Development Of Venous Thromboembolism In Patients Research Articles

Non-O Blood Group and Pretreatment Risk of Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive non-Hodgkin lymphoma (NHL). It has been extensively documented that the risk of venous thromboembolism (VTE) is augmented in patients with aggressive lymphomas. The timing of VTE occurrence in this group of patients is highly variable and depends on diverse risk factors. Lately, it has been observed that ABO blood group type can have a prognostic impact on both thrombosis development and survival outcomes in patients with cancer. Therefore, the study aimed to examine the ABO blood group as a risk factor for VTE development in patients with DLBCL, to examine the relation between ABO blood groups and the timing of VTE development, and to investigate the association between ABO group type and treatment and survival outcomes. Methods: A total of 340 patients with DLBCL (newly diagnosed and relapsed) have been included in the study and all of them have been treated at the Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia. Data regarding VTE events were collected for all the patients included in the study, from the time of diagnosis to 3 months after the last cycle of therapy. ABO blood group has been determined before the treatment initialization. VTE was diagnosed objectively based on clinical examination, laboratory evaluation, and radiographic studies. Results: The median patients' age was 60 years (range, 19-89 years) and 52.9% were males. Newly diagnosed patients were dominant in the study population (94.4%). The majority of patients had advanced stage (stage III Ann Arbor 22.3% and stage IV 30.7%, respectively) of the disease. The median international prognostic index (IPI) was 2 (range, 0-5). Complete remission (CR) and partial remission (PR) were most commonly recorded (51.7% and 28.8%, respectively). The rate of VTE was 12.6% (43 patients), with the highest frequency of lower and upper extremity deep vein thrombosis (12 patients each). VTE was diagnosed before the initiation of specific hematological treatment in 54.5% of DLBCL patients, whilst 45.5% of DLBCL patients have been diagnosed with VTE following the hematological treatment initiation. The following distribution of ABO blood groups among DLBCL patients was detected: A blood group 39.4%, B blood group 17.6%, AB blood group 9.1%, and O blood group 33.8%. No significant association between VTE development and ABO group type was found (p=0.706) nor between VTE development and time of VTE development (p=0.895). The rate of VTE in DLBCL patients with A blood type was 4.7%, in B 2.1%, in AB 1.8%, and in O 4.1%, respectively (p=0.706). DLBCL patients with the non-O blood group developed VTE significantly more frequently prior to the hematological treatment commencement than after the treatment initiation (6.2% vs. 2.6%, p=0.003). Univariate logistic regression analysis showed that non-O blood type in DLBCL patients is a prognostic factor for VTE development prior to hematological treatment initiation (odds ratio (OR)=8.56, 95% confidence interval (CI): 1.92-38.21, p=0.005). Multivariate logistic regression model demonstrated that non-O blood type is an independent predictor of pretreatment VTE development in DLBCL patients (OR=18.33, 95% CI: 1.51-222.87, p=0.022). Therapy response of DLBCL patients was significantly associated with the ABO blood group (p=0.012) in the way that A and AB blood types were associated with unsatisfactory treatment response (no statistically significant association was found between ABO blood type and DLBCL patients' Ann Arbor stage, mediastinal involvement, bulky disease, extranodal disease, IPI, central nervous system involvement). Univariate regression analysis showed that A blood type is a predictor of unsatisfactory therapy response in patients with DLBCL (OR=1.85, 95% CI: 1.04-3.29, p=0.035). However, in multivariate regression model, this finding lost statistical significance. No significant association was observed regarding ABO blood type, progression-free survival, and overall survival in patients with DLBCL (p=0.398 and p=0.593, respectively). Conclusion: In DLBCL patients, non-O blood group is an independent predictor of VTE occurrence prior to initiation of a specific hematologic treatment. DLBCL patients with A blood group could be at risk of insufficient treatment response.

Thromboembolism risk in patients diagnosed with EGFR- and ALK-mutant lung adenocarcinoma

In this study, we investigated the incidence of venous thromboembolism (VTE), related risk factors for VTE, and the effect of VTE on overall survival in patients with non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations. The study included patients older than 18 years of age who were diagnosed with histologically proven locally advanced or advanced-stage adenocarcinoma and were followed in our center between January 2014 and December 2019. These patients were divided into two groups: one comprising mutation-positive individuals and the other mutation-negative individuals. We examined factors influencing the occurrence of VTE, assessed the incidence of VTE, and compared the differences in overall survival. Univariate Cox regression analysis revealed that the independent predictors of VTE were the number of metastases (Hazard ratio [HR]: 3.784; 95% confidence interval [CI]: 2.198 – 6.515; P < 0.001) and the presence of EGFR exon 21 mutations (HR: 2.386; 95% CI: 1.276 – 4.462; P = 0.006). However, in multivariate analysis, only the number of comorbidities was associated with an increased risk for VTE (HR: 3.462; 95% CI: 1.977 – 6.060; P < 0.001). It is essential to consider the risk of VTE development in patients with EGFR exon 21 mutation-positive lung adenocarcinoma. Physicians should be vigilant in terms of screening, prophylaxis, and follow-up for underlying VTE in these patients.

Factors Associated with Venous Thromboembolism Development in Patients with Traumatic Brain Injury.

Venous thromboembolic (VTE) events are a major concern in trauma and intensive care, with the prothrombotic state caused by traumatic brain injury (TBI) increasing the risk in affected patients. We sought to identify critical demographic and clinical variables and determine their influence on subsequent VTE development in patients with TBI. This was a cross-sectional study with data retrospectively collected from 818 patients with TBI admitted to a level I trauma center in 2015-2020 and placed on VTE prophylaxis. The overall VTE incidence was 9.1% (7.6% deep vein thrombosis, 3.2% pulmonary embolism, 1.7% both). The median time to diagnosis was 7days (interquartile range 4-11) for deep vein thrombosis and 5days (interquartile range 3-12) for pulmonary embolism. Compared with those who did not develop VTE, patients who developed VTE were younger (44 vs. 54years, p = 0.02), had more severe injury (Glasgow Coma Scale 7.5 vs. 14, p = 0.002, Injury Severity Score 27 vs. 21, p < 0.001), were more likely to have experienced polytrauma (55.4% vs. 34.0%, p < 0.001), more often required neurosurgical intervention (45.9% vs. 30.5%, p = 0.007), more frequently missed ≥ 1 dose of VTE prophylaxis (39.2% vs. 28.4%, p = 0.04), and were more likely to have had a history of VTE (14.9% vs. 6.5%, p = 0.008). Univariate analysis demonstratedthat 4-6 total missed doses predicted the highest VTE risk (odds ratio 4.08, 95% confidence interval 1.53-10.86, p = 0.005). Our study highlights patient-specific factors that are associated with VTE development in a cohort of patients with TBI. Although many of these are unmodifiable patient characteristics, a threshold of four missed doses of chemoprophylaxis may be particularly important in this critical patient population because it can be controlled by the care team. Development of intrainstitutional protocols and tools within the electronic medical record to avoid missed doses, particularly among patients who require operative interventions, may result in decreasing the likelihood of future VTE formation.

ABO BLOOD GROUP TYPE AND RISK OF VENOUS THROMBOEMBOLISM IN PATIENTS WITH LYMPHOMA

Introduction: Risk of venous thromboembolism (VTE) is increased in patients with cancer owing to various pathophysiological mechanisms that generate prothrombotic state. Lymphoma patients are well known to be at significant risk for VTE development. Recently, non-O blood type was associated with increased risk of VTE in patients with cancer and it has been proposed as time-dependent predictor of VTE in that group of patients. The aim of the study was to examine ABO blood group as a risk factor for VTE development in patients with lymphoma. Methods: A total of 600 patients with lymphoma (newly diagnosed and relapsed) have been included in the study. All the patients have been treated at Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia. Data regarding VTE events was collected for all the patients included in the study, from the time of diagnosis to 3 months after the last cycle of therapy. ABO blood group has been determined prior to treatment initialization through standard institutional procedure. VTE was diagnosed objectively based on radiographic studies, clinical examination, and laboratory evaluation. Results: The median patients' age was 57 years (range 18–89 years); 55.5% were males. The majority of the patients were newly diagnosed (88.8%). The distribution of the diagnosis was following: indolent NHL 140 (23.3%), aggressive NHL 366 (61%), and Hodgkin lymphoma 94 (15.7%), respectively. The rate of VTE was 10.3% (62 patients), with the highest rate in aggressive NHL group of patients (7.7%, 46 patients). VTE was diagnosed before the specific hematological treatment initiation in 46.8% of lymphoma patients, whilst 53.2% of lymphoma patients have been diagnosed with VTE after the hematological treatment commencement. A blood type was the most common in our group of patients (41.6%), followed by O blood type (33.3%), B blood type (15.8%) and AB blood type (9.3%), respectively. There was no statistically significant association between VTE development and ABO group type (p = 0.495). Non-O blood type lymphoma patients with VTE had significantly more often developed VTE prior to the treatment initiation in comparison with O blood type lymphoma patients with VTE (2.5% vs. 1%, p = 0.04), whereas VTE in O blood type lymphoma patients was significantly more often after the initiation of hematological treatment in comparison with VTE in non-O blood type patients (3.8% vs. 3%, p = 0.04). Logistic regression model demonstrated that non-O blood type is a predictor of pre-treatment VTE development in lymphoma patients (odds ratio [OR] = 3.19, confidence interval [CI]: 1.03–9.88, p = 0.044). Conclusions: While there is no association between frequency of ABO blood group and the rate of VTE in lymphoma patients, non-O blood type in lymphoma patients has shown to be a predictor of VTE development prior to specific hematologic treatment commencement. Encore Abstract—previously submitted to EHA 2023 Keywords: diagnostic and prognostic biomarkers, Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.

Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas

IntroductionPodoplanin (PDPN) is known to induce platelet aggregation via interacting with the C-type lectin-like receptor-2 on platelets and is involved in postoperative venous thromboembolism (VTE) formation. In this study, we investigate the correlation between soluble C-type lectin-like receptor (sCLEC-2) levels and PDPN expression in patients with high grade gliomas and the relationship between sCLEC-2 levels and the occurrence of VTE. Materials and methodsForty-four patients harboring high grade gliomas, treated surgically at the Department of Neurosurgery, Niigata University from April 2018 to August 2020, were included. Patients with high grade gliomas were divided into isocitrate dehydrogenase (IDH)- wildtype and mutant groups, and the presence or absence of VTE and the intensity of PDPN by immunohistochemistry were confirmed. Platelet counts, as well as plasma sCLEC-2 and PDPN were measured in these patients. Furthermore, the levels of sCLEC-2 concentration were divided by the platelet count (C2PAC index) for comparison. ResultsIDH-wildtype glioma patients highly expressed PDPN (P < 0.001) compared to IDH-mutant glioma patients. In total, 9 (20.5 %) patients were diagnosed with VTE during the follow-up period, of which 8 patients harbored IDH-wildtype gliomas, and one patient an IDH-mutant glioma. Mean sCLEC-2 levels and C2PAC index in patients with IDH-wildtype gliomas were significantly higher than that of low or no PDPN expression group, which included patients with IDH-mutant gliomas (P = 0.0004, P = 0.0002). In patients with IDH-wildtype gliomas, the C2PAC index in patients with VTE was significantly higher than in patients without VTE (P = 0.0492). The optimal cutoff point of C2PAC for predicting VTE in IDH-wildtype glioma patients was 3.7 with a sensitivity of 87.5 % and specificity of 51.9 %. ConclusionPlatelet activation is strongly involved in the development of VTE in patients with IDH-wildtype high grade gliomas, and C2PAC index is a potential marker to detect VTE formation after surgery.

Immune activation and inflammatory biomarkers as predictors of venous thromboembolism in lymphoma patients

BackgroundLymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma.MethodsThe erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE.ResultsThe majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE.ConclusionInflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.

Does carbapenem-resistant enterobacteriaceae infection drive venous thromboembolism in patients admitted to intensive care units receiving prophylactic anticoagulants?

BACKGROUND: Systemic infections are one of several risk factors leading to the development of inflammation and venous thromboembolism (VTE) formation. This study aimed to assess the risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU).MATERIALS AND METHODS: A retrospective-matched case − control study of patients with VTE in the period between January 1, 2018, and December 31, 2019. We included all adult patients who stayed more than 2 days in ICU before the development of VTE.RESULTS: Univariate and multivariate analyses uncovered three of six factors to have significant influence in the development of VTE in ICU patients: Carbapenem-resistant Enterobactereaceae (CRE) infections (odds ratio [OR] 2.95, 95% confidence interval (CI) 1.21–7.33, P = 0.010), length of ICU stay (OR 1.02, 95% CI 1.01–1.04, P = 0.011), and the sequential organ failure assessment score (OR 1.10, 95% CI 1.01–1.20, P = 0.031); all were found to be independent risk factors in the development of VTE.CONCLUSION: Our findings suggest that, CRE infection is a strong trigger to the development of VTE in patients admitted to the ICU, and draw the attention of the treating clinicians to prioritize these infections in the management protocols to control infection-driven VTE in ICU patients.

Rate of Development of Venous Thromboembolism in Lateral Skull Base Surgery.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality for surgical patients. This article aims to determine factors that may have contributed to the development of VTE in patients undergoing lateral skull base surgery, to assess the validity of the Caprini Risk Assessment Model (RAM) score in this subset of patients, and to determine the efficacy of mechanical DVT prophylaxis alone in preventing VTE. Retrospective chart review. A retrospective chart review was conducted of patients who underwent skull base surgery for vestibular schwannoma, and the rate of VTE was assessed. Patient demographics, comorbidities, and treatment factors were examined to determine risk factors associated with the development of a postoperative thrombotic event. Caprini RAM scores were compared for patients who developed a VTE. Among 197 patients, the rate of VTE formation was 3.5%. No individual risk factor independently contributed to the development of a thrombotic event. The mean Caprini RAM score was 4.06 in patients who did not develop a VTE and 5.14 in the patients that did develop a VTE (P=.005). The Caprini score was significant for the risk of VTE formation, with an odds ratio of 2.8 (P=.009, 95% CI=1.3-6.2). Venous thromboembolism rates are relatively low following lateral skull base surgery. While there is no individual risk factor associated with increased VTE risk, the Caprini RAM score appears to be a useful predictor of risk. The Caprini score may be useful in identifying high-risk patients who may benefit from chemoprophylaxis for VTE prevention. 3 Laryngoscope, 132:662-667, 2022.

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.

Contrasts in Glioblastoma-Venous Thromboembolism versus Bleeding Risk.

Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.

D-Dimer Improves Risk Prediction of Venous Thromboembolism in Patients with Multiple Myeloma

Introduction: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations. Recently, a clinical prediction model was developed to identify patients with newly diagnosed MM starting chemotherapy at highest risk of VTE. The model, IMPEDE VTE, found the following clinical risk factors for VTE: immunomodulatory drugs, body mass index, recent pathologic fracture of the femur or hip, erythropoietin stimulating drugs, dexamethasone, doxorubicin, Asian ethnicity/race, history of VTE, tunneled line or central venous catheter, and existing use of aspirin or anticoagulation. External validation of the model has yielded a c-statistic for VTE risk prediction of 0.64 to 0.65. Laboratory parameters can predict VTE in some patients with cancer. Accordingly so, the addition of laboratory parameters to IMPEDE VTE has the ability to improve model performance. Thus, we sought to determine the association between soluble P-selectin and D-dimer with the development of VTE in patients with newly diagnosed MM starting chemotherapy. Methods: We identified 545 patients from the Washington University in St. Louis MM banking protocol, with available plasma from time of diagnosis (2007-2019). Thirty-eight cases of VTE were identified within 6 months following treatment initiation. An additional 137 patients were randomly selected as controls. D-dimer and soluble P-selectin ELISA assays were performed on the banked plasma by Eve Technologies, who was blinded to case vs. control status. Both assays were performed in duplicate and results averaged. All additional variables were collected through manual chart abstraction. IMPEDE VTE scores were calculated as we previously described (Sanfilippo et al.). The association of D-dimer and soluble P-selectin with VTE risk was assessed using Cox regression, adjusting for IMPEDE VTE score. Results: The median age of all 545 patients was 65 (range 32-79), 54% were male, and 85% were white. All patients received novel chemotherapy agents for first-line MM therapy and 66% underwent autologous stem cell transplant. Of the 38 cases with VTE, 20 patients had deep vein thrombosis, 17 had pulmonary emboli, and 1 patient had concurrent events. The median time from chemotherapy initiation to VTE was 51 days (range 4-193). The median IMPEDE VTE score was 5 (range -1 to 12). Each unit increase in IMPEDE VTE score was associated with a 21% increase in risk for VTE (HR 1.21; 95% CI 1.04-1.40; p = 0.01). Median D-dimer was 11,795 ng/mL (range 280-144,832). Each 1000 ng/mL unit increase in D-dimer was associated with a 2% increase risk for VTE after controlling for IMPEDE VTE score (aHR 1.02; 95% CI 1.01-1.04; p &amp;lt; 0.001). Patients in the highest quartile of D-dimer levels, above the 75th percentile, had a 2-fold increase in risk of VTE after adjusting for IMPEDE VTE score (aHR 2.04; 95% CI 1.03-4.02; p = 0.04). Median soluble P-selectin was 189 ng/ml (range 23-638). There was no association between soluble P-selectin level and VTE risk in patients with MM. Conclusions and Relevance: D-dimer is predictive of VTE in patients with MM starting chemotherapy. The combination of D-dimer and the IMPEDE VTE score can improve identification of patients at high risk of VTE and therefore allow for selection of primary thromboprophylaxis among patients with MM. Disclosures Sanfilippo: Bayer HealthCare Pharamceuticals: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Other: Travel Support for Investigator Meeting; Pfizer: Membership on an entity's Board of Directors or advisory committees; Covington &amp; Burling LLP: Consultancy; Luther &amp; Associates: Consultancy; Health Services Advisory Group: Consultancy; Amgen: Other: Trasfer of Value (food) during discussion of research.

Assessing the risk of venous thromboembolism in multiple myeloma

Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE) compared to the general population. This risk is highest during the first year of diagnosis and subsequently decreases over time. Development of VTE in patients with MM is associated with inferior outcomes, with patients with VTE and MM having an increased risk of death compared to those with MM without VTE. Primary thromboprophylaxis has the potential to decrease risk of VTEksanfilippo@wustl.edu (K.M. Sanfilippo) in MM and improve outcomes. Current studies assessing thromboprophylaxis in MM excluded patients at high risk of VTE. A meta-analysis of trials of primary thromboprophylaxis in ambulatory cancer patients at high risk of VTE identified by use of a risk-prediction score found a reduction in risk of VTE with prophylaxis with no significant increase in risk of major bleeding. However, these trials contained relatively few patients with MM. Three clinical risk prediction scores are available to assess risk of VTE in MM: 1) the International Myeloma Working Group (IMWG)/National Comprehensive Cancer Network (NCCN); 2) the SAVED score; and 3) the IMPEDE VTE score. The latter two have recently been shown to outperform the IMWG/ NCCN score for predicting VTE in MM. Biomarkers have the potential to improve prediction of VTE in patients with MM. Future research should focus on the addition of biomarkers to available risk scores in MM to improve discrimination in this high-risk patient population.

Incidence, Therapy, and Bleeding Risk-Cancer- Associated Thrombosis in Patients with Glioblastoma.

Cancer is an independent risk factor for the development of venous thromboembolism (VTE). Glioblastomas are amongst cancer types with the most thrombogenic potential and patients are at a particularly high risk of VTE with an incidence up to 20–30% per year. Currently, major efforts are underway to gain novel insights into risk factors and pathomechanisms to provide a better understanding of development of VTE in patients with primary brain tumors. Treatment of VTE requires therapeutic anticoagulation, which accordingly to recently-published guidelines should be performed using low molecular weight heparin or, in case of low bleeding risk, using a direct oral anticoagulant. However, this can be very challenging due to an increased risk of intracranial hemorrhage in this patient group. Furthermore, limited data are available on the subgroup of patients with primary brain tumors.

Increased Health Care Cost Associated with Venous Thromboembolism in Patients with Malignant Glioma

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. In patients with MG and VTE the chance of two-year survival is significantly reduced. The development of VTE is also associated with increased morbidity, including increased risk of hospitalization, delays in cancer treatment, and an increased risk of complications including pain, bleeding, and bruising from high dose therapeutic anticoagulation. The economic burden of VTE in cancer patients is estimated at a 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 patients with MG.Methods: A retrospective chart review of patients with MG at an academic medical center was conducted from 2009-2017. Sixty-seven patients, age 18 years and older, with a histologic diagnosis of MG (WHO grade III-IV) were assessed. The number of office visits, emergency room visits, and inpatient hospitalizations with the associated costs of VTE management and its 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 67 patients in the study, 18 developed VTE (27%). All patients who developed a VTE were placed on therapeutic anticoagulation. Fifty percent of patients developed complications related to anticoagulation, including gastrointestinal, retroperitoneal and intracranial bleeding events. Two patients required placement of an IVC filter after experiencing a bleeding complication. Patients that developed VTE had an increase in inpatient days (16.6 inpatient days) as compared to their non-VTE counterparts (8.8 inpatient days), (p=0.012). There was increased utilization of the emergency room with an average of 3.94 visits in those patients with VTE as compared to those without (1.84), (p=0.003). A full cost analysis found that the average primary total cost for ED visits and inpatient hospitalizations in patients with VTE was $48,863 while those without VTE averaged $35,948. This represented a 26% increase in the average primary total cost in those patients with VTE.Discussion: The development of VTE in patients with MG increases inpatient admissions days and incurs additional pharmaceutical costs related to anticoagulation. This study represents the first assessment of VTE-associated health care burden specific to primary brain cancer. We confirm that VTE affects a large number of patients with MG (27%) and limits the time spent at home due to increased hospitalizations and emergency room visits. VTE may be a preventable complication and further studies are needed to investigate safe prevention strategies for patients with MG. DisclosuresNo relevant conflicts of interest to declare.

Platelet (hem)ITAM Signaling Mediated Cancer-Associated Venous Thrombosis

Background-Patients with cancer are at a high risk of venous thromboembolism (VTE) and underlying mechanisms are unclear. Recent studies have shown that podoplanin (PDPN) expressing highly in primary brain tumors is associated with increasingly risk of VTE by activate platelets. The C-type lectin-like receptor 2(CLEC-2) is a type II transmembrane protein expressed on the surface of platelets and PDPN is the only known endogenous ligand for it. CLEC-2 mediates platelet activation through a hem-immunoreceptor tyrosine-based activation motif ((hem)ITAM).Objective: We tested the hypothesis that the platelet (hem)ITAM signaling is involved in the development of VTE in patients with malignant tumors, and targeted inhibitors may reduce thrombosis and improve prognosis in patients with cancer.Materials and Methods-We selected two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN as models to study the role of the platelet (hem)ITAM signaling in cancer-associated venous thrombosis in vitro and in vivo.Results and Conclusions-Our results showed that both types of cell lines expressing PDPN triggered platelet activation via CLEC-2 in vitro, which could be abrogated by an anti-PDPN antibody SZ-168 or syk inhibitor R406. Further, in vivo study showed that injection of NCI-H226 or C8161 in two mouse models of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. These results suggested that platelet activation induced by PDPN was correlated with hypercoagulability, contributed to thrombosis in cancer patients. Importantly, PDPN enhanced thrombosis was reduced in mice treated with SZ168 or R406. Immunohistochemical staining using anti-PDPN antibody was also performed in pulmonary squamous cell carcinoma specimens of 166 patients. During up to 4-year-follow-up, 20 (12.05%) patients developed VTE. 105 tumor specimens stained positive for PDPN (27 high expression, 43 medium expression, 35 low expression). High PDPN expression was associated with an increased risk of VTE and poor prognosis, independently of age, sex and tumor type. In this study, we found that PDPN expression in tumors induced platelet aggregation and was associated with a high risk of VTE via platelet (hem)ITAM signaling. Our data also suggested that SZ168 inhibited PDPN-induced platelet aggregation in vitro and decreased the incidence of VTE in mice. In conclusion, our research demonstrated novel insights into the pathogenesis of cancer-associated venous thrombosis. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of risk factors and assessment models for predicting venous thromboembolism in lung cancer patients

The aim of the study was to investigate the prognostic significance of selected risk assessment models (RAMs) for predicting venous thromboembolism (VTE) events in patients undergoing outpatient chemotherapy for lung cancer. We evaluated the following VTE-risk assessment tools: Khorana risk score (KRS), PROTECHT score, CONKO score and COMPASS-cancer-associated thrombosis score (COMPASS-CAT). Retrospective analyses were performed on 118 patients with lung cancer, 20 of whom developed VTE with a median of 2.5 months from diagnosis. Patients receiving gemcitabine-based regimen (25%), patients with a history of atrial fibrillation (AF) and patients with chronic kidney disease developed VTE more often than other patients. In the multivariate analysis, high COMPASS-CAT score (OR 8.73; 95% CI 1.01–75.22, P = 0.049), gemcitabine chemotherapy (OR 3.37; 95% CI 1.09–10.39, P = 0.035) and AF (OR 7.19; 95% CI 1.89–27.33, P = 0.004) were all significantly associated with VTE development. VTE occurred in; 13% (n = 2) of the KRS high-risk group, 17.7% (n = 11) of the PROTECHT high-risk group, 15% (n = 4) of the CONKO high-risk group and 23.8% (n = 20) of the COMPASS-CAT high-risk group (n = 84). Only the COMPASS-CAT score was able to identify 100% of patients who developed VTE, and best discriminated between patients with high and low risk of VTE development (C statistic 0.89). The ROC analysis indicated a cutoff value of 11 points (95% CI 0.821–0.962) for COMPASS-CAT for VTE development in patients with lung cancer. In conclusion, in our study of all the VTE–RAMs analyzed, the COMPASS-CAT model was the most accurate predictor of VTE development in patients with lung cancer.

Risk profile, management, and outcomes of patients with venous thromboembolism attended in Spanish Emergency Departments: The ESPHERIA registry.

The objective of this study was to determine the clinical profile of and diagnostic and therapeutic approach to patients with venous thromboembolism (VTE) in Spanish Emergency Departments (EDs). Risk factors, adherence to clinical practice guidelines, and outcomes were also evaluated.Patients with VTE diagnosed in 53 Spanish EDs were prospectively and consecutively included. Demographic data, comorbidities, risk factors for VTE, index event characteristics, hemorrhagic risk, and mortality were evaluated. Adherence to clinical practice guidelines was assessed based on clinical probability scales, requests for determination of D-dimer, use of anticoagulant treatment before confirmation of diagnosis, and assessment of bleeding and prognostic risk. Recurrence, bleeding, and death during admission and at 30, 90, and 180 days after diagnosis in the EDs were recorded.From 549,840 ED visits made over a mean period of 40 days, 905 patients were diagnosed with VTE (incidence 1.6 diagnoses per 1000 visits). The final analysis included 801 patients, of whom 49.8% had pulmonary embolism. The most frequent risk factors for VTE were age (≥70 years), obesity, and new immobility. Clinical probability, prognosis, and bleeding risk scales were recorded in only 7.6%, 7.5%, and 1% of cases, respectively. D-dimer was determined in 87.2% of patients with a high clinical probability of VTE, and treatment was initiated before confirmation in only 35.9% of these patients. In patients with pulmonary embolism, 31.3% had a low risk of VTE. Overall, 98.7% of patients with pulmonary embolism and 50.2% of patients with deep venous thrombosis were admitted. During follow-up, total bleeding was more frequent than recurrences: the rates of any bleeding event were 4.4%, 3.9%, 5.3%, and 3.5% at admission and at 30 and 90, and 180 days, respectively; the rates of VTE recurrence were 2.3%, 1.3%, 1.7%, and 0.6%, respectively. Mortality rates were 3.4%, 3.1%, 4.1%, and 2.6% during hospitalization and at 30, 90, and 180 days, respectively.VTE had a substantial impact on Spanish EDs. The clinical presentation and risk profile for the development of VTE in patients diagnosed in the EDs was similar to that recorded in previous studies. During follow-up, bleeding (overall) was more frequent than recurrences. Adherence to clinical practice guidelines could improve significantly.

Association between Level of Tumor Markers and Development of VTE in Patients with Pancreatic, Colorectal and Ovarian Ca: Retrospective Case- Control Study in Two Community Hospitals.

The risk of venous thromboembolism (VTE) is increased in patients with cancer. However, the role of tumor markers as potential indicators of increased risk of VTE is still undetermined. In this retrospective observational case control study, levels of the tumor markers CEA, CA 19-9 and CA 125 in patients with colorectal, pancreatic, and ovarian cancer respectively, who were admitted to two community hospitals between January 2001 and December 2011, were compared between patients who were VTE positive and those who were VTE negative. The primary goal of this study was to determine whether VTE positive cancer patients had higher tumor marker levels compared to VTE negative cancer patients. In our study, 66.7% (48/72) of patients who were positive for VTE had elevated tumor markers while 65.3% (66/101) of patients who were negative for VTE had low (normal) tumor markers, indicating an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of <0.0001 (95% CI of 1.99-7.14). When the VTE group was further divided into DVT and PE groups, 70.2% (40/57) of patients in the DVT positive group had high tumor markers with a p value of <0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89) while 57.9% (11/19) of patients in pulmonary embolism positive group had high tumor markers; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). In this retrospective study of 173 individuals with a diagnosis of either colorectal, pancreatic, or ovarian Cancer, higher tumor marker levels (CEA, CA 19-9, and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant only for DVT but not for PE.

Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis.

Venous thromboembolism (VTE) is a common complication after surgical treatment of fractures, which is associated with significant morbidity and mortality. Identifying the risk factors for VTE is important for preventive strategies to reduce the incidence of VTE. Therefore, we conducted a meta-analysis to evaluate the incidence of VTE and the risk factors influencing the development of VTE in patients who underwent surgery for fractures below the hip. PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China) and CNKI (National Knowledge Infrastructure, China) databases were systematically searched to identify cohort or case-control studies that investigated the incidence and risk factors for VTE following surgical treatment of fractures below the hip. VTE risk ratios (RRs) were pooled by use of a fixed-effect model or a random-effect model, depending on the heterogeneity among the included studies. Heterogeneity between the studies was assessed by I2 statistics. Twenty-three studies with a total of 191 294 patients who met the inclusion criteria were included in this meta-analysis. Our results demonstrated that age (≥60 years) (RR = 1·85, 95% confidence interval (CI): 1·34, 2·55; P = 0·000), previous VTE(RR = 5·25, 95% CI: 2·77, 9·96; P = 0·000), heart failure (RR = 1·74, 95% CI: 1·34, 2·27; P = 0·000), current smoking status (RR = 1·23, 95% CI: 1·07, 1·41; P = 0·004), hypertension (RR = 1·62, 95% CI: 1·27, 2·06; P = 0·000), hyperlipidaemia (RR = 2·16, 95% CI: 1·79, 2·62; P = 0·000), diabetes mellitus (RR = 1·46, 95% CI: 1·27, 1·68; P = 0·000), obesity (RR = 1·58, 95% CI: 1·35,·1·85; P = 0·000), multiple fractures (RR = 2·14, 95% CI: 1·00, 4·60; P = 0·050), varicose veins (RR = 3·07, 95% CI: 1·12, 8·47; P = 0·030), prolonged operation time (weighted mean differences (WMD) = 1·22, 95% CI: 0·63, 1·81; P = 0·000) and prolonged bed rest time (WMD = 3·12, 95% CI: 2·96, 3·29; P = 0·000) were associated with an increased risk of developing VTE. The other variables, including age (<60 years), previous smoking, immobility, pregnancy, cancer, open fractures and combination with trauma were not identified as significant risk factors for VTE. Almost all the risk factors mentioned above are in line with the known risk factors for VTE following surgery for fractures below the hip. Thus, surgeons should pay close attention to patients with these medical conditions in order to reduce the incidence of VTE following surgical treatment of fractures below the hip.

Coronary endothelial dysfunction is associated with increased risk of venous thromboembolism

BackgroundNormal endothelial function is central to physiologic anticoagulation mechanisms. Endothelial dysfunction may predispose to venous thromboembolism (VTE). We aimed to investigate if coronary endothelial dysfunction (CED) predicts development of VTE in patients presenting with coronary atherosclerosis without critical stenoses. MethodsCoronary microvascular function was evaluated in 502 patients with coronary atherosclerosis without critical stenoses by administration of intracoronary acetylcholine at the time of diagnostic study. After a median follow-up of 6.3years, patients were assessed for the development of VTE by administration of a questionnaire.Coronary microvascular endothelial dysfunction was defined as ≤50% increase in coronary blood flow from baseline in response to maximal dose of acetylcholine. ResultsThe median age was 53years (IQR: 45, 62) 68% were female and CED occurred in 279 (56%) patients. Hypertension (40.8%), diabetes (8.4%), and hyperlipidemia (58.3%) were common risk factors. There were no differences in baseline characteristics between those with and without CED. There were 9 VTE events (6 unprovoked) among patients with CED compared to no events in the control group (P=0.01). DiscussionCED was associated with the development of VTE. Endothelial injury by causing disruption of vascular hemostasis may play a role in predisposing patients to VTE.