Cancer-associated splanchnic vein thrombosis: Clinical implications and management considerations.

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management.

Management and outcomes of superficial vein thrombosis: a single-center retrospective study.

Background: Guidelines suggest but cannot recommend the optimal management of superficial vein thrombosis (SVT). Objectives: To identify the prevalence of asymptomatic deep vein thrombosis (DVT) at the time of SVT diagnosis, and to report the treatment and 3-month complications of patients with only SVT more than 3 cm from deep vein junction (or unknown distance). Methods: We performed a single-center retrospective review of patients referred to the Ottawa Hospital thrombosis unit with ultrasound (US)-diagnosed SVT, and followed patients with only SVT for 3 months. Results: Three hundred sixteen patients with SVT were included. Of the 218 patients without DVT symptoms at presentation, 19 (8.7%; 95% CI, 5.7%-13.2%) were found to have asymptomatic concomitant DVT (11 proximal and 8 distal), and 45 (20.6%) had SVT within 3 cm of the saphenofemoral or saphenopopliteal junctions. Among the 192 patients diagnosed with SVT only, we observed 3-month thrombotic complications in 56 (29.2%; 95% CI, 23.2%-36.0%) patients, with a total of 69 events: 11 (5.7%) DVTs, 2 (1.0%) pulmonary embolisms, 37 (19.2%) SVT extensions, and 19 (9.8%) SVT recurrences. Eighty-two percent (9/11) of the 3-month DVT and pulmonary embolism events occurred in patients who initially received conservative management. Therapeutic treatment doses were most effective. Conclusion: At the time of SVT diagnosis, many patients had asymptomatic DVT and SVT near the deep venous system, supporting the systematic use of initial US in patients clinically diagnosed with SVT. The observed differences in 3-month complication rates, according to the treatment provided, highlight the need for large-scale randomized controlled trials to establish optimal management.

Anticoagulant therapy for splanchnic vein thrombosis: recent updates for patients with liver cirrhosis.

INTRODUCTION: Liver cirrhosis is accompanied by several hemostatic alterations, which contribute to the current theory of "rebalanced hemostasis." Splanchnic vein thrombosis (SVT) is a frequent complication of liver cirrhosis (17-26% of the cirrhotic patients), and liver cirrhosis is a common risk factor for SVT (24-28% of SVT cases). AREAS COVERED: This narrative review aims to describe the current state of the art on the anticoagulant treatment of cirrhotic SVT, with a particular focus on the possible role of the direct oral anticoagulants (DOACs) and recent guidelines on this topic. EXPERT OPINION: Early anticoagulant therapy is recommended in cirrhotic patients with acute SVT, to obtain vessel recanalization and decrease the rates of portal hypertension-related complications. Gastroesophageal varices do not represent a contraindication to anticoagulation, if adequate prophylaxis of variceal bleeding is established, and varices band ligation can be safely performed without the need to stop the anticoagulant treatment. The conventional treatment of cirrhotic SVT consisted of low molecular weight heparin, as initial treatment of choice, eventually followed by vitamin K antagonists, but the DOACs can be considered as a reasonable alternative in patients with compensated liver cirrhosis.

The risk of major bleeding in patients with factor V Leiden or prothrombin G20210A gene mutation while on extended anticoagulant treatment for venous thromboembolism.

BACKGROUND: Thrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants. OBJECTIVES: To assess whether thrombophilia is protective against bleeding. METHODS: This multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers). RESULTS: Of 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03). CONCLUSION: This study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.

Role of statins in the prevention of post-thrombotic syndrome after a deep vein thrombosis event: a systematic review and meta-analysis.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent long-term complication of deep vein thrombosis. Apart from anticoagulation, there are no medications, procedures, devices, or lifestyle changes that effectively prevent PTS. There is a growing interest in the potential protective effects of statins for the prevention of PTS. OBJECTIVE: To conduct a systematic review and meta-analysis on the role of statins to prevent PTS after a DVT event. METHODS: We searched the MEDLINE(R) ALL, Embase, Cochrane Central Register of Controlled Trials, and Scopus from inception to April 5, 2022. The main concepts searched were "statins" and "post thrombotic syndrome." There was no language restriction. The main outcome measure was the incidence rate ratio (IRR) for PTS associated with exposure to statins. RESULTS: Of 1971 screened records, 5 studies were included in the meta-analysis (2 retrospective cohorts and 3 randomized controlled trials [RCTs]). The pooled incidence of PTS was 34.8% per patient-year (95% CI, 9.5-127.4) in patients receiving a statin and 41.6% per patient-year (95% CI, 13.2-132) in controls. Exposure to statins was associated with a significantly decreased risk of PTS (IRR, 0.78; 95% CI, 0.63-0.96, I2 = 0%). Meta-analysis of the 2 retrospective cohorts found a significant reduction in the risk of developing PTS (IRR, 0.68; 95% CI, 0.51-0.91), whereas meta-analysis of RCTs showed no reduction in PTS occurrence (IRR, 0.92; 95% CI, 0.68-1.25). CONCLUSIONS: Although this systematic review suggests that statins may reduce PTS incidence by 22% after deep vein thrombosis, meta-analysis of RCTs showed no risk reduction. Confirmation of the efficacy of statins on the prevention of PTS should be assessed in larger RCTs.

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Association between body mass index, waist circumference, and relative fat mass with the risk of first unprovoked venous thromboembolism.

BACKGROUND AND AIMS: Obesity defined by body mass index (BMI) is independently associated with venous thromboembolism (VTE). Abdominal obesity, defined by waist circumference, is a predictor of cardiovascular events. Recently, relative fat mass (RFM) was proposed as a marker of cardiovascular risk. We assessed the role of three different measures of obesity to predict unprovoked VTE in a longitudinal study. METHODS AND RESULTS: Moli-sani is a prospective cohort study carried out in the general population of the Molise region, Italy. A total of 23,538 individuals (48% men, age 55.4 years) enrolled between 2005 and 2010 were eligible. Patients on anticoagulant treatment were excluded. BMI ≥30 kg/m2 defined obesity, waist circumference >102 cm for men or 88 cm for women defined abdominal obesity, tertiles of RFM were compared. The long-term incidence of first unprovoked VTE during follow-up was assessed. Overall, 29.6% individuals were obese and 44.2% had abdominal obesity. A total of 66 first unprovoked VTE events were diagnosed during a median follow-up of 8.2 years. After multivariable Cox regression analysis, the risk of unprovoked VTE was significantly higher in obese participants (HR 1.89, 95% CI 1.16-3.07) than in participants with BMI <30; in subjects with abdominal obesity than with normal waist circumference (HR 2.19, 1.26-3.81); and in subjects with third vs first RFM tertile index (HR 2.46, 1.15-5.28). The areas under the curves for the models including the three obesity indexes were comparable. CONCLUSIONS: Three indexes of obesity based on BMI, waist circumference or RFM similarly predict first occurrence of unprovoked VTE.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: A systematic review and meta-analysis of the literature.

BACKGROUND: Postoperative venous thromboembolism (VTE) is a significant source of morbidity and mortality in cancer patients undergoing major abdominopelvic surgery. Many guidelines recommend the use of extended duration postoperative low molecular weight heparin (LMWH) thromboprophylaxis, although the evidence for its overall safety and efficacy is unclear. AIMS: We sought to assess the 30-day postoperative rates of VTE and bleeding complications following major abdominopelvic cancer surgery and to explore the potential risks and benefits of extended duration thromboprophylaxis with LMWH in such setting. METHODS: A systematic search of the literature was conducted. Observational studies and RCTs of adult patients that underwent abdominopelvic cancer surgery were included. Pooled proportions for the outcome measures and pooled relative risks for the extended duration thromboprophylaxis analyses were generated. RESULTS: A total of 68 studies (1,631,118 patients) were included in the analysis. The 30-day postoperative rate of VTE was 1.7% (95%CI: 1.5 to 1.9, I2 = 98%). The postoperative rate of clinically-relevant bleeding complications was 3.5% (95%CI: 1.6 to 6.1, I2 = 99%). Extended duration thromboprophylaxis was associated with a significant reduction in the incidence of clinical VTE (1.0% vs 2.1%; Risk ratio (RR) 0.48, 95%CI: 0.31 to 0.74; I2 = 0), without a significant increase in clinically-relevant bleeding (4.0% vs. 4.9%; RR 1.0, 95%CI: 0.66 to 1.5, I2 = 0). CONCLUSIONS: The overall risk of symptomatic VTE within 30 days of surgery was relatively low. Extended LMWH thromboprophylaxis following major abdominopelvic cancer surgery was associated with a reduced incidence of clinical VTE without an increase in clinically-relevant bleeding.

Outcomes among patients with cancer and incidental or symptomatic venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Patients with cancer have an increased risk of venous thromboembolism (VTE) and it is commonly detected incidentally. The outcomes and optimal management for patients with cancer and incidental VTE remain debated. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate the outcomes in patients with cancer and incidentally detected VTE compared to those with symptomatic events. PATIENTS/METHODS: We searched the electronic databases and included randomized controlled trials (RCTs) and observational studies reporting recurrent VTE, major bleeding events, and mortality in patients with cancer and incidental VTE compared to symptomatic VTE. RESULTS: We included 23 studies for the systematic review: 3 RCTs and 20 observational studies. The meta-analysis of the 3 RCTs showed a significantly lower rate of VTE recurrence at 6 months in patients with incidental VTE compared to those with symptomatic VTE (relative risk [RR] 0.62, 95% confidence interval [CI] 0.44-0.87). The risk of major bleeding events at 6 months was numerically higher with incidental VTE compared to symptomatic VTE (RR 1.47, 95% CI 0.99-2.20). There was no difference in overall mortality. CONCLUSIONS: Among patients with cancer, incidental VTE was associated with a lower rate of VTE recurrence compared to symptomatic VTE, with a trend in increased major bleeding events. The risk-benefit ratio of anticoagulation may differ between incidental and symptomatic events and should be considered in patient management.

Cancer-Associated Splanchnic Vein Thrombosis.

Splanchnic vein thrombosis (SVT), which includes portal, mesenteric, and splenic vein thrombosis and the Budd-Chiari syndrome, is an infrequent manifestation of venous thromboembolism (VTE). Like typical site VTE, SVT is also frequently associated with cancer, particularly intra-abdominal solid malignancies and myeloproliferative neoplasms (MPNs). The clinical presentation of SVT is nonspecific. Symptoms may be related to the underlying malignancy, and thrombosis is incidentally diagnosed by imaging studies for cancer staging or follow-up in a substantial proportion of cases. The occurrence of SVT predicts worse prognosis in patients with liver or pancreatic cancer and, not uncommonly, SVT may precede the diagnosis of cancer. Therefore, the occurrence of an apparently unprovoked SVT should prompt careful patient evaluation for the presence of an underlying malignancy or MPN. Cancer patients carry a high risk of VTE extension and recurrence and long-term anticoagulant treatment is suggested in the absence of high risk of bleeding. Either LMWH or direct oral anticoagulants (DOACs) are suggested for the treatment of patients with cancer-related SVT, although limited experience is available on the use of DOACs in these settings. Vitamin K antagonists (VKAs) are suggested for the short and long-term treatment of SVT associated with MPN. This review outlines the epidemiological aspects, pathogenesis, risk factors, and diagnosis of cancer-associated SVT, and addresses questions regarding the management of this challenging condition.

Efficacy and safety of apixaban for primary prevention in gastrointestinal cancers: A post-hoc analysis of the AVERT trial.

BACKGROUND: Recent trials have demonstrated that thromboprophylaxis using direct oral anticoagulants is effective but associated with a higher rate of major bleeding in intermediate-to-high risk (Khorana score ≥ 2) patients with cancer initiating systemic chemotherapy. Patients with gastrointestinal cancer may be at higher risk of major bleeding complications. We sought to assess the efficacy and safety of using thromboprophylaxis with apixaban in this patient population. METHODS: This is a post-hoc analysis of the AVERT trial, which was a randomized, placebo-controlled, double-blind clinical trial. The primary efficacy outcome was objectively documented venous thromboembolism within 180 days of randomization. The primary safety outcome was a major bleeding episode. Time-to-event analyses were performed in patients with gastrointestinal cancers (upper gastrointestinal, pancreatic/hepatobiliary and colorectal cancers). RESULTS: A total of 130 patients from the original AVERT trial were included, with 65 patients allocated to each of the apixaban and placebo groups. VTE occurred in 3 (4.6%) patients in the apixaban group and 13 (20%) patients in the placebo group (HR: 0.27; 95% CI: 0.13-0.54; p = 0.0002). Major bleeding occurred in 2 (3.1%) patients in the apixaban group and 1 (1.5%) patient in the placebo group (HR 2.39, 95% CI 0.29-19.78, p = 0.42). None of the major bleeding events occurred in patients with upper gastrointestinal or colorectal cancers. CONCLUSION: Primary thromboprophylaxis with apixaban therapy seems to be safe and effective in patients with gastrointestinal cancers. Major bleeding complications are uncommon in our cohort. (Funded by the CIHR and Bristol-Myers Squibb-Pfizer Alliance; NCT02048865).

Treatment of portal vein thrombosis: an updated narrative review.

Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). Anticoagulant therapy in patients with acute symptomatic PVT should be started early after diagnosis, if no active bleeding, to obtain greater vessel recanalization and reduce the occurrence of portal-hypertension related complications. Gastroesophageal varices do not represent a contraindication to anticoagulant treatment, as long as adequate measures have been undertaken for the prophylaxis of gastroesophageal bleeding. Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarize recent guidelines on this topic.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Clinical history of cancer-associated splanchnic vein thrombosis.

BACKGROUND: Cancer represents a risk factor for splanchnic vein thrombosis (SVT) and usual site venous thromboembolism (VTE). OBJECTIVES: To compare characteristics and outcomes of patients with cancer-associated SVT and usual site VTE. PATIENTS/METHODS: Patients with solid cancer and SVT were enrolled in an international, prospective registry between May 2008 and January 2012. The comparison cohort included (1:1 ratio) patients with solid cancer and usual site VTE treated at two thrombosis centers who had a minimum of 12 months follow-up at December 2019 or experienced one of the outcomes within 12 months follow-up. Recurrent VTE, major bleeding, and all-cause mortality were evaluated at 12-month follow-up. RESULTS: A total of 264 patients (132 in each cohort) were enrolled. Patients with SVT were less likely to have metastatic disease (36.1% vs 72.5%) or receive cancer therapy at thrombosis diagnosis (29.6% vs 64.9%). The most frequent cancer types were hepatobiliary and pancreatic in the SVT cohort and gastrointestinal in the usual site VTE cohort. Fewer patients with SVT received anticoagulation (68.9% vs 99.2%), and treatment duration was shorter (6.0 vs 11.0 months). The cumulative incidence of major bleeding (2.3% vs 4.7%) was nonsignificantly lower in the SVT cohort, whereas recurrent thrombosis (4.7% vs 5.5%) and all-cause mortality (41.7% vs 39.4%) were comparable between the two cohorts. CONCLUSIONS: The risk of recurrent thrombosis and bleeding appears to be similar in cancer patients with SVT and cancer patients with usual site VTE, despite some differences in baseline characteristics and anticoagulant treatment. Further prospective studies are warranted to confirm these findings.

Coagulation parameters and venous thromboembolism in patients with and without COVID-19 admitted to the Emergency Department for acute respiratory insufficiency.

BACKGROUND: In the recent outbreak of COVID-19 pandemic, increased D-dimer levels and high rates of venous thromboembolic events were reported. We aimed to compare coagulation parameters on admission between COVID-19 patients and non-COVID-19 patients with acute respiratory insufficiency and to describe VTE diagnosed at entry. METHODS: In this single-centre, observational retrospective study consecutive patients admitted for fever and acute respiratory failure were included. Patients underwent laboratory tests, arterial blood gas, chest X-ray, point of care ultrasound (POCUS), limited compression ultrasonography of the lower limbs (L-CUS), chest CT-scan if necessary, and swab test for COVID-19. RESULTS: Of 324 patients, 50% had COVID-19. COVID19 patients had significantly lower mean white blood cells, neutrophils, platelet count, and pCT values, and significantly higher CRP, LDH, and ferritin levels than non-COVID19 patients. D-dimer was increased in 86.5% COVID19 patients and in 84.9% non-COVID19 patients; mean values were similar (2185 ng/mL and 2814 ng/mL, respectively, p = n.s.). After multivariate analysis, results were unchanged (Odds Ratio 1.00 95%CI: 0.99-1.00, p = 0.21). PT and aPTT values were also similar between the two groups, fibrinogen levels were higher in COVID19 than in non-COVID19 patients (684 and 496 mg/dL, respectively, p < 0.0001). Five patients had asymptomatic proximal deep vein thrombosis detected by L-CUS (3 COVID19) and 2 patients had symptomatic pulmonary embolism (both non-COVID19). CONCLUSIONS: D-dimer levels were similarly increased in patients with and without SARS-CoV 2 related disease. There were few cases of asymptomatic deep vein thrombosis or symptomatic pulmonary embolism at first day of admission, similarly distributed between COVID19 patients and non-COVID19 patients.

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

BACKGROUND AND AIMS: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. METHODS AND RESULTS: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. CONCLUSIONS: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.