test the hypothesis that apixaban is noninferior to enoxaparin for EP. MATERIALS AND METHODS: A single-center prospective quality improvement study measuring patient compliance and safety with EP was conducted between August 10, 2020 and September 21, 2021. Baseline data were continuously collected for 6 months, followed by a uniform departmental change from enoxaparin to apixaban. The duration of data collection was determined a priori using a noninferiority sample size estimation (145 per group). The primary outcome was compliance events (real or potential barriers to EP use). The secondary outcome was 30-day post-discharge safety events (symptomatic VTE or major bleed). RESULTS: A total of 161 patients were discharged with enoxaparin (baseline period) and 154 with apixaban (intervention period). Safety events occurred in 3.1% vs 0% of patients receiving enoxaparin and apixaban, respectively. The absolute risk difference of 3.1% (95% CI: 0.043%-5.8%) met the prespecified noninferiority threshold (p=0.028 for apixaban superiority). Compliance events occurred in 33.5% of enoxaparin patients and 14.3% of apixaban patients (p=0.0001). CONCLUSIONS: There were fewer compliance events using apixaban for EP than enoxaparin after urologic oncology surgery. Regarding safety, apixaban is noninferior to enoxaparin and may in fact have fewer associated major complications.

Edoxaban: front-line treatment for brachiocephalic vein thrombosis in primitive mediastinal seminoma: A case report and literature review.

RATIONALE: Venous thromboembolism is a feared frequent complication of cancer with a 2-way relationship. Low molecular weight heparin is the mainstay of treatment. The use of direct oral anticoagulants is supported by established evidence for the treatment of deep vein thrombosis also in active cancer and they are prioritized over low molecular weight heparin for cancer-associated thrombosis according to current guidelines. However, upper limb deep vein thrombosis is poorly studied with scant data on the use of direct oral anticoagulants in noncatheter-related deep vein thrombosis. We report the case of a patient with noncatheter-related deep vein thrombosis and a rare tumor site effectively and safely treated with a direct oral anticoagulant, edoxaban, after lack of efficacy with low molecular weight heparin. PATIENT CONCERNS: A 35-year-old man with primitive mediastinal seminoma presented at our Cardio-Oncology Unit for prechemotherapy assessment. DIAGNOSIS: Persistent brachiocephalic deep vein thrombosis, despite full-dose enoxaparin, was detected at ultrasonography. INTERVENTION: We decided to switch the anticoagulant treatment from enoxaparin to edoxaban. OUTCOME: The 3-month ultrasonography showed almost total regression of the deep vein thrombosis without any adverse effects and a good patient compliance. LESSONS: We conducted a literature review on upper limb deep vein thrombosis, since its management is challenging due to inconsistency of evidence. This report highlights the benefits of direct oral anticoagulants compared to low molecular weight heparins in cancer-associated thrombosis therapy in terms of efficacy, safety and ease of use.