Burden Of Venous Thromboembolism Research Articles

Trends in Venous Thromboembolism and Chemoprophylaxis Utilization in Elective Total Knee Arthroplasty from 2011 to 2020

Venous thromboembolism (VTE) is a feared complication of joint arthroplasty, leading to recent clinical practice guidelines (CPGs) aimed at VTE prevention and prophylaxis. However, limited studies have examined national changes in practice regarding chemoprophylaxis and the resultant changes in VTE rates. The purpose of this study was to identify: 1) the temporal trends in thrombotic complications; and 2) changes in chemoprophylaxis utilization in patients undergoing elective TKA. A retrospective study was conducted using a large all-payer claims dataset. Patients who underwent osteoarthritis-indicated TKA between 2011 and 2020 were identified. Annual rates of VTE, including deep vein thrombosis (DVT), and pulmonary embolism (PE), within 90 days of TKA were determined. Utilization patterns for postoperative aspirin and anticoagulant medications were observed. Temporal trends were analyzed with linear regression and the calculation of the cumulative annual growth rate (CAGR). Multivariable logistic regression was conducted to account for the effects of age and comorbidities. A total of 1,263,351 TKA patients were identified between 2011 and 2020. There were significant reductions in VTE rates (2.9% in 2011 to 1.8% in 2020), DVT rates (2.0% in 2011 to 1.3% in 2020), and PE rates (1.1% in 2011 to 0.6% in 2020). Postoperative utilization of aspirin increased from 5.9% in 2011 to 53.2% in 2020, whereas utilization of anticoagulants decreased from 94.1% in 2011 to 46.8% in 2020. Among anticoagulants, direct factor Xa inhibitors had the greatest increase in utilization (4.6 to 69.7%). The average reimbursement-associated with VTE after TKA decreased from $18,061 in 2011 to $7,835 in 2020. The incidence rate and economic burden of VTE after TKA have significantly declined since 2011. There has been a trend toward increased aspirin and direct oral anticoagulant utilization for postoperative chemoprophylaxis.

Venous Thrombosis in Airborne Viral Infections: Is Coronavirus Disease 2019 now Any Different from Influenza?

One of the hallmarks of coronavirus disease 2019 (COVID-19), particularly in complicated cases (i.e., requiring hospitalization or intensive care support), is persistent hemostasis activation, which may be associated with a vast array of thrombotic episodes involving both the arterial and venous systems. The renewed emphasis on the relationship between viral infections and venous thrombosis paves the way for determining whether a more common and often underestimated infection disease, such as influenza, may also be associated with a significant burden of venous thrombotic episodes, and how this eventual thrombotic risk compares to that seen in COVID-19, both in the past and with newer variants. Our review of studies comparing the burden of venous thromboembolism (VTE) in patients with COVID-19 or influenza revealed that the thrombotic risk appears to be significantly higher in patients with COVID-19 but remains certainly not meaningless in those with influenza, particularly in subjects infected by highly virulent strains (i.e., H1N1), in those who develop pneumonia and require intensive care support. In these specific clinical settings, the adoption of tailored thromboprophylaxis may be indicated though more studies are compellingly needed on this matter. As COVID-19 variants emerge, there is a possibility that the VTE burden of COVID-19 will decrease, and progress to that of other respiratory viruses.

Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease

AbstractHospitalized patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE). We aimed to evaluate the effectiveness and safety of prophylactic anticoagulation compared with no anticoagulation in hospitalized patients with IBD. We conducted a retrospective cohort study using a hospital-based database. We included patients with IBD who had a length of hospital stay ≥2 days between 1 January 2016 and 31 December 2019. We excluded patients who had other indications for anticoagulation, users of direct oral anticoagulants, warfarin, therapeutic-intensity heparin, and patients admitted for surgery. We defined exposure to prophylactic anticoagulation using charge codes. The primary effectiveness outcome was VTE. The primary safety outcome was bleeding. We used propensity score matching to reduce potential differences between users and nonusers of anticoagulants and Cox proportional-hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 56 194 matched patients with IBD (users of anticoagulants, n = 28 097; nonusers, n = 28 097). In the matched sample, prophylactic use of anticoagulants (vs no use) was associated with a lower rate of VTE (HR, 0.62; 95% CI, 0.41-0.94) and with no difference in the rate of bleeding (HR, 1.05; 95% CI, 0.87-1.26). In this study of hospitalized patients with IBD, prophylactic use of heparin was associated with a lower rate of VTE without increasing bleeding risk compared with no anticoagulation. Our results suggest potential benefits of prophylactic anticoagulation to reduce the burden of VTE in hospitalized patients with IBD.

Which Procedures Contribute Most to the System-Wide Burden of Postoperative Venous Thromboembolism?

While clinical risk assessment models examine patient-level characteristics that portend morbidity, there is a paucity of literature exploring which procedures contribute most to the system-wide burden of venous thromboembolism (VTE). We aimed to identify highly contributory procedures as potential targets for quality improvement. All patients in the 2020 National Surgical Quality Improvement Program (NSQIP) Public User File were included. Current Procedural Terminology (CPT) codes were analyzed individually and grouped by National Healthcare Safety Network groupings. We counted prevalence of VTE and calculated VTE rate for each CPT and for each grouping. Of 902,968 included patients, 7501 (.83%) sustained postoperative VTE. Of 2748 unique CPT codes, VTE occurred for 762 (28%). Twenty procedure codes (.7%) contributed 39% of the total VTE. VTE rates of these procedures ranged from high-volume procedures with low VTE rates such as laparoscopic cholecystectomy (.25%) and laparoscopic hysterectomy (.32%) to lower volume procedures with high VTE rate such as Hartmann's procedure (4.32%), Whipple procedure (3.85%), and distal pancreatectomy (3.82%). The CPT grouping with the most VTE was colon surgeries (1275/7501). A small number of procedures contributes to the system-wide burden of VTE. High-risk procedures are important targets for standardized prophylaxis protocols. For low-risk procedures, careful attention should be paid to patient-specific factors that may increase VTE risk such as obesity, cancer, or limited mobility, as many common procedures contribute greatly to the systemic burden of VTE. Overall, surveillance can perhaps be targeted on a smaller number of procedures, allowing for more efficient use of quality improvement resources.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Venous thromboembolism in metastatic pancreatic cancer.

Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC). A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan-Meier survival plots and Cox proportional hazards regressions. 400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0-1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non-VTE group. Only advanced stage (OR 3.7, p = .001) correlated with increased VTE risk. The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis.

Inpatient Burden, Characteristics and Outcomes Associated with Venous Thrombotic Complications Among Patients with Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal hematopoietic stem cell disease caused by mutations in an X-linked gene called phosphatidylinositol glycan class A (PIG-A). Venous thromboembolism (VTE) is known to be a leading cause of death in patients with PNH and is considered to be a clinical emergency, warranting treatment with eculizumab and therapeutic anticoagulation. Although several studies have analyzed the overall disease burden and predictors of outcomes associated with VTE in patients with PNH, data on inpatient burden and outcomes are scarce. We sought to investigate the inpatient burden, characteristics and overall outcomes associated with VTE-related complications among patients with PNH using a large nation-wide database. Methods: The current nation-wide retrospective analysis was conducted using the National Inpatient Sample (NIS), which includes administrative and demographic data from a 20% sample of inpatient hospitalizations in the United States. We interrogated the NIS for admissions among patients with PNH from 2016-2019 using appropriate ICD-10 diagnosis codes. Admissions with known hypercoagulable conditions such as anti-phospholipid antibody syndrome, factor V Leiden mutation, prothrombin gene mutation, protein C and S deficiency, etc. were excluded. Hospitalizations with PNH were further assessed for VTE-related complications using appropriate ICD-10 codes and data on baseline characteristics and inpatient outcomes were collected and analyzed. Chi-square test was used for categorical data and Student's t-test was used for continuous variables. A p-value < 0.05 was considered statistically significant. SAS version 9.4 (SAS Institute Inc.) was used for statistical analysis. Results: A total of 3,600 hospitalizations were included for analysis, out of which, 345 (9.6%) were associated with VTE. Lower extremity deep vein thrombosis (DVT) was noted to be the most common (100/345, 29%) followed by hepatic vein thrombosis/ Budd Chiari syndrome (80/345, 23.2%), portal vein thrombosis (70/345, 20.3%), pulmonary embolism (60/345, 17.4%), upper extremity DVT (60/345, 17.4%), non-specific VTE (15/345, 4.3%) and renal vein thrombosis (5/345, 1.5%). Table 1 shows baseline characteristics and co-morbidities in hospitalizations associated with and without VTE. Patients in the VTE group were significantly younger (47.3±17.4 vs 50.4±22.1, p=0.01) and had a higher prevalence of co-morbid obesity (27.5% vs 10.1%, <0.001) and chronic liver disease (23.2% vs 8.3%, p<0.001). The prevalence of myelodysplastic syndrome (5.8% vs 11.4%, p=0.002) and aplastic anemia (20.3% vs 27.2%, p=0.006) was noted to be significantly lower in the VTE group, while no difference was noted with iron deficiency anemia (4.3% vs 4.1%, p=0.85) and primary myelofibrosis (2.9% vs 1.5%, p=0.06). No patients with acute myeloid leukemia could be captured in our cohort in either of the groups. Overall, there was no difference in all-cause inpatient mortality between groups with and without VTE (1.4% vs 2.5%, p=0.24), however, hospitalizations with VTE-related complications were associated with longer average length of stay (10 days vs 6.3 days, p<0.001), higher average cost of hospitalizations ($178,143 vs $100,547, p<0.001) and lower rate of discharge to home (66.7% vs 72.5%, p=0.02). Conclusions: Overall, 10% of the hospitalizations in our analysis were associated with VTE, out of which, lower extremity DVT, hepatic and portal vein thrombosis were the most common sites (approximately 75% of the VTE burden). Patients with VTE were younger and had a higher prevalence of co-morbid obesity and chronic liver disease. Prevalence of myelodysplastic syndrome and aplastic anemia was noted to be significantly lower in the VTE group, however, further prospective clinical data are needed to analyze the impact of these diagnoses on overall risk of VTE in patients with PNH. Although VTE did not appear to increase all-cause inpatient mortality; associated increase in average length of stay, average cost of hospitalization and decreased likelihood of discharge to home were noted. Concerted efforts to strengthen and enhance care for patients with PNH in the ambulatory setting are needed to prevent inpatient hospitalizations with VTE and reduce associated healthcare burden and costs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Preventability of venous thromboembolism in hospitalised patients.

Hospital-acquired venous thromboembolism (VTE) is a major cause of morbidity and mortality. To determine the proportion of patients with hospital-acquired VTE that are preventable. This was a retrospective study of patients in two tertiary care hospitals in Sydney, Australia. Data were collected for patients with hospital-acquired VTE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) coding from January 2018 to May 2020. Patients were classified as low, moderate or high risk of developing a VTE during hospitalisation based on demographic and clinical factors. A hospital-acquired VTE was considered to be potentially preventable if there was suboptimal prophylaxis in the absence of contraindications. Suboptimal therapy included at least one of the following related to VTE prophylaxis: low dose, missed dose (prior to developing a VTE), suboptimal drug and delayed start (>24 h from admission). There were 229 patients identified with VTE based on ICD-10-AM coding. A subset of 135 patients were determined to have actual hospital-acquired VTE. Of these, there were no patients at low risk, 64% (87/135) at moderate risk and 44% (48/135) at high risk of developing a VTE. Most (65%; n = 88/135) patients had one or more contraindications to receive recommended prophylaxis. Overall, the proportion of patients who received suboptimal prophylaxis was 11% (15/135). Approximately one out of 10 hospital-acquired VTE are preventable. Hospitals should focus on measuring and reporting VTE that are preventable to provide a more accurate measure of the burden of VTE that can be reduced by improving care.

Characteristics and Predictors of Venous Thromboembolism Among Lymphoma Patients Undergoing Chemotherapy: A Cohort Study in China.

Background: Venous thromboembolism (VTE) is a potential complication among lymphoma patients. We evaluated the incidence rate and predictors of VTE in lymphoma patients undergoing chemotherapy. Methods: The present study retrospectively studied 1,069 patients with lymphoma who were treated with chemotherapy from 2018 to 2020. We investigated clinical predictors of VTE among all patients. The follow-up results were obtained via telephone communication and from inpatient and outpatient records. Results: A total of 1,069 patients underwent chemotherapy for lymphoma. During a mean follow-up of 23.1 months, 52 (4.9%) patients developed VTE. According to a multivariate analysis, the five variables found to be independently associated with VTE were male sex (HR 2.273, 95% CI 1.197–4.316, p = 0.012), age >64-years-old (HR 2.256, 95% CI 1.017–5.005, p = 0.045), the number of cycles of chemotherapy (HR 4.579, 95% CI 1.173–17.883, p = 0.029), platelet count ≥350 × 109/L (HR 2.533, 95% CI 1.187–5.406, p = 0.016), and D-dimer >0.5 mg/L (HR 4.367, 95% CI 2.124–8.981, p < 0.001). Conclusion: This population-based study confirms the risk factors for VTE among patients with lymphoma who underwent chemotherapy and confirms that targeted thromboprophylaxis may reduce the burden of VTE in this population.

Readmissions From Venous Thromboembolism After Complex Cancer Surgery

Venous thromboembolism (VTE) is a major cause of preventable morbidity and mortality after cancer surgery. Venous thromboembolism events that are significant enough to require hospital readmission are potentially life threatening, yet data regarding the frequency of these events beyond the 30-day postoperative period remain limited. To determine the rates, outcomes, and predictive factors of readmissions owing to VTE up to 180 days after complex cancer operations, using a national data set. A retrospective cohort study of the 2016 Nationwide Readmissions Database was performed to study adult patients readmitted with a primary VTE diagnosis. Data obtained from 197 510 visits for 126 104 patients were analyzed. This was a multicenter, population-based, nationally representative study of patients who underwent a complex cancer operation (defined as cystectomy, colectomy, esophagectomy, gastrectomy, liver/biliary resection, lung/bronchus resection, pancreatectomy, proctectomy, prostatectomy, or hysterectomy) from January 1 through September 30, 2016, for a corresponding cancer diagnosis. Readmission with a primary diagnosis of VTE. Proportion of 30-, 90-, and 180-day VTE readmissions after complex cancer surgery, factors associated with readmissions, and outcomes observed during readmission visit, including mortality, length of stay, hospital cost, and readmission to index vs nonindex hospital. For the 126 104 patients included in the study, 30-, 90-, and 180-day VTE-associated readmission rates were 0.6% (767 patients), 1.1% (1331 patients), and 1.7% (1449 of 83 337 patients), respectively. A majority of patients were men (58.7%), and the mean age was 65 years (SD, 11.5 years). For the 1331 patients readmitted for VTE within 90 days, 456 initial readmissions (34.3%) were to a different hospital than the index surgery hospital, median length of stay was 5 days (IQR, 3-7 days), median cost was $8102 (IQR, $5311-$10 982), and 122 patients died (9.2%). Independent factors associated with readmission included type of operation, scores for severity and risk of mortality, age of 75 to 84 years (odds ratio [OR], 1.30; 95% CI, 1.02-1.78), female sex (OR, 1.23; 95% CI, 1.11-1.37), nonelective index admission (OR, 1.31; 95% CI, 1.03-1.68), higher number of comorbidities (OR, 1.30; 95% CI, 1.06-1.60), and experiencing a major postoperative complication during the index admission (OR, 2.08; 95% CI, 1.85-2.33). In this cohort study, VTE-related readmissions after complex cancer surgery continued to increase well beyond 30 days after surgery. Quality improvement efforts to decrease the burden of VTE in postoperative patients should measure and account for these late VTE-related readmissions.

Incidence of venous thromboembolism in rheumatoid arthritis, results from a "real-life" cohort and an appraisal of available literature.

Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our “real-life” cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic.We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk. Possible predictive factors were also exploited by regression analyses. Available literature about this topic was also assessed.In this evaluation, 347 consecutive patients without previous evidence of VTE, attending our Rheumatologic Clinic from 2010 to 2020, were studied. In our “real-life” cohort, the incidence proportion of VTE was 3.7% (2.7–4.7%) and considering over 1654 person-years, an incidence rate of 7.8 × 1000 (2.5–11.7). Exploratively assessing predictive factors in our cohort, older age (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01–1.14, p = .015), higher body mass index (HR 1.37, 95% CI 1.04–1.80, P = .026), and longer disease duration (HR 1.11, 95% CI 1.03–1.20, P = .006) resulted to be significant predictors of VTE occurrence during the follow-up.In our “real-life” cohort, VTE burden has been suggested in patients with RA. Comparing our results with previous data derived from randomized controlled trials and administrative data, some different findings were retrieved about incidence of VTE. Assessing predictive factors, older age, higher body mass index, and longer disease duration resulted to be significant predictors of VTE occurrence during the follow-up. Taking together these observations, a further evaluation of this issue on specific designed studies is needed to provide more generalizable results to the daily clinical practice.

A Roadmap to Implementing Venous Thromboembolism Risk Stratification and Mitigation.

Venous thromboembolism (VTE) is a life-threatening postoperative complication that carries high morbidity and mortality for plastic surgery patients. In 2011, the American Society of Plastic Surgeons recommended the adoption of a VTE risk stratification and mitigation; however, successful implementation of VTE prophylaxis protocols has not been well described. To address and reduce the VTE burden at our academic center, a risk assessment protocol was implemented for patients undergoing outpatient plastic surgery procedures. All patients who received outpatient plastic surgery between August 2018 and July 2019 were eligible for the VTE modified Caprini risk assessment screening. Sampling of practice patterns was done by chart review from the first week of each month. The study was divided into 3 phases to assess the relationship of screening compliance rates with each protocol change. Compliance was defined as completion of VTE Caprini screening with documentation in patients' charts. Over the 12-month study period, 277 patients met the inclusion criteria. From August to November 2018 (phase 1), patients were screened at the initial clinic visit with an average compliance rate of 11.1%. In December 2018 (phase 2), patients were screened on the day of surgery, with an average compliance rate of 47.1%. From January to July 2019 (phase 3), surgeons recorded the numerical Caprini score into the patient's electronic medical record with a subsequent compliance rate of 61.3%. The overall compliance during the 12 months was 44.8%. The median calculated Caprini score for this population was 4 (range, 1-7). Standardization of VTE risk assessment is vital for patient safety and outcomes. Successful implementation and long-term protocol sustainability are not a simple goal. In this study, protocol compliance greatly improved after tailoring the guidelines to the specific institutional needs and workflow. These results reinforce the importance of continuous protocol review and modification to ensure optimal departmental buy-in and sustainability.

Venous Thromboembolism (VTE) Increases the Healthcare Burden in Patients with Malignant Glioma (MG)

Background: The cumulative incidence of symptomatic venous thromboembolism (VTE) among patients with malignant glioma (MG) is high, with estimates ranging from 20-35% during the course of therapy. VTE is the second leading cause of death among ambulatory patients receiving cancer chemotherapy, with a 2-fold or greater increase in mortality compared to those without VTE, even after adjusting for stage. Specific to MG patients, Semrad et al. reported a higher likelihood of death at 2-year follow up (hazard ratio 1.3). The development of VTE is associated with increased mortality, an increased risk of hospitalization, delays in cancer treatment and an increased risk of complications including pain, bleeding, and bruising from high dose therapeutic anticoagulation. As a result, the economic burden of VTE in cancer patients is substantial and is associated with a nearly 2 fold increase in cost. Data regarding VTE burden encompasses all cancer types and additional data is needed to characterize VTE burden in specific cancer types, particularly rarer cancers. The aim of this study was to assess the healthcare burden associated with the development of VTE in MG patients.Methods: A retrospective chart review of patients with MG at an academic medical center was conducted from 2009-2016. Patients 18 years and older with a histologic diagnosis of malignant glioma, WHO grade 3-4 were assessed. A total of 31 patients were identified and information was collected with respect to their healthcare consumption as related to their oncologic care. Specifically, the number of office visits, emergency room visits, inpatient hospitalizations with the associated costs of VTE management and it's complications were collected. Using SPSS, linear regression models and descriptive statistics were used to determine the relationship between the development of VTE and healthcare consumption.Results: Of the 31 patients in the study, 10 developed VTE (32%). All patients who developed a VTE were placed on therapeutic anticoagulation as part of VTE management. Fifty percent of patients developed complications related to anticoagulation, including gastrointestinal, retroperitoneal and intracranial bleeding events. One patient required placement of an IVC filter after experiencing a bleeding complication. Patients that developed VTE had an increase in inpatients days (21.3 inpatients days) as compared to their non-VTE counterparts (10 inpatient days), (p=.04). There was a trend towards increased utilization of the emergency room with an average of 5.1 visits in those patients with VTE as compared to those without (2.89), (p=0.244). A limited cost analysis found that anticoagulation management alone generated an additional $84,335 in healthcare costs with an average of $8,433 per patient. A full cost analysis is currently underway.Discussion: The development of VTE in patients with malignant glioma increases inpatient admissions days and pharmaceutical costs related to anticoagulation. While limited in patient number, this represents the first assessment of health care burden associated with VTE specific to this cancer patient population. Given the significant number of MG patients who develop VTE (approximately 1/3 in this study), increases in health care burden are magnified in this patient population and studies are needed to prevent VTE in this particular group of patients. DisclosuresNo relevant conflicts of interest to declare.

Burden of venous thromboembolism in patients with pancreatic cancer.

Pancreatic cancer (PC) is a devastating malignancy with fewer than 10% of patients being alive at 5 years after diagnosis. Venous thromboembolism (VTE) occurs in approximatively 20% of patients with PC, resulting in increased morbidity, mortality and significant health care costs. The management of VTE is particularly challenging in these frail patients. Adequate selection of the most appropriate anticoagulant for each individual patient according to the current international guidelines is warranted for overcoming treatment challenges. The International Initiative on Thrombosis and Cancer multi-language web-based mobile application (downloadable for free at www.itaccme.com) has been developed to help clinicians in decision making in the most complex situations. In this narrative review, we will discuss the contemporary epidemiology and burden of VTE in PC patients, the performances and limitations of current risk assessment models to predict the risk of VTE, as well as evidence from recent clinical trials for the primary prophylaxis and treatment of cancer-associated VTE that support up-dated clinical practice guidelines.

PCV65 Analysis of Venous Thromboembolism (VTE) Hospital Management from Real-World French Administrative Database

Venous thromboembolism (VTE) is caused by the formation of a thrombus in the bloodstream. VTE includes deep vein thrombosis, which can evolve to embolism if the thrombus breaks off. VTE is a frequent pathology, with an annual incidence of 1 to 2 per 1,000 inhabitants in France and a severe pathology, with a 3-month mortality between 10 and 15%. However very few real-world data are available in France on those patients and their hospital management. A retrospective cross-sectional study was conducted using the French exhaustive National hospital discharge database (PMSI). VTE patients were included between 2014 and 2017 and followed until 2018. The study was conducted for the whole VTE population and on two distinct cohorts: (i) patients with venous thrombosis (I80*, I820 I821, I636, I676, O222, O223, O225, O870, O871 and O873) and (ii) patients with embolism (I26*, I822, I823, I828, I829 and O882). Relevant comorbidities were assessed using also ICD-10 codes. Incidence and prevalence of VTE inpatients were calculated and hospital management and its associated costs were described. In-hospital mortality was assessed using Kaplan-Meier model. The number of VTE patients increased from 133,633 to 143,873 between 2014 and 2017 with more than 90% of incident patients. The prevalence and incident rates were stable at 2 per 1,000 inhabitants. Median age was 71 and 52.7% were female. Median length of first VTE episode was 6 days and a recurrence lasted 2 days. The median delay between first and second episode was 354 days. The burden of VTE reached 238.8M€ in 2017. The 1-year hospital mortality was 5.11%. This study provides a recent and detailed description of VTE patients and their hospital management in France. VTE patients hospital management was found to be associated with a high economic burden, mainly caused by the first hospital stay.

Risk Assessment and Management of Venous Thromboembolism in Cancer Patients: A Population-Based Cohort Study

Introduction: The risk of venous thromboembolism (VTE) is increased in cancer patients, compared to subjects without cancer. The Khorana score (KS) is used to stratify VTE risk in cancer outpatients and recent society guidelines recommend thromboprophylaxis for patients with KS≥2. The burden of VTE in cancer, current use of thromboprophylaxis and performance of the KS in the Israeli setting are lacking. This data is needed to drive health-care policies regarding risk stratification and thromboprophylaxis. Aim: Define the clinical need for thromboprophylaxis in an Israeli population of cancer outpatients by determining the cumulative VTE incidence, VTE risk factors and anticoagulation (AC) use. Methods: This retrospective cohort study was conducted using the comprehensive computerized patient-level databases of Maccabi Healthcare Services (MHS), a nationwide healthcare insurer-provider organization for a quarter of the population in Israel, including 2.4 million members. All newly diagnosed cancer patients aged ≥18 years identified from the MHS cancer registry (excluding non-melanoma skin cancer) who initiated systemic anti-cancer treatment between 2010 and 2018 were included in the study. The cancer registry includes patients with cancer diagnostic codes from the Israel Ministry of Health, linked to cancer medication approvals and pathology reports. Subjects with prior VTE or AC within 3 months prior index were excluded. Patients were indexed on the first day of anti-cancer treatment and baseline variables were extracted, as well as data on AC post-index. The KS was used to stratify VTE risk as low (0-1) or high (≥2) at index. The main outcome was VTE at any site, defined using a validated algorithm based on diagnostic codes and AC prescription data (Sanfilippo et al, Thrombosis Research 135 (2015)). Cumulative incidence of VTE (95% confidence intervals [CI]) at 12 months was calculated and stratified for KS risk group. Univariate and multivariate analysis identified associations between baseline variables and VTE within 12 months. Results: The study cohort included 15,388 cancer patients of whom 35% were female with a mean age 58.8 (SD 13.6) years, 85% had a solid tumor, and 46% received chemotherapy as the index anti-cancer therapy. Of these, 338 (2.2%) had a VTE within one year after cancer diagnosis (24% pulmonary embolism with or without deep vein thrombosis [DVT], 76% DVT). Table 1 shows baseline characteristics according to VTE status at 12 months. The 12-month cumulative incidence of VTE (95% CI) was 2.3% (2.1%-2.6%) overall, 1.6% (1.3%-1.8%) in the low-risk KS group and 5.6% (4.7%-6.4%) in the high-risk KS group, as shown in Figure 1. A multivariate model considered baseline variables shown in Table 1, as well as socioeconomic status, year of diagnosis, district and use of granulocyte colony stimulating factors. In this multivariate model, the following variables were associated with increased risk of VTE in the first year since index date: females, subjects living in the south of Israel, older age, increasing co-morbidity, and high KS. All non-chemotherapy anti-cancer treatments were associated with decreased VTE risk, compared to chemotherapy. Table 2 shows the hazard ratios with 95% CI. A total of 2896 patients (19%) initiated prophylactic AC after index date (LMWH/unfractionated heparin (UFH) in 2452 (85%)). Among patients with a VTE at any time post-index, 574 (90%) started AC within a median of 2 days (IQR: 0,7) after VTE diagnosis. AC used to treat cancer-associated VTE (defined as AC class 30-days post VTE diagnosis) included LMWH/UFH in 341(74%), direct oral anticoagulant in 74 (16%) and vitamin K antagonists in 43 (9%). Median time on AC after index VTE was 22.1 months (95% CI 17.2-38.4). Conclusion: This study confirms that the Khorana score identifies a population of cancer outpatients at higher risk of VTE, and that patients receiving chemotherapy are at highest risk. The association between VTE risk and geographical location in Israel suggests possible health care disparities. The majority of cancer patients with VTE received long term therapy with LMWH. Funding: This research was sponsored by Pfizer Conflict of Interest Statement: A. Leader is an employee of Rabin Medical Center who was paid as a consultant to Pfizer in connection with this study. O. Friedman-Mazursky &amp; M. Tirosh are employees of Pfizer Israel. The remaining authors declare no conflict of interest. Disclosures Friedman: Pfizer Pharmaceuticals Israel Ltd.: Current Employment. Tirosh:Pfizer Pharmaceuticals Israel Ltd.: Current Employment. Chodick:Novartis Pharma AG: Other: Institutional grant. Leader:Bayer Healthcare: Other: personal fees ; Pfizer Pharmaceuticals Israel Ltd.: Consultancy, Honoraria, Other: personal fees .

Venous Thromboembolism in Hospitalized COVID-19 Patients

Venous thromboembolism (VTE) is increasingly reported in seriously ill patients with COVID-19 infection. Incidence of VTE has been reported before and results varied widely in study cohorts. Incidence of major VTE (segmental pulmonary embolism and above and proximal deep vein thrombosis) which is a contributor to mortality and morbidity is not known. Also, data is unclear on the optimal anticoagulation regimen to prevent VTE. Multiple databases including PubMed were searched until May 12, 2020, to include studies reporting VTE in hospitalized COVID-19 adult patients. MOOSE guidelines were followed in selection, and 11 studies were included. We conducted a systematic review and meta-analysis to quantitatively assess the VTE burden in hospitalized COVID-19 patients and potential benefits of therapeutic dosing of anticoagulation compared with prophylaxis dosing for VTE prevention. Many societies and experts recommend routine prophylactic anticoagulation with heparin for VTE prevention in hospitalized COVID-19 patients. In this meta-analysis, the pooled rate of major VTE was 12.5% in hospitalized patients and 17.2% in intensive care unit patients. When therapeutic anticoagulation dosing was compared with prophylactic anticoagulation, the pooled odds ratio of VTE was 0.33 (95% confidence interval 0.14-0.75; P = 0.008, I = 0%) suggesting statistical significance with therapeutic dosing of anticoagulation for primary prevention of VTE in all hospitalized patients. However, this should be interpreted with caution as the bleeding events and safety profile could not be ascertained because of lack of adequate information. We recommend applying this finding to hospitalized COVID 19 patients only after carefully weighing individual bleeding risks and benefits. Major VTE events, especially pulmonary embolism, seem to be high in COVID-19 patients admitted to the intensive care unit. Therapeutic anticoagulation dosing seems to significantly benefit the odds of preventing any VTE when compared with prophylactic dosing in all hospitalized patients.

Venous Thromboembolism Chemoprophylaxis in Burn Patients: A Literature Review and Single-Institution Experience

Hospitalized burn patients meet the criteria for Virchow's triad (endothelial damage, hypercoagulability, and stasis), predisposing them to venous thromboembolism (VTE). Although the disease burden of VTE suggests a need for prevention in this population, unreliable reported VTE rates, costly and complicated prophylaxis regimens, and chemoprophylaxis risks have prevented the establishment of a universal protocol. This paper reviews thromboprophylaxis practices both in the literature and at our own institution. A systematic review was conducted according to PRISMA guidelines identifying studies pertaining to VTE chemoprophylaxis in burn patients. Additionally, medical records of patients admitted to an American Burn Association-verified burn center between June 2015 and June 2019 were retrospectively reviewed for demographics, chemoprophylaxis, and presence of VTE defined as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Thirty-eight studies met inclusion criteria. In the 12 studies that reported VTE incidence, rates ranged widely from 0.25% to 47.1%. The two largest retrospective studies (n = 33,637 and 36,638) reported a VTE incidence of 0.61% and 0.8% in populations with unknown or inconsistently recorded chemoprophylaxis. Throughout the literature, prevention protocols were mixed, though a trend toward using dose-adjusted subcutaneous low molecular weight heparin based on serum anti-factor Xa level was noted. At our burn center, 1,068 patients met study criteria. At-risk patients received a simple chemoprophylaxis regimen of 5000U of subcutaneous unfractionated heparin every 8 hours. No routine monitoring tests were performed to limit cost. Nine cases of DVT and two cases of PE were identified with an incidence of 0.84% and 0.19%, respectively, and a total VTE incidence of 1.03%. Only one patient developed heparin-induced thrombocytopenia (HIT). No cases of other heparin-associated complications were observed. VTE incidence rates reported in the literature are wide-ranging and poorly capture the effect of any one chemoprophylaxis regimen in the burn population. Our center uses a single, safe, and cost-effective protocol effecting a low VTE rate comparable to that of large national retrospective studies.

Incidence of deep vein thrombosis among non‐ICU patients hospitalized for COVID‐19 despite pharmacological thromboprophylaxis

BackgroundA remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID‐19 assisted in the intensive care unit (ICU). However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown. ObjectivesTo determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis. MethodsWe performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independent of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. ResultsThe population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6. Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98‐18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87‐5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23‐5.77). Significant differences between subjects with and without DVT were D‐dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P < .01). ConclusionsDVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.

Global epidemiology of venous thromboembolism in people with active tuberculosis: a systematic review and meta-analysis.

Despite the wide range of studies supporting an association between exposure to active tuberculosis and risk of venous thromboembolism (VTE), the current systematic review and meta-analysis is the first study assessing the global epidemiology of VTE in patients having active tuberculosis. In this systematic review and meta-analysis, EMBASE, Medline, and Web of Science were searched to identify observational studies, published until December 15, 2019, and reporting on venous thromboembolism in patients with active tuberculosis. No language restriction was applied. Studies were synthetized using a random-effect model. This review is registered with PROSPERO, CRD42019130347. We included 9 studies with an overall total of 16,190 patients with active tuberculosis. The prevalence of VTE was 3.5% (95% CI 2.2-5.2) in patients with active tuberculosis. Furthermore, we found a prevalence of pulmonary embolism (PE) at 5.8% (95% CI 2.2-10.7) and for deep vein thrombosis (DVT) at 1.3% (95% CI 0.8-2.0) in patients with active tuberculosis. Patients with active tuberculosis had a higher risk for VTE (OR 2.90; 95% CI 2.30-3.67), DVT (OR 1.56; 95% CI 1.14-2.14), and PE (OR 3.58; 95% CI 2.54-5.05). This study suggests that VTE is not rare among patients with active TB. Cost-effective preventive strategies and interventions to curb this dreadful burden of VTE among people with active TB are needed.