Characteristics and Management of Patients With Cancer and Atrial Fibrillation: The BLITZ-AF Cancer Registry.

Background: Atrial fibrillation (AF) is a frequent cardiovascular (CV) comorbidity in cancer. Objectives: The purpose of this study was to examine clinical characteristics and contemporary management of patients with AF and cancer with a specific focus on antithrombotic treatments. Methods: This was a prospective, multicenter, observational study of patients with a recent cancer diagnosis and electrocardiographically confirmed AF (the BLITZ-AF Cancer Registry). CHA2DS2VASc scores were calculated for study participants. Results: Overall, 1,514 individuals were enrolled from June 2019 to September 2021 (mean age 74 ± 9 years, 47.5% of participants >75 years of age; 63.5% males). CV diseases were common: 20.9% had heart failure, 18.1% had coronary artery disease, 38.5% had valvular heart disease, and 9.8% had peripheral artery disease. Previous thromboembolic and hemorrhagic events occurred in 13.9% and 10.4% of subjects, respectively. The most common cancer types were lung (14.9%), colorectal (14.1%), prostate (8.8%), and non-Hodgkin lymphoma (8.1%). In total, 41.5% of the patients had a CHA2DS2VASc score ≥4. Before admission or prior to cardiologist consultation, 16.6% of subjects were not taking any antithrombotic therapy and 22.7% were receiving antiplatelet agents and/or low-molecular-weight heparin. At discharge or after cardiologic assessment, these percentages dropped to 7.7% and 16.6%, respectively. This trend was paralleled by an increase in the use of direct-acting oral anticoagulant, while the proportion of vitamin K antagonist declined. Conclusions: This study demonstrates that there is underuse of appropriate antithrombotic therapy for AF in cancer patients highlighting the need to integrate early CV assessment in the management of these patients. (Non-interventional Study on Patients With Atrial Fibrillation and Cancer [BLITZ-AF Cancer]; NCT03909386).

[BLITZ-AF Cancer study: an international observational research project on patients with atrial fibrillation and cancer]. / Studio BLITZ-AF Cancer: un progetto di ricerca osservazionale internazionale sui pazienti con fibrillazione atriale e cancro.

BACKGROUND: Cancer is an important condition associated with the development of atrial fibrillation (AF). The objectives of the BLITZ-AF Cancer study were to collect real-life information on the clinical profile and use of antithrombotic drugs in patients with AF and cancer to improve clinical management, as well as the evaluation of the association between different antithrombotic treatments (or their absence) and the main clinical events. METHODS: European multinational, multicenter, prospective, non-interventional study conducted in patients with AF (electrocardiographically confirmed) and cancer occurring within 3 years. The CHA2DS2-VASc and the HAS-BLED scores were calculated in all enrolled patients. RESULTS: From June 2019 to July 2021, 1514 patients were enrolled, 36.5% women, from 112 cardiology departments in 6 European countries (Italy, Belgium, the Netherlands, Spain, Portugal and Ireland). Italy enrolled 971 patients in 77 centers. Average age of patients was 74 ± 9 years, of which 20.9% affected by heart failure, 18.1% by ischemic heart disease, 9.8% by peripheral arterial disease and 38.5% by valvular diseases; 41.5% of patients had a CHA2DS2-VASc score ≥4. The most represented cancer sites were lung (14.9%), colorectal tract (14.1%), prostate (8.8%), or non-Hodgkin's lymphoma (8.1%). Before enrollment, 16.6% of patients were not taking antithrombotic therapy, while 22.7% were on therapy with antiplatelet agents and/or low molecular weight heparin. After enrollment these percentages decreased to 7.7% and 16.6%, respectively and, at the same time, the percentage of patients on direct oral anticoagulant (DOAC) therapy increased from 48.4% to 68.4%, also to the detriment of those on vitamin K antagonist therapy. CONCLUSIONS: The BLITZ-AF Cancer study, which enrolled patients diagnosed with AF and cancer, highlights that the use of DOACs by cardiologists in this clinical context has increased, even though the guidelines on AF do not give accurate indications about oral anticoagulant therapy in patients with cancer.

Unmet needs and barriers in venous thromboembolism education and awareness among people living with cancer: a global survey.

BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored. RESULTS: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSION: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management.

Apixaban thromboprophylaxis in ambulatory patients with cancer and obesity: Insights from the AVERT trial.

BACKGROUND: The use of direct oral anticoagulants (DOACs) in obese patients is uncertain. It is unclear if body mass index (BMI) affects the safety and efficacy of DOACs for the primary prevention of venous thromboembolism (VTE) in high-risk ambulatory patients with cancer. We sought to determine the outcomes associated with the use of apixaban for the primary prevention of cancer-associated VTE according to BMI. METHODS: The randomized, double-blinded, placebo-controlled AVERT trial evaluated apixaban thromboprophylaxis in intermediate-to-high risk ambulatory cancer patients receiving chemotherapy. For this post-hoc analysis, the primary efficacy and safety outcomes were objectively confirmed VTE and clinically relevant bleeding (major and clinically relevant non-major bleeding), respectively. Obesity was defined as BMI ≥30 kg/m2. RESULTS: Among 574 patients randomized, 217 (37.8 %) patients had BMI ≥30 kg/m2. Obese patients were overall younger, more likely to be female, had higher creatinine clearance and hemoglobin, lower platelet count, and better ECOG performance status. Compared to placebo, apixaban thromboprophylaxis was associated with reduced VTE in both obese (hazard ratio [HR] 0.26; 95 % confidence interval [CI], 0.14-0.46; p < 0.0001) and non-obese (HR 0.54; 95%CI, 0.29-1.00; p = 0.049) patients. The HR for clinically relevant bleeding (apixaban vs. placebo) was numerically higher in obese (2.09; 95%CI, 0.96-4.51; p = 0.062) than non-obese subjects (1.23; 95%CI, 0.71-2.13; p = 0.46), but overall in line with the risks observed in the general trial population. CONCLUSIONS: In the AVERT trial enrolling ambulatory cancer patients receiving chemotherapy, we found no substantial differences in the efficacy or safety of apixaban thromboprophylaxis across obese and non-obese subjects.

Age- versus clinical pretest probability-adjusted D-dimer to rule out lower-extremity deep vein thrombosis in ambulatory patients with active cancer.

BACKGROUND: In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain. AIM: To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule. PATIENTS AND METHODS: Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism. RESULTS: Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate. CONCLUSIONS: In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting.

Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study.

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies. OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE). METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity. RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47). CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.

Awareness of venous thromboembolism among patients with cancer: Preliminary findings from a global initiative for World Thrombosis Day.

BACKGROUND: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty. METHODS: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media. RESULTS: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received. CONCLUSIONS: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden.

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis.

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.

Unanswered questions in cancer-associated thrombosis.

Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. Treatment of cancer-associated VTE comes with a heightened risk of anticoagulant-related bleeding that differs by choice of anticoagulant as well as by patient- and disease-specific risk factors. Available data from randomized controlled trials and observational studies in cancer-associated VTE suggest that direct oral anticoagulants are effective, continuing anticoagulation beyond six months is indicated in those with active cancer and that patients who develop 'breakthrough' thrombotic events can be effectively treated. We review the evidence that addresses these key clinical questions and offer pragmatic approaches in individualizing care. While significant investigative efforts over the past decade have made impactful advances, future research is needed to better define the factors that contribute to anticoagulant-related bleeding and VTE recurrence, in order to aid clinical decision-making that improves the care of patients with cancer-associated VTE.

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.

Antithrombotic treatment of retinal vein occlusion: a position statement from the Italian Society on Thrombosis and Haemostasis (SISET).

Retinal vein occlusion (RVO) represents a common cause of visual impairment and blindness. RVO may be associated with both local (e.g., hyperopia, glaucoma) and systemic (e.g., hypertension, diabetes, smoking, obesity, and dyslipidaemia) risk factors. The association with thrombophilia remains controversial. Data on the use of antithrombotic therapy for RVO are poor and inconsistent with most of the information being derived from observational studies. Here we provide a position statement from the Italian Society on Thrombosis and Haemostasis (SISET) to guide the clinical and therapeutic management of patients with RVO based on the available evidence and expert opinion.

Anticoagulant treatment for upper extremity deep vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: Data on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE). OBJECTIVES: The objective of this meta-analysis was to evaluate the efficacy and safety of anticoagulant therapy for UEDVT. PATIENTS/METHODS: A systematic search of MEDLINE and EMBASE was conducted for studies including patients with UEDVT. Primary outcomes were recurrent VTE and major bleeding. Secondary outcomes included clinically-relevant non-major bleeding and all-cause mortality. Summary estimates with 95% confidence intervals (CIs) were calculated by random-effect meta-analysis. RESULTS: A total of 1473 patients from 11 prospective and nine retrospective studies were included. Sixty percent of patients had an indwelling catheter and 56.1% had cancer. Anticoagulant treatment consisted of direct oral anticoagulants, low molecular weight heparin followed by vitamin K antagonists, and low molecular weight heparin alone in 45.1%, 35.0%, and 19.9% of patients, respectively. During a median follow-up of 13 months, recurrent VTE occurred in 3% of patients (95% CI: 2-4; 21/1334 patients), major bleeding in 3% (95% CI: 2%-5%; 29/1235 patients), clinically-relevant non-major bleeding in 4% (95% CI: 3-6; 40/1075 patients), and all-cause mortality in 9% (95% CI: 5-15; 108/1084 patients). Rates of these outcomes were not significantly different between patients with or without cancer, patients with or without an indwelling catheter, and among those receiving different anticoagulant treatments. CONCLUSIONS: In patients with UEDVT, anticoagulant treatment is associated with a low risk of recurrent VTE and a nonnegligible risk of major bleeding.

The prognostic value of respiratory symptoms and performance status in ambulatory cancer patients and unsuspected pulmonary embolism; analysis of an international, prospective, observational cohort study.

BACKGROUND: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR. OBJECTIVES: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort. METHODS: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule. RESULTS: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively). CONCLUSION: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort.

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban.

BACKGROUND: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients. OBJECTIVES: To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. PATIENTS/METHODS: In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type. RESULTS: Twenty-four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5). CONCLUSION: Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.

Risk Assessment Models for Thrombosis and Anticoagulant-Related Bleeding in Ambulatory Cancer Patients.

Cancer patients have a high risk of developing venous thromboembolism and arterial thrombosis, along with an increased risk of anticoagulant-related bleeding with primary and secondary prophylaxis of cancer-associated thrombosis. Decisions on initiation, dosing, and duration of anticoagulant therapy for prevention and treatment of cancer-associated thrombosis are challenging, as clinicians have to balance patients' individual risk of (recurrent) thrombosis against the risk of bleeding complications. For this purpose, several dedicated risk assessment models for venous thromboembolism in cancer patients have been suggested. However, most of these scores perform poorly and have received limited to no validation. For bleeding and arterial thrombosis, no risk scores have been developed specifically for cancer patients, and treatment decisions remain based on clinical gestalt and rough and unstructured estimation of the risks. The aims of this review are to summarize the characteristics and performance of risk assessment scores for (recurrent) venous thromboembolism and discuss available data on risk assessment for bleeding and arterial thrombosis in the cancer population. This summary can help clinicians in daily practice to make a balanced decision when considering the use of risk assessment models for cancer-associated venous thromboembolism. Future research attempts should aim at improving risk assessment for arterial thrombosis and anticoagulant-related bleeding in cancer patients.

Management of upper extremity deep vein thrombosis: an updated review of the literature.

Upper extremity deep vein thrombosis (UEDVT) represents about 5-10% of all cases of deep vein thrombosis (DVT) with a steadily increasing incidence mostly due to the high prevalence of cancer and frequent use of intravascular devices such as central venous catheters and pacemaker. In primary UEDVT, the venous outflow obstruction and subsequent thrombosis are related to congenital or acquired anatomical abnormalities, whereas secondary UEDVT is often associated with malignancy or indwelling lines. A considerable proportion of patients with UEDVT develops serious complications such as recurrent thrombosis, post-thrombotic syndrome, and pulmonary embolism, therefore timely diagnosis and adequate treatment are of crucial importance. Despite sharing many similarities with lower extremity DVT, UEDVT has distinctive features requiring specific diagnostic and therapeutic approaches. The present review discusses the latest evidence on the epidemiology, diagnosis, and treatment of UEDVT, and provides management indications which may help guide clinical decision making.

Treatment of venous thromboembolism in cancer patients: The dark side of the moon.

Venous thromboembolism (VTE) is a common complication in patients with cancer. The risk of emergent VTE is four- to seven-fold higher in cancer patients compared to non-cancer patients. Although the therapeutic armamentarium for cancer-associated VTE has been recently implemented, anticoagulant treatment remains challenging because of the increased risk of recurrent VTE and bleeding. Several international societies and expert panels released clinical practice guidelines on VTE treatment which are mostly focused on the general cancer population. Nevertheless, recommendations for the management of VTE in patients with peculiar clinical presentations are inconsistent and remain elusive due to the lack of pertinent evidence. The challenging clinical scenarios include, among others, patients with thrombocytopenia, renal impairment, gastrointestinal cancer, primary or metastatic brain cancer, distal thrombosis of the lower extremities, catheter-related VTE, splanchnic thrombosis, incidental VTE, extreme body weight, recurrent VTE during treatment, as well as the optimal duration of anticoagulant treatment in patients with active disease who have received 3 to 6 months of anticoagulation. Herein, we present a critical overview on VTE management in these challenging clinical settings, discuss potential approaches, and include some calls to action for future clinical research.