Development Of Venous Thromboembolic Events Research Articles

Is it safe to discontinue anticoagulant after surgical treatment of varicose vein disease, which caused pulmonary embolism?

Superficial vein thrombosis, which is mostly caused by lower extremity varicose vein disease, can be complicated by pulmonary embolism. At the same time, the optimal duration of anticoagulant therapy for pulmonary embolism originated from varicose vein thrombosis is still under debate. On the one hand, the presence of varicose veins is considered a small risk factor for the development of venous thromboembolic events, which persistence determines an increased risk of relapse and requires prolonged anticoagulant therapy. On the other hand, elimination of varicose veins is associated with reduced risk of subsequent venous thromboembolic events. The article describes a clinical case of recurrent pulmonary embolism after surgical treatment of varicose vein disease, which caused primary pulmonary embolism. A 45-year-old patient suffering from left lower extremity varicose vein disease for 5 years was admitted to the intensive care unit with suspected pulmonary embolism. The further examination revealed signs of thrombotic occlusion of the segmental and subsegmental branches of the pulmonary arteries bilaterally and the middle lobe branch of the right pulmonary artery, as well as signs of the right-sided heart overload. In this case, pulmonary embolism was found to originate from thrombosis of the trunk of the great saphenous vein ofthe left lower extremity with a proximal border at the level of the lower leg. No signs of deep vein involvement were detected. The parenteral anticoagulant therapy initiated in the hospital was followed by switching to therapeutic doses of rivaroxaban. The signs of recanalization of involved veins were identified after 6 months of treatment, and it was decided to perform endovenous laser coagulation of the trunk of the great saphenous vein combined with mini-phlebectomy of varicose tributaries on continuous oral anticoagulant therapy. The rivaroxaban therapy was completed a month after intervention. However, 7 days later the patient was diagnosed with repeated symptomatic pulmonary embolism, which originated from thrombosis of the left popliteal vein. It was recommended to resume anticoagulant therapy of indefinite duration. The article discusses the issues of optimal duration of treatment for pulmonary embolism originated from thrombosis of superficial varicose veins, as well as the possible timing of completion of anticoagulant therapy after the intervention.

The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

328 Incidence and Number of Missed Chemical Venous Thromboembolic Event Prophylactic Doses Predict the Development of Venous Thromboembolic Events in Traumatic Brain Injury Patients

INTRODUCTION: Venous thromboembolic events (VTE) are a major concern in trauma and intensive care, with traumatic brain injury (TBI) patients at an elevated risk. Chemical VTE prophylaxis is used to prevent VTE development. Concerning TBI patients, achieving a fine balance between the risk of worsening hemorrhage and clot development is important. To date, there has been no correlation between the number of missed doses and VTE development in this population. METHODS: Data were retrospectively collected among 818 TBI patients admitted to a level I trauma center between 2015-2020. RESULTS: Overall VTE incidence was 9% (7.6% DVT; 3.2% PE; 1.7% both). Median time to DVT and PE was 7 (IQR: 4-11) and 5 days (IQR: 3-12), respectively. VTE occurred in 37.8% of patients who missed prophylactic doses and 28.4% who did not (p = 0.089). In patients who experienced a VTE, compared to non-VTE patients, missed chemical prophylaxis dosing was primarily due to a pending invasive procedure (44.8% vs. 25.2%, p = 0.02) and the presence of additional bleeding (13.8% vs. 2.8%, p = 0.005). Non-VTE patients missed prophylactic dosing primarily from patient or family refusal (42.1% vs. 3.4%, p < 0.001). VTE incidence was higher in patients receiving invasive neurosurgery (45.9% vs. 30.5%, p = 0.007). Univariate analysis demonstrated 4-6 total missed doses as predicting the highest VTE risk (OR 4.08, 95% CI: 1.53-10.86, p = 0.005). No VTE were seen in >7 missed doses, presumably due to an overall high mortality rate of 13.5%. CONCLUSIONS: This study is novel in showing the incidence and number of missed chemical VTE prophylaxis to predict an increased VTE risk in TBI patients. Our study suggests a threshold of 4 missed doses to be particularly important in this critical patient population.

Cell Product Differences on Incidence of Venous Thromboembolism in Patients Treated with CAR T-Cells for Aggressive B-Cell Lymphomas

Introduction Chimeric antigen receptor T (CAR T)-cell therapy has substantial activity in relapsed lymphoid malignancies. However, it is associated with important complications, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolic events (VTEs) following CAR T-cells have been reported with variable incidence. Risk factors for the development of VTEs following CAR T-cell therapy are largely unknown, including whether the CAR T-cell construct is associated with increased VTEs. Methods We retrospectively evaluated patients treated at our institution who received CAR T-cell therapy for non-Hodgkin lymphoma between May 2018 and January 2022. Baseline characteristics and outcomes were collected. VTEs included deep venous thrombosis and pulmonary embolism. The cumulative incidence (CI) of VTE was calculated with death as competing risk and comparisons between groups were done with Gray test. Univariate comparisons of baseline parameters were performed with Fisher's exact test evaluating the following covariates: age (older or younger than 70 years), LDH and C-reactive protein levels, ECOG performance status, revised IPI, BMI, personal history of VTE, and stage. Due to the low number of VTEs, we did not attempt multivariate modeling based on baseline characteristics. All analyses were performed using R. This study was approved by our Institutional Review Board. Results We identified 95 patients treated with CAR T-cells between May 2018 and January 2022. The majority had diffuse large B-cell lymphoma (DLBCL) (88, 93%). Baseline characteristics are listed in Table 1. Prior history of VTE occurred in 16 patients and 27 received at least one dose of therapeutic or prophylactic anticoagulation post-CAR T infusion prior to developing VTE. Most patients had central venous access during their hospitalization for CAR T cell therapy (n = 91). A total of 56 patients received axicabtagene ciloleucel (58.9%), 30 patients received tisagenlecleucel (31.6%), 5 patients received brexucabtagene autoleucel (5.3%), and 4 received lisocabtagene maraleucel (4.2%). Post-CAR T VTE occurred in 13 patients (14%); median time to VTE (IQR) was 15 days (7-48), with a 100-day cumulative incidence of 12%. All VTEs were DVTs and the majority were PICC line-associated (10, 77%). The incidence of VTE was higher for patients treated with axicabtagene ciloleucel or brexucabtagene autoleucel in contrast to 41BB-containing constructs (16% vs. 3%, p = 0.03) (Figure 1). Among baseline characteristics, a prior history of VTE was associated with increased risk of subsequent VTE (39% vs. 13% without prior VTE, p = 0.04). The 100-day CI of VTE for patients with and without CRS were 15% and 4% (p = 0.09), while the 100-day CI of patients with and without ICANS were 18% and 7% (p = 0.09). Subgroup analysis of patients treated with CD3ζ/CD28 signaling showed that 100-day VTE CI was higher among patients with a prior history of VTE (33% vs. 12%, p = 0.03) and those with BMI of ≥ 30 (38% vs. 11%, p = 0.03). We did not observe an increased incidence of VTE in patients with baseline ECOG performance status ≥ 2, stage III/IV disease, elevated baseline lactate dehydrogenase or C-reactive protein. After a median follow up of 24 months (IQR 13-36), the median progression free survival (PFS) was 7 months (95% CI = 4-12) while the median overall survival (OS) was 14 months (95% CI = 11-19), there were no statistically significant differences in PFS or OS among patients with and without VTE. Conclusions VTEs are an emerging toxicity associated with CAR T cell therapy. We show that increased VTE incidence at 100 days is associated with the use of CD3ζ/CD28 CAR T-cells. This difference may correlate with differing degrees of systemic inflammatory response, as previous reports have detailed higher incidence of high-grade CRS with axicabtagene ciloleucel vs. tisagenlecleucel, and other construct-specific factors may further increase VTE risk in patients with established VTE risk factors (e.g. history of VTE and obesity). We also observed that a large proportion of post CAR T VTEs corresponded to line-associated DVTs. Taken together, these findings may help identify patients at increased risk of VTE after CAR T-cell therapy and potentially guide decisions on surveillance, choice of central access, or prophylactic anticoagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The problem of prevalence, thromboprophylaxis and diagnostic strategies of thromboembolism in patients with COVID-19

Annotation. Coronavirus infection is associated with a large number of complications, among which thromboembolisms of various localization are extremely serious. This article presents an overview of current literature data on the prevalence, need for thromboprophylaxis and strategic diagnostic goals in patients who have experienced thromboembolism of various vessels against the background of COVID-19. From the PubMed, ScienceDirect, UpToDate, Web of science, Scopus databases, 30 sources were selected and reviewed that met the query conditions: the most recent publications (over the last 5 years) or the latest publications on this issue (regardless of the age). Thromboembolic complications arising from COVID-19 correlate with increased disease severity and worsening of treatment outcomes. Patients with COVID-19 had a high risk of venous thromboembolic events (VTE) (a significant proportion is pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower extremities), in contrast to the heterogeneity of the development of arterial thromboembolic events (ATE) (low rates of development myocardial infarction and stroke). It is important to implement diagnostic and search strategies for early detection of thromboembolism in patients suffering from coronavirus infection. In addition, according to the opinion of most authors, the number of thromboembolic events decreases against the background of taking primary thromboprophylaxis, which is confirmed by a decrease in the percentage of thromboembolic complications in patients with a diagnosis of SARS-CoV-2 infection. Therefore, conducting a more skeptical assessment of the possibility of the development of VTE is important for the prevention of complications of the coronavirus infection. The study of these problems allows us to use the acquired knowledge on the development of thromboembolic events in patients against the background of the incidence of COVID-19 in a more detailed and justified manner and, accordingly, to improve the methods of diagnosis, treatment and prevention of these complications.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PurposeSeveral studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE).MethodsA total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores).ResultsMedian time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses.ConclusionIn hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating.Clinicaltrials.gov IDNCT04377035

Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome

Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.

A Retrospective Review of Outcomes in Intensive Care Unit Patients Infected With SARS-Cov2 in Correlation to Admission Acute Physiologic Assessment and Chronic Health Evaluation II Scores.

IntroductionCoronavirus disease 2019 (COVID-19) has emerged as a global pandemic that has placed an unprecedented burden on intensive care services worldwide. Identification of a reliable risk-stratification tool for COVID-19 patients is necessary for appropriate resource allocation, selection of clinical management pathways, and guidance of goals of care conversations with families and caregivers in the critical care setting. The Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scoring system is one of several predictive models used to classify illness severity and estimate mortality risk on admission to the intensive care unit (ICU). Our retrospective study sought to evaluate the prognostic ability of the APACHE II score in COVID-19 patients according to endpoints of mortality and length of stay (LOS) as well as unfavorable clinical outcomes, including development of acute renal failure (ARF) requiring renal replacement therapy (RRT) and acute venous thromboembolic events (VTE).MethodsThis multicenter retrospective cohort study evaluated a randomized sample of 3,102 patients with confirmed COVID-19 disease admitted to the ICU from January 2020 to May 2020. A total of 395 patients with complete data points for appropriate APACHE II score calculation, absence of the preexisting comorbidities end-stage renal disease, and history of VTE were included. Linear and logistic regression models were employed to evaluate primary outcomes of mortality and LOS as well as secondary outcomes of VTE and ARF requiring continuous renal replacement therapy (CRRT) or hemodialysis (HD).Key resultsAmong the 395 patients enrolled, total percent mortality and mean LOS were 37.0% and 12.92 days, respectively. Primary outcome analysis revealed a statistically significant increase in odds of mortality as well as in mean LOS with every additional point increase in APACHE II score from a baseline of zero. Specifically, for every point increase in the APACHE II score, odds of mortality increased by 12% (p value < 0.001), and average LOS increased by 0.2 days (p value < 0.001). In our secondary outcome analysis, 14.43% and 62.2% of the total sample population developed ARF requiring RRT and VTE, respectively. For every additional point increase in APACHE II score from a baseline of zero, odds of requiring CRRT or HD increased by 10% on average (95% CI (1.06, 1.15); p value < 0.001). Similarly, for every additional point increase in the APACHE II score from a baseline of zero, there was a corresponding increase in odds of VTE by 19% (95% CI (1.14, 1.24); p value < 0.001).ConclusionsThe APACHE II score is an effective predictive model of in-hospital mortality and unfavorable clinical outcomes, including prolonged LOS, ARF requiring CRRT or HD, and development of VTE. As therapeutic interventions for COVID-19 evolve, application of this risk-stratification tool may guide clinical management decisions in the critical care setting.

Biologically Active Tissue Factor-Bearing Larger Ectosome-Like Extracellular Vesicles in Malignant Effusions from Ovarian Cancer Patients: Correlation with Incidence of Thrombosis.

The development of malignant effusions such as ascites reflects a massive progression of a malignant disease. In patients with ovarian carcinoma, a high amount of ascites (>500 mL) is an independent negative prognostic marker. The composition and constituents of ascites reflect the inflammatory environment of the underlying tumor. Increased cellular resistance of ascites-derived tumor cells and the development of venous thromboembolic events (VTE) are major risks for these patients, especially in patients with advanced ovarian carcinoma. In this study, we discuss the release of tissue factor-bearing extracellular vesicles (TF+ EVs) from tumor cells into the environment (ascites fluid) and their systemic spreading as a possible causal explanation of the pathologic coagulation status in these patients. We obtained ascites from patients with advanced ovarian carcinoma, collected during surgery or therapeutic paracentesis (n = 20). Larger ectosome-like EVs were isolated using sequential centrifugation, quantified by high-resolution flow cytometry and analyzed using nanoparticle tracking analysis. Furthermore, the pro-coagulant properties (TF activity) of EVs were determined. Compared to published TF activities of EVs from healthy persons, TF activities of EVs derived from ascites of patients with ovarian cancer were very high, with a median of 80 pg/mL. The rate of VTE, as reported in the patient files, was high as well (35%, 7 out of 20). Furthermore, all but one patient with VTE had EV concentrations above the median within their ascetic fluid (p < 0.02). Since VTE continues to be a frequent cause of death in cancer patients, prophylactic antithrombotic treatment might be worth considering in these patients. However, given the risk of bleeding, more clinical data are warranted. Although the study is too small to enable reaching a conclusion on direct clinical implementation, it can well serve as a proof of principle and a rationale to initiate a prospective clinical study with different patient subgroups. We also show ex vivo that these larger ectosome-like EVs induce intracellular ERK phosphorylation and tumor cell migration, which is not directly related to their pro-coagulative potency, but might help to understand why cancer patients with thromboembolic events have a poorer prognosis.

Predicting Venous Thromboembolic Events in Patients with Coronavirus Disease 2019 Requiring Hospitalization: an Observational Retrospective Study by the COVIDIC Initiative in a Swiss University Hospital.

Background Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events (VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods. We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020. Results Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value > 3,120 ng/ml (P < 0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation (P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value ≥ 3,000 ng/l combined with a Wells score for PE ≥ 2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value > 5,611 ng/ml (P < 0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation (P < 0.001; OR 5.9, 95% CI 2.3-15.1). Conclusions VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells ≥ 2 score and D − dimer ≥ 3,000 ng/l is a good predictor of VTE at admission.

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

MP49-01 PREDICTORS OF THROMBOSIS IN TESTICULAR CANCER DURING PLATINUM-BASED CHEMOTHERAPY

INTRODUCTION AND OBJECTIVES:Testicular cancer patients receiving platinum-based chemotherapy are at risk for the development of venous thromboembolic events. In this study, we aim to identify poten...

86 Incidence and Patient Characteristics for the Development of Venous Thromboembolic Events within the Adult Burn Center Population and an Evaluation of the Caprini Risk Assessment Model

86 Incidence and Patient Characteristics for the Development of Venous Thromboembolic Events within the Adult Burn Center Population and an Evaluation of the Caprini Risk Assessment Model

Hypercoagulability and Risk of Venous Thromboembolic Events in Endogenous Cushing's Syndrome: A Systematic Meta-Analysis.

Background: Hypercortisolism has been implicated in the development of venous thromboembolic events (VTE). We aimed to characterize VTE risk in endogenous Cushing's syndrome (CS) patients, compare that risk to other pathologies, and determine if there are any associated coagulation factor changes.Methods: Medline and Scopus search for “hypercortisolism” and “thromboembolic disease” from January 1980 to April 2017 to include studies that reported VTE rates and/or coagulation profile of CS patients. A systematic review and meta-analysis were performed.Results: Forty-eight studies met inclusion criteria. There were 7,142 CS patients, average age was 42 years and 77.7% female. Odds ratio of spontaneous VTE in CS is 17.82 (95%CI 15.24–20.85, p < 0.00001) when comparing to a healthy population. For CS patients undergoing surgery, the odds ratio (both with / without anticoagulation) of spontaneous VTE is 0.26 (95%CI 0.07–0.11, p < 0.00001)/0.34 (0.19–0.36, p < 0.00001) when compared to patients undergoing hip fracture surgery who were not treated with anticoagulants. Coagulation profiles in patients with CS showed statistically significant differences compared to controls, as reflected by increases in von Willebrand factor (180.11 vs. 112.53 IU/dL, p < 0.01), as well as decreases in activated partial thromboplastin time (aPTT; 26.91 vs. 30.65, p < 0.001) and increases in factor VIII (169 vs. 137 IU/dL, p < 0.05).Conclusion: CS is associated with significantly increased VTE odds vs. general population, but lower than in patients undergoing major orthopedic surgery. Although exact timing, type, and dose of anticoagulation medication remains to be established, clinicians might consider monitoring vWF, PTT, and factor VIII when evaluating CS patients and balance advantages of thromboprophylaxis with risk of bleeding.

Predictors of thrombosis in testicular cancer during platinum-based chemotherapy.

To identify potential risk factors for the development of venous thromboembolic events in testicular cancer patients receiving platinum-based chemotherapy. We performed a retrospective analysis including 255 patients with testicular germ cell tumors who received platinum-based chemotherapy from 2003 to 2018 as a multi-center observational cohort study. Patient and tumor characteristics of patients with and without a thromboembolic event were analyzed. 49 (19%) patients experienced a venous thromboembolic event, with the majority representing pulmonary embolism and deep venous thrombosis (47%). There were no significant differences regarding the development of a venous thromboembolic event between first- and second-line regimes. Multivariate analysis showed an increased risk for a venous thromboembolic event in patients with clinical stage ≥ IIC disease (OR 2.259 [95% CI 1.105-4.618], p = 0.026), elevated serum LDH (OR 2.162 [95% CI 1.018-4.593], p = 0.045), febrile neutropenia (OR 2.973 [95% CI 1.363-6.487], p = 0.006) and central venous access (OR 3.465 [95% CI 1.068-11.243], p = 0.039). Patients suffering from a venous thromboembolic event revealed a significantly reduced overall survival (p = 0.033) during a median follow-up of 8months [IQR 2-18]. 19% of all patients treated by platinum-based chemotherapy due to testicular cancer suffered from a venous thromboembolic event, associated with reduced overall survival. As a result, monitoring of cancer patients at risk as well as the improvement of patients' awareness of a thromboembolic event should thus be the main goal of their treating physicians.

Leukocyte Subtypes As Predictors for Venous Thromboembolism in Diffuse Large B-Cell Lymphoma

Introduction: Venous thromboembolic events (VTE) are a frequent complication of patients diagnosed with diffuse large B -cell lymphoma (DLBCL). Development of VTE portends poor prognosis. Previous studies have identified use of anthracyclines, advanced stage at presentation, obesity, and development of neutropenia and anemia after first cycle of chemotherapy as risk factors for VTE. Recent studies suggest leukocyte subpopulations may affect the risk of VTE; elevated neutrophil and monocyte counts have been associated with increased risk of VTE in solid malignancy patients. The role of leukocyte subpopulations in VTE risk in DLBCL patients has not yet been evaluated. We conducted a retrospective study to identify risk factors for VTE and specifically address the role of leukocytes and their subtypes in VTE risk assessment in DLBCL.Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics, baseline laboratory and disease information, as well as treatment details. Patient records were reviewed for the presence of VTE, including radiographic confirmation. Progression free survival and overall survival were calculated from time of diagnosis using Kaplan Meier methodology, comparisons were done with log rank. Cumulative incidence of VTE was calculated considering death as competing risk. Univariate Cox regression analysis was conducted for baseline characteristics, risk factors and baseline laboratory parameters. Variables with a univariate p value lower than 0.1 were included in multivariate Cox regression. All analyses were performed using XLSTAT (Addinsoft, NY).Results: A total of 542 patients were included in the study. Baseline characteristics are described in Table 1. At a median follow up of 48 months, 93 patients developed VTE, with 1 and 2 -year cumulative incidence of VTE of 13.5% (95% CI 10.9-16.8) and 20.5% (95% CI 17.3-24.3). In subsequent years, VTE risk increased more modestly, reaching 23.6% at 4 years (95% CI 20.2-27.7). Eighty percent of VTE occurred in patients with active disease. Sixteen percent of VTE were pulmonary embolism (PE), 53% were lower extremity deep vein thrombosis (DVT), and 31% upper extremity DVTs. Approximately 55% of upper extremity DVTs were line - related.On univariate analysis (table 2), the risk factors with statistically significant odds for increased hazard of VTE included previous history of VTE, albumin less than 3 gm/dl, leukocyte count greater than 11,000/mcl, hemoglobin less than 12 gm/dl, absolute neutrophil count (ANC), ANC to absolute lymphocyte ratio (ANC: ALC) higher than 2.5 and presence of bulky disease at the time of diagnosis. In multivariate analysis, BMI > 35, bulky disease and ANC/ALC ratio ≥ 2.5 remained statistically significant risk factors for development of VTE.Presence of VTE at any time after DLBCL diagnosis was also associated with worse overall survival (OS) and progression free survival (PFS) rates. Patients with VTE after diagnosis had an estimated 4 - year OS of 50.6 % (95% CI 39.7-61.6) vs. 71.3% (95% CI 66.9-75.7) in patients without VTE (p<0.0001) (figure 1). Four-year PFS estimates were 37.5% (95 % CI 27.1-48) and 60% (95 % CI 55.3-64.7), respectively (p<0.0001) (figure 2).Conclusion: VTE is a frequent complication in DLBCL patients and is associated with increased mortality and risk of progressive disease. The first 24 months after DLBCL diagnosis appear to be the time of highest VTE risk, likely a consequence of active disease, treatment and other risk factors such as indwelling catheters. Leukocyte subpopulations appear to have a correlation with VTE risk; the ANC: ALC ratio is a measure of systemic inflammatory response, and in DLBCL patients, a ratio above 2.5 is correlated with increased risk of VTE. Incorporation of this laboratory measurement to currently available VTE risk assessment tools may help more precisely identify the at highest risk of VTE. DisclosuresMalek:Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau. Tomlinson:Foundation Medicine: Consultancy. Caimi:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees.

MP04-02 LONG TERM INCIDENCE OF VENOUS THROMBOEMBOLIC EVENTS FOLLOWING CYSTECTOMY: A POPULATION-BASED ANALYSIS.

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2017MP04-02 LONG TERM INCIDENCE OF VENOUS THROMBOEMBOLIC EVENTS FOLLOWING CYSTECTOMY: A POPULATION-BASED ANALYSIS. Christopher Wallis, Diana Magee, Raj Satkunasivam, and Robert Nam Christopher WallisChristopher Wallis More articles by this author , Diana MageeDiana Magee More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , and Robert NamRobert Nam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.140AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. METHODS We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. RESULTS Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Figure). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. CONCLUSIONS Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. © 2017FiguresReferencesRelatedDetailsCited byKlaassen Z, Arora K, Goldberg H, Chandrasekar T, Wallis C, Sayyid R, Fleshner N, Finelli A, Kutikov A, Violette P and Kulkarni G (2017) Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current GuidelinesJournal of Urology, VOL. 199, NO. 4, (906-914), Online publication date: 1-Apr-2018. Volume 197Issue 4SApril 2017Page: e28-e29 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Christopher Wallis More articles by this author Diana Magee More articles by this author Raj Satkunasivam More articles by this author Robert Nam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term incidence of venous thromboembolic events following cystectomy: A population-based analysis.

288 Background: Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. Methods: We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. Results: Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Table 1). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. Conclusions: Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. [Table: see text]

Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides.

To assess potential associations for the development of venous thromboembolic events in patients with ANCA-associated vasculitides (AAV). Four hundred and seventeen patients enrolled to participate in randomized controlled trials conducted by the European Vasculitis Society were identified. Univariate and multivariate analyses were performed to validate previously proposed and identify novel risks associated with venous thromboembolism (VTE) in AAV. VTE occurred in 41 of 417 (9.8%) patients. Uncorrected univariate analysis identified BVAS (odds ratio, OR = 1.05, 95% CI: 1.01, 1.10; P = 0.013), subsequent development of malignancy (OR = 2.6, 95% CI: 1.19, 5.71; P = 0.017), mucous membrane or eye involvement (OR = 2.13, 95% CI: 1.10, 4.11; P = 0.024) and baseline creatinine (OR = 1.08, 95% CI: 0.99, 1.18; P = 0.037) as being associated with the development of VTE. Multivariate analysis highlighted CRP (per 10 mg/l increase, OR = 1.05, 95% CI: 1.01, 1.09; P = 0.025), cutaneous involvement (OR = 4.83, 95% CI: 1.63, 14.38; P = 0.005) and gastrointestinal involvement (OR = 6.27, 95% CI: 1.34, 29.37; P = 0.02) among the BVAS items as well as baseline creatinine (per 100 µmol/l increase, OR = 1.17, 95% CI: 1.02, 1.35; P = 0.029) as being associated with VTEs. Our results highlight a role of CRP, baseline creatinine, and cutaneous and gastrointestinal involvement in the risk stratification as being associated with thromboembolic events. Moreover, there might be an association between VTEs and subsequent development of malignancy and disease activity in general.

Portomesenteric Vein Thrombosis After Excision of Parasitic Peritoneal Myomas

An enlargement of multiple asymptomatic pelvic masses was detected during a regular checkup of a 39-year-old woman. Twelve years earlier, she had undergone laparoscopic-assisted myomectomy, at which time an uncontained manual extraction of a posterior intramural myoma was performed. This was followed by 2 uneventful cesarean deliveries after spontaneous conceptions. Diagnostic imaging revealed at least 3 abdominal masses, 1 of which received its major blood supply from the inferior mesenteric artery. Gasless single-port laparoscopic excision of the peritoneal masses, was performed along with laparoscopic-assisted vaginal hysterectomy and bilateral salpingo- oophorectomy. The masses were histopathologically diagnosed as parasitic peritoneal myomas. The patient's immediate postoperative course was uneventful; however, on day 6 after surgery, she complained of severe periumbilical abdominal pain and vomiting. Anticoagulant therapy was initiated after hematologic examination revealed an elevated D-dimer level and dynamic computed tomography angiography showed portomesenteric vein thrombosis. Vaginal stump bleeding, which occurred 17 days after the initiation of anticoagulant therapy, was managed conservatively, and there was no recurrence of venous thrombosis in the year after surgery. To avoid significant morbidities and potential mortality when parasitic peritoneal myomas with aberrant neovascularization are excised, attention should be given to the perioperative development of venous thromboembolic events in rare locations.