Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis.

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT. RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Sepsis Outcome after Major Abdominal Surgery Does Not Seem to Be Improved by the Use of Pentameric Immunoglobulin IgM: A Single-Center Retrospective Analysis.

BACKGROUND: Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery. MATERIALS/METHODS: We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed. RESULTS: Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations. CONCLUSIONS: Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery.

Corrigendum: Diagnostic and therapeutic management of the thoracic outlet syndrome. Review of the literature and report of an Italian experience.

[This corrects the article DOI: 10.3389/fcvm.2022.802183.].

Ischaemic Stroke Occurring in a Patient Treated with Monoclonal Antibodies for COVID-19.

Since the COVID-19 outbreak began, an association between COVID-19 and thrombotic diseases has been underlined. Although this association is more frequent with venous thromboembolism, ischaemic stroke has also been reported as a thrombotic complication in several cohorts of affected patients. Furthermore, the association between ischaemic stroke and COVID-19 has been considered a risk factor for early mortality. On the other hand, after the successful vaccination campaign, the incidence and the virulence of SARS-CoV-2 decreased, though it has been observed that COVID-19 may induce a severe infection in specific cohorts of frail subjects. For this reason, different drugs have been introduced of an antiviral action in order to improve the disease outcome of frail patients. In this field, with the arrival of a neutralizing monoclonal antibody against SARS-CoV-2, in particular, sotrovimab, a further chance to treat high-risk patients with mild-to-moderate COVID-19 arrived, achieving a concrete reduction in the risk of disease progression. We here report our clinical experience of an ischaemic stroke occurring a few minutes after the administration of sotrovimab for the treatment of moderate COVID-19 in a frail patient with chronic lymphocytic leukaemia. Other causes of ischaemic stroke were ruled out, and in order to evaluate the probability of a rare side effect, the Naranjo probability scale has also been utilized. In conclusion, among several side effects that have been described during the treatment of COVID-19 with sotrovimab, ischaemic stroke was not reported. Therefore, we here report a rare case of ischaemic stroke with early clinical manifestation after the administration of sotrovimab for the treatment of moderate COVID-19 in an immunocompromised patient for the first time.

Safety and Efficacy of Rivaroxaban as Extended-Phase Anticoagulation in Patients with Cancer and Venous Thromboembolism: A Preliminary Data Analysis from the Mac Project.

Extended-phase anticoagulation with direct oral Xa inhibitors (OAXI) is suggested in patients with cancer-associated venous thromboembolism (CAT). We report on patients enrolled in the MAC (Monitoring AntiCoagulants) Project, given rivaroxaban as extended-phase anticoagulation after CAT. The primary efficacy outcome was the incidence of symptomatic recurrent VTE; the primary safety outcomes were incidence of major and non-major clinically relevant bleeding, adverse events, and all-cause mortality. The mean patients' follow-up was 19 months (SD 16); 64/604 (11%) had CAT. Recurrent VTE occurred in 9.3% and in 8.1% of patients with and without CAT (OR 1.2, 95% CI 0.5 to 2.9; p = 0.6). Major bleeding occurred in 4.7% and in 2.6%, respectively (OR = 1.8, 95% CI 0.5 to 6.6, p = 0.4), and non-major clinically-relevant bleeding in 4.7% and in 4.1% (OR = 1.2, 95% CI 0.3 to 3.9, p = 0.7). The relative figures for fatal haemorrhage and all-cause death were 1.6% versus 0%, and 1.6% versus 0.4%. Rivaroxaban appears to be effective and safe as extended-phase anticoagulation in patients with CAT. The mean treatment period was 3-times the standard 6-month course.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy.

Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy­1485 (58.6%); delayed start­808 (32.5%); low doses­143 (5.7%); both conditions­54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97−170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25−6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

New-Onset Atrial Fibrillation and Early Mortality Rate in COVID-19 Patients: Association with IL-6 Serum Levels and Respiratory Distress.

Background and objectives: COVID-19 is associated with an aberrant inflammatory response that may trigger new-onset cardiac arrhythmias. The aim of this study was to assess the mortality risk in hospitalized COVID-19 patients according to IL-6 serum levels and new-onset atrial fibrillation (AF) according to PaO2/FiO2 stratification. Materials and Methods: 175 COVID-19 patients (25 new-onset AF, 22 other types of AF and 128 no-AF) were included in this single-center, retrospective study; clinical and demographic data, vital signs, electrocardiograms and laboratory results were collected and analyzed. The primary outcome of the study was to evaluate the mortality rate in new-onset AF patients according to IL-6 serum levels and PaO2/FiO2 stratification. Results: The incidence of new-onset AF in the study population was 14.2%. Compared to the no-AF group, new-onset AF patients were older with a positive history of chronic kidney disease and heart failure, had higher IL-6, creatinine and urea serum levels whereas their platelet count was reduced. After PaO2/FiO2 stratification, 5-days mortality rate was higher in new-onset AF patients compared to patients with other types of AF and no-AF patients, and mortality risk increases 5.3 fold compared to no-AF (p = 0.0014) and 4.8 fold compared to other forms of AF (p = 0.03). Conclusions: New-onset AF is common in COVID-19 patients and is associated with increased IL-6 serum levels and early mortality. Further studies are needed to support the use of IL-6 as an early molecular target for COVID-19 patients to reduce their high rate of mortality.

Diagnostic and Therapeutic Management of the Thoracic Outlet Syndrome. Review of the Literature and Report of an Italian Experience.

The Thoracic Outlet Syndrome is a clinical potentially disabling condition characterized by a group of upper extremity signs and symptoms due to the compression of the neurovascular bundle passing through the thoracic outlet region. Because of the non-specific nature of signs and symptoms, to the lack of a consensus for the objective diagnosis, and to the wide range of etiologies, the actual figure is still a matter of debate among experts. We aimed to summarize the current evidence about the pathophysiology, the diagnosis and the treatment of the thoracic outlet syndrome, and to report a retrospective analysis on 324 patients followed for 5 years at the Padua University Hospital and at the Naples Fatebenefratelli Hospital in Italy, to verify the effectiveness of a specific rehabilitation program for the syndrome and to evaluate if physical therapy could relieve symptoms in these patients.

Waldenstrom's Macroglobulinemia and Ascites: A Case Report.

Background: Waldenstrom's disease is characterized by the presence of pathological changes in the B lymphocytes that are in the last stages of maturation. One characteristic of WM is the production of an abnormal high amount of IgM and hyper viscosity syndrome. The MW gets worse, symptoms such as fatigue, weight loss, night sweats, fever, recurrent infections and swollen lymph nodes develop in patients who have a known history of MGUS. In this clinical case, our patient without history of MGUS, presents for the first time for medical observation only for ascites and the presence of an interportocaval lymph node package. An atypical presentation of the disease that makes us reflect on the difficulty of making a diagnosis in the elderly patient and on pathogenetic hypotheses of ascites not yet explored. Case Presentation: Seventy-three-year-old patient, hospitalized for the onset of ascites with sloping edema, diffuse left pulmonary opacification. At the ultrasound check, cava and portal vessels patent and of regular caliber, however with inversion of flow in correspondence with the right branch and of the door to the hilum, with a subdiaphragmatic retrocaval focus with a maximum diameter of about 3 cm, which cannot be better viewed. CT scan of the abdomen with confirmation of the presence of an interportocaval lymph node package. After evidence of the electrophoretic protein picture of a double component, probably monoclonal with positive urinary immunofixation for free K chains. IgM dosage equal to 2190 mg. Serum immunofixation practice that confirms the diagnosis of type B lymphoproliferative syndrome as per Waldenstrom's disease, confirmed by bone marrow aspiration with morphological and flow cytometric study. Immediately begin chemotherapy with Bendamustine 120 mg. After 4 weeks of therapy with the reduction of IgM values, the patient no longer presented ascites. Conclusion: This case has an unusual presentation of this disease and we could shed a new light on the possible pathogenesis of portal hypertension in Waldenstrom'disease.

Prognostic Impact of Active Cigarette Smoking on Mortality in Patients with Acute Venous Thromboembolic Events, Findings from Real World Data.

Background and Objectives: The influence of smoking habits on mortality, VTE recurrence, and major bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. Materials and Methods: We used data from the RIETE (Registro Enfermedad TromboEmbólica) registry to compare mortality, VTE recurrence, and major bleeding risk in smoking versus non-smoking patients with acute VTE. Results: 50,881 patients (43,426 non-smoking and 7455 smoking patients) were included. After a median follow-up of 8.8 months, 7110 patients died (fatal PE 292 and fatal bleeding 281), 3243 presented VTE recurrence, and 1579 had major bleeding. At multivariate analysis, smoking behavior was associated with a higher hazard of death, (HR: 1.28; 95% CI: 1.19-1.40). The risk of VTE recurrence was marginally increased in smoking patients compared to non-smoking patients (1.14; 95% CI: 1.02-1.27). Major bleeding did not differ in smoking and non-smoking patients (1.15; 95% CI: 0.96-1.38). The presence of cancer did not appear to influence the association between smoking habits and death (HR: 1.34; 95% CI: 1.22-1.47 in cancer patients and HR: 1.23; 95% CI: 1.04, 1.45 in non-cancer patients, respectively) Conclusions: the risk of death after an acute episode of VTE appeared to be higher in smoking than in non-smoking patients and this risk is higher between patients presenting PE at the onset of symptoms.

Machine Learning to Calculate Heparin Dose in COVID-19 Patients with Active Cancer.

To realize a machine learning (ML) model to estimate the dose of low molecular weight heparin to be administered, preventing thromboembolism events in COVID-19 patients with active cancer. Methods: We used a dataset comprising 131 patients with active cancer and COVID-19. We considered five ML models: logistic regression, decision tree, random forest, support vector machine and Gaussian naive Bayes. We decided to implement the logistic regression model for our study. A model with 19 variables was analyzed. Data were randomly split into training (70%) and testing (30%) sets. Model performance was assessed by confusion matrix metrics on the testing data for each model as positive predictive value, sensitivity and F1-score. Results: We showed that the five selected models outperformed classical statistical methods of predictive validity and logistic regression was the most effective, being able to classify with an accuracy of 81%. The most relevant result was finding a patient-proof where python function was able to obtain the exact dose of low weight molecular heparin to be administered and thereby to prevent the occurrence of VTE. Conclusions: The world of machine learning and artificial intelligence is constantly developing. The identification of a specific LMWH dose for preventing VTE in very high-risk populations, such as the COVID-19 and active cancer population, might improve with the use of new training ML-based algorithms. Larger studies are needed to confirm our exploratory results.

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients.

INTRODUCTION: No data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. MATERIALS AND METHODS: Data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett's formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. RESULTS: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty patients (23%) showed extreme QTc interval prolongation; no clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. CONCLUSIONS: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

Idiopathic Hypereosinophilia and Venous Thromboembolism: Is There a Pathophysiological or Clinical Link? Description of an Intriguing Clinical Case.

Thrombosis events usually occur after prolonged bedrest, pregnancy, hormonal therapy, recent surgery and in the presence of inherited or acquired thrombophilia. However, several other diseases are often associated with thrombosis although their frequency is not easily estimated. Eosinophilia is one of these conditions. From a clinical viewpoint it is very difficult to understand which conditions might lead to a thrombotic event because the underlying pathophysiological mechanisms are different. Here, we report a case of idiopathic hypereosinophilia associated to venous thromboembolism without any other associated prothrombotic condition.

Acquired Factor XIII Deficiency Inducing Recurrent and Fatal Bleeding, Description of a Case.

Factor XIII deficiency may be inherited or acquired. Inherited deficiency is associated with signs and symptoms of minor bleeding from a young age, and possible major bleeding complications, in particular during pregnancy. On the other hand, acquired factor XIII deficiency is usually associated with severe symptoms of major bleeding, in particular during surgery. In this paper, we report an interesting case of recurrent major bleeding with subsequent fatal bleeding in an adult man diagnosed with acquired factor XIII deficiency.

Morbid Obesity and Mortality in Patients With VTE: Findings From Real-Life Clinical Practice.

BACKGROUND: The influence of morbid obesity on mortality in patients receiving anticoagulant therapy for VTE has not been consistently evaluated. METHODS: Data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry were used to compare the mortality risk during anticoagulation in patients with VTE and morbid obesity (BMI ≥ 40 kg/m2) vs those with normal weight (BMI, 18.5-24.9 kg/m2). Patients with or without active cancer were analyzed separately. RESULTS: By September 2018, there were 1,642 patients with VTE and morbid obesity and 14,848 with normal weight in RIETE. Of these, 245 (5.5%) and 1,397 (11.6%), respectively, had cancer. Median duration of anticoagulant therapy was longer in the morbidly obese patients, with cancer (185 vs 114 days) or without cancer (203 vs 177 days). Among cancer patients, 44 (18.0%) morbidly obese and 1,377 (32.8%) patients with normal weight died during anticoagulation. Among those without cancer, 44 (3.1%) morbidly obese died and 601 (5.6%) with normal weight died. On bivariate analysis, morbid obesity was associated with a lower mortality rate, both in patients with cancer (hazard ratio, 0.34; 95% CI, 0.25-0.45) and in those without cancer (hazard ratio, 0.43; 95% CI, 0.32-0.58). Multivariable analysis confirmed a lower hazard of death in morbidly obese patients with cancer (hazard ratio, 0.68; 95% CI, 0.50-0.94) and without cancer (hazard ratio, 0.67; 95% CI, 0.49-0.96). The risk for VTE recurrences or major bleeding did not differ in patients with or without morbid obesity. CONCLUSIONS: In patients with VTE, the risk for death during anticoagulation was about one-third lower in morbidly obese patients than in those with normal weight, independently of the presence of cancer.

Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis.

INTRODUCTION: Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. METHODS: We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. RESULTS: In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71-5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47-2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14-8.17) and anaemia (HR: 4.11; 95%CI: 1.45-11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68-10.1) were associated with at increased risk for major bleeding. CONCLUSIONS: The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy.

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism.

BACKGROUND: Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. OBJECTIVES: To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non-fragile patients with VTE. METHODS: Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. RESULTS: From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37-0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10-1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16-2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05-12.4), all-cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75-2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10-2.85) than the non-fragile. CONCLUSIONS: In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non-fragile.