Onset Of Venous Thromboembolism Research Articles

Risk of venous thromboembolism in relation to high physical activity level in men over 27 year follow up.

Venous thromboembolism (VTE) is the third most common type of cardiovascular disease. An association between high level of physical activity (PA) and the onset of VTE has been found in some, but not all previous studies. We aim to study the association between PA-level and VTE in a cohort of men with updated data on PA levels at four occasions. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM) study initiated in 1970, a study of men at age 50 years (n = 2,294 at baseline) examined on leisure time PA by questionnaire and traditional cardiovascular risk factors. Examinations were repeated at ages 60, 70, and 77, and follow-up was completed after a median time of 33 years. Cox regression analysis with hazard ratios (HRs) using updated covariates for PA and risk factors was performed on the association of PA levels with incident VTE, with adjustments for established cardiovascular risk factors (systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking). Totally 186 men experienced a VTE during follow-up of 68,263 person-years at risk. Individuals with the highest PA level had an increased relative risk of VTE, adjusted HR, 2.22 (95% CI 1.05-4.67), when compared to individuals with the lowest level of PA. In this cohort of men with a follow-up of 27 years, the risk of VTE was increased at the highest PA level. Findings indicate that there could be an increased VTE risk with higher PA level including strenuous activities.

Design and validation of algorithms to identify venous thromboembolism in the French National Healthcare Database.

This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value. A case-identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra-database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de-identified pooled and formatted SNDS data (i.e., reconstituted electronic health records-rEHR) with a 6-month look-back period prior to the supposed VTE onset and a 12-month follow-up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert-confirmed VTE divided by the number of algorithm-identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE-identifying algorithm was updated based on expert recommendation. For the 150 patients identified with the first VTE-identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54-69]). The final VTE-identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86-98]) with a total of 87 algorithm-identified cases, including 80 retrieved from the 92 confirmed by experts. The identification of VTE in the SNDS is possible with a good PPV.

Incidence and Time Course of Symptomatic Thromboembolic Outcomes After Lower Extremity Arthroscopic Surgery, Ankle Fracture Surgery, and Achilles Tendon Repair.

The incidence and time course of acute venous thromboembolism (VTE) after ambulatory surgery for lower extremity orthopaedic conditions is not well-defined. The purpose of this study was to analyze the incidence, the time course, and risk factors associated with clinically diagnosed acute deep vein thrombosis or pulmonary embolism within 3 months of surgery in patients undergoing specific operations for lower extremity injuries. Patients undergoing arthroscopic procedures of the knee, ankle fracture surgery, Achilles tendon repair, and ankle arthroscopy from January 1, 2005, to December 31, 2010, were identified in the California Ambulatory Surgery database with linkage to hospital discharge data, emergency department data, and a death registry. Outcomes were acute VTE and death within 90 days. Time courses were compared using Kaplan-Meier analysis, and risk factors were analyzed using proportional hazard modeling. Analysis of data from 468,699 surgeries showed that the cumulative incidence of acute VTE was significantly higher after Achilles tendon repair (0.72%, P < 0.001) than ankle fracture surgery (0.33%), knee arthroscopy procedures (range, 0.29% to 0.41%), or ankle arthroscopy (0.24%). The time course of diagnosis of VTE was similar for all arthroscopic procedures (median postoperative day for diagnosis = 9 to 10; 80% by 22 to 36 days), whereas for Achilles tendon surgery, the time course was protracted (median postoperative day for diagnosis = 29 days; 80% by 51 days). Ninety-day mortality was low (<0.06%) after all procedures except ankle fracture (0.12%). Predictors of pulmonary embolism included age older than 60 years (HR, 3.1; 95% CI; 2.0 to 4.8, versus younger than 30 years), Achilles tendon repair (HR, 3.8; 95% CI; 2.8 to 5.3), and ankle fracture surgery (Hazard Ratio [HR], 2.1; 95% Confidence Interval [CI]; 1.5 to 2.8); Asian/Pacific Islander (HR, 0.3; 95% CI; 0.1 to 0.6) and Hispanic patients (HR, 0.5; 95% CI; 0.4 to 0.7) had significantly lower risk. The incidence and time course of onset of acute VTE after lower extremity orthopaedic surgeries varies significantly depending on the surgical procedure. These findings have implications regarding the use and duration of pharmacologic thromboprophylaxis.

Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry.

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear. Objectives This study aimed to validate the Khorana VTE risk assessment score (KRS) for VTE diagnosis and establish an optimal predictive model for VTE in Japanese patients with cancer. Methods A total of 7,955 Japanese patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups according to the KRS. Using 37 explanatory variables, a total of 2,833 patients with cancer were divided into derivation and validation cohorts (5:5). A risk model for Japanese participants was developed using the derivation cohort data. Results The prevalence of VTE in low-, intermediate-, and high-score patients was 1.2, 2.5, and 4.3%, respectively. Logistic regression analysis demonstrated that cancer stage (III-IV) and KRS ≥ 2 were independent and significant predictors of VTE onset. The risk model for VTE assigned 1 point to body mass index ≥25 kg/m 2 and 2 points each to the prevalence of osteochondral cancer and D-dimer level ≥1.47 µg/mL. The areas under the curve of the risk model were 0.763 and 0.656 in the derivation and validation cohorts, respectively. Conclusion The KRS was useful in Japanese patients, and our new predictive model may be helpful for the diagnosis of VTE in Japanese patients with cancer.

Cellular Components in Whole Blood Contribute to the Development of Thromboembolic Events in Patients with Pancreatic Cancer

Introduction Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC), causing morbidity and mortality. One in five patients with newly diagnosed PDAC develops a venous thromboembolism (VTE), which is associated with a decreased overall survival time . Patients with PDAC often have altered blood cell counts, which are further affected by systemic therapy. The high thromboembolic risk in patients with PDAC may be caused by pro-coagulant effects of pancreatic cancer on blood cells. Currently, there are no risk assessment tools or biomarkers available that can identify PDAC patients at highest risk of VTE. Aims To investigate the impact of PDAC on blood cell dependent coagulation, to characterize the high thrombosis risk in PDAC patients.To predict thromboembolic events in patients with PDAC using blood cell dependent assays, performed in whole blood. Methods Patients with locally advanced or metastatic PDAC (n=18) were included in a prospective, observational, case-control study (TROCOPAC study). At inclusion, before the initiation of chemotherapy, blood was collected to study whole blood (WB) coagulation profiles. Thrombin generation (TG) was measured in WB and platelet poor plasma (PPP) of 18 patients with PDAC and 18 healthy individuals matched for age and sex. The capacity of platelets to release granules was measured in a time-dependent manner upon stimulation with a PAR1 receptor agonist in WB. Patients were followed for 6 months upon inclusion. The primary endpoint was the onset of thromboembolic events, both VTE and arterial thromboembolism (ATE). Results Patients with PDAC have an increased endogenous thrombin potential (ETP) in whole blood. This difference was not observed in PPP, indicating a procoagulant effect caused by blood cells. Furthermore, patients with PDAC have a prolonged lag time in whole blood, while the lag time in PPP was not different between patients and controls. Platelet and white blood cell counts (WBC) significantly correlated with the WB ETP and peak in patients with PDAC, which was not observed in healthy controls. Of the 18 PDAC patients, 4 developed a VTE (22%) and 1 an ATE (6%). A shorter lag time of WB-TG and an increased maximum capacity of platelets to release granules, at study inclusion, were associated with incident thromboembolic events. Conclusions Patients with PDAC have an imbalanced WB-TG profile. The lag time in WB-TG and the granule release capacity of platelets predict an increased incidence of thromboembolic events. Red blood cell and white blood cell abnormalities in PDAC are associated with this disturbance in thrombin generation. Platelets and white blood cells hence appear to be a driving force in the development of thrombosis in patients with PDAC. As such, measuring hemostasis in whole blood would improve the thrombosis risk estimation in PDAC patients.

High Rates of Thrombotic Events in Newly Diagnosed Multiple Myeloma Patients Enrolled on the Maia Trial

Background. Patients with newly diagnosed multiple myeloma (NDMM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Despite the availability of the IMWG and NCCN VTE prophylaxis guidelines and updated risk stratification models such as SAVED and IMPEDE, the optimal thromboprophylaxis strategy is unknown, especially in the age of modern daratumumab-containing regimens. To continue highlighting the importance of appropriate thromboprophylaxis for patients with NDMM, we performed a post-hoc analysis of the randomized phase 3 MAIA trial to identify rates of venous and arterial thromboembolism. Methods. This retrospective study, carried out under YODA Project #2021-4663, used data from the randomized phase 3 MAIA trial that investigated lenalidomide and dexamethasone (Rd) with or without daratumumab (DRd) in 733 transplant ineligible (TIE) patients obtained from the Yale University Open Data Access (YODA) Project, which has an agreement with JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C.. Thrombotic events (TE), including both venous and arterial events (V/ATE) were examined with VTE events including deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial thrombophlebitis (SVT). Arterial events (ATE) included cerebrovascular accidents (CVA) defined as hemorrhagic, ischemic, or verebrobasilar strokes. The incidence and time to event of V/ATE were calculated and graded using the CTCAE v4, with Grade 1 representing nonactionable venous thrombosis, Grades 2-4 representing TEs requiring increasing higher levels of medical intervention, and Grade 5 indicating death was a result of the TE. Rates and time to events were compared between the DRd and Rd arms. Results. Of the included patients, median age was 72 years (range 64-72) and 48% were female. There was no signficant difference between baseline characteristics of sex, race, myeloma subtype, presence of high-risk cytogenetics, or ISS staging between patients that experienced a V/ATE event and those that did not. All grade V/ATE events were 18% (66/363) and 19% (70/365) in the DRd and Rd arms, respectively. Of these, most were VTE events in both arms (16%), with G2-4 actionable VTE event rate of 14.9% vs 14.8% for the DRd and Rd arms, respectively. G5 VTE events were 0.2% in both arms (no G5 ATEs). ATE were 2.2% and 2.7% in the DRd and Rd group, respectively, overall constituting a minority of events. The overall PE rate was higher in the DRd than Rd arm, 6.3% vs 4.7%, DVT was more frequent in the Rd arm, 9.6% vs 7.7%, and rates of SVT rates were similar between both arms at 1.9% and 2.2% for the DRd vs Rd arms, respectively (Table 1). Median time to onset of cumulative TEs was longer in DRd vs Rd arm, 7.15 (0.27 - 63.0) vs 4.65 (0.03 - 58.0) months, respectively. Among these, median time to onset of VTE was similar among the groups [6.57 (0.27 - 63.0) vs 4.48 (0.03 - 52.9) months, respectively] while the median time to onset of ATEs was longer in DRd vs Rd arm, 19.8 (1.70 - 26.6) vs 8.3 (0.67 - 58.5) months. The incidence of VTE events persisted past 24 months and incidence of ATE events increased over time (Figure 1). Analysis regarding prophylactic anticoagulation use and rates of TE based on prophylactic regimen are ongoing. Conclusion. This retrospective study reveals the highest reported rates of VTE in any modern therapy dataset. In patients with transplant ineligible NDMM, we show that the TE risk persists past 24 months of treatment in patients on DRd or Rd therapy. Similar to observations in the GRIFFIN trial, the addition of daratumumab did not increase the risk of TE. Our report highlights the critical need for further investigation of optimal prophylactic strategies and their duration for patients with NDMM.

Overexpression of miR-483-5p predicts venous thrombo-embolism onset in patients with lung cancer especially in high BMI cases.

Venous thromboembolism (VTE) is a common complication in patients with lung cancer. The important roles of microRNAs (miRNAs) in VTE have emerged, however, studies about the roles of miRNAs in VTE remain scarce. This study aimed to measure the expression of miR-483-5p in lung cancer patients with VTE, evaluate whether miR-483-5p could predict VTE onset in patients, and further evaluate its predictive value in patients with different BMI values. A total of 170 patients with lung cancer were recruited in this study, including 70 patients with VTE, and 110 patients with non-VTE. The expression of miR-483-5p was detected by quantitative real time PCR. Receiver operating characteristic analysis was used to screen VTE patients from non-VTE patients. Whether miR-483-5p was independently associated with VTE onset in lung cancer patients was evaluated by univariate and multivariate logistic regression analyses. miR-483-5p was higher in VTE patients than that in non-VTE patients. miR-483-5p was correlated with body mass index (BMI), hypertension, C-reactive protein (CRP), and platelet count in VTE patients. In addition, miR-483-5p had high diagnostic value to differentiate between VTE patients and non-VTE patients and served as an independent biomarker in predicting the VTE onset in lung cancer patients. Moreover, miR-483-5p had the highest diagnostic accuracy to screen VTE patients from non-VTE patients in patients with high BMI values. miR-483-5p, increased in VTE patients, can independently predict VTE onset in lung cancer patients especially in patients with high BMI values.

Venous Thromboembolism in Japanese Patients with Gynecologic Cancer.

Gynecologic cancer, including cervical, endometrial, and ovarian cancer, comprises the fifth leading type of cancer and is an important malignant disease in women. Previous studies in Western countries have reported respective prevalence rates for venous thromboembolism (VTE) of 3.3%-18.7%, 0.8%-8.1%, and 7.2%-20.9%. In this study, we aimed to identify the characteristics associated with VTE in Japanese patients. We carried out a retrospective cohort study to compare the clinicopathological characteristics of patients with each gynecologic cancer with and without concomitant VTE. Patients: Patients with cervical, endometrial, or ovarian cancer treated at Fukui Prefectural Hospital, Japan, from April 2010 to March 2020. Among 699 patients with gynecologic cancer, 50 developed VTE within 5 years after their cancer diagnosis, including 16/357 patients with cervical cancer (5.6%), 12/185 with endometrial cancer (6.8%), and 22/157 with ovarian cancer (14.6%). The 1-year mortality rate after symptomatic VTE onset was 47.8%. The VTE group included significantly more older patients and more patients with advanced cancer or poor performance status compared with the non-VTE group. There was no significant difference in the rate of surgical treatment. Symptomatic, but not asymptomatic VTE, was associated with shorter survival. Several baseline characteristics differed between patients with and without VTE. The incidences of VTE and some risk factors were similar in Japanese patients with gynecologic cancers compared with patients in other countries. Patients with VTE had some factors that worsened their prognosis, with patients with gynecologic cancer and symptomatic VTE having an especially poor prognosis.

Venous Thromboembolism following Two Doses of COVID-19 mRNA Vaccines in the US Population, 2020-2022.

The COVID-19 mRNA vaccine is one of the most effective strategies used to fight against COVID-19. Recently, venous thromboembolism (VTE) events after COVID-19 mRNA vaccination have been reported in various research. Such a concern may hamper the ongoing COVID-19 vaccination campaign. Based on the US Vaccine Adverse Event Reporting System data, this modified self-controlled case series study investigated the association of COVID-19 mRNA vaccination with VTE events among US adults. We found the VTE incidence rate in the recommended dose interval does not change significantly after receiving COVID-19 mRNA vaccines. This conclusion still holds if the analysis is stratified by age and gender. The VTE onset may not be significantly associated with COVID-19 mRNA vaccination.

P59-4 Analysis of symptomatic venous thromboembolism after pancreatic cancer chemotherapy

Patients with cancer have a higher tendency to present with venous thromboembolism (VTE) compared to patients without cancer. VTE is the second most common cause of death among patients with cancer. According to some reports, the risk of VTE in pancreatic cancer is the highest among all cancer types and was associated with poor overall survival and progression-free survival. Conventionally, the Khorana score has been devised as a predictor of VTE onset in patients with cancer. Most of these scoring systems are based on clinical studies including asymptomatic VTE.

Application of venous thromboembolism prophylaxis program in patients with colorectal cancer using the enhanced recovery after surgery protocol

IntroductionThe incidence of postoperative symptomatic venous thromboembolism (VTE) in western colorectal cancer is 1.1–2.5%. Anticoagulation and mechanical devices are recommended for moderate-to high-risk patients. Hospital stay and immobilization, as risk factors for VTE, are reduced by enhanced recovery after surgery (ERAS). This study aimed to evaluate short- and long-term outcomes for a VTE prophylaxis program after minimally invasive colorectal cancer surgery with ERAS protocol. In addition, predicting factors associated with VTE were investigated. Materials and methodsWe included 1043 patients diagnosed with colorectal cancer who required surgical treatment between January 2017 and December 2019 at a single institution. The patients enrolled followed the VTE prophylaxis program. ResultsFive (0.5%) patients developed symptomatic VTE, and the median follow-up period was 21 months. The Caprini score for all VTE patients was ≤8 points; thus, only mechanical prophylaxis was applied. The incidence rate of postoperative symptomatic VTE was only 0.5%. There was no association between variables considered as associated with VTE onset, such as age, perioperative complication, and length of postoperative day. TNM staging (OR 2.44, 95% CI 1.4–4.16, p = 0.001) and the Caprini score (OR 1.75, 95% CI 1.1–2.8, p = 0.001) were associated with VTE onset. ConclusionAlthough pharmacological prophylaxis was only performed for Caprini scores ≥9, the VTE incidence rate of patients with colorectal cancer undergoing VTE prophylaxis program was 0.6%; 0.7% is the incidence criterion of the moderate group recommended for pharmacological prophylaxis. Continuous follow-up is required for patients with advanced-stage colorectal cancer with high-risk Caprini scores.

Pathogenesis of Two Faces of DVT: New Identity of Venous Thromboembolism as Combined Micro-Macrothrombosis via Unifying Mechanism Based on "Two-Path Unifying Theory" of Hemostasis and "Two-Activation Theory of the Endothelium".

Simple SummaryDVT is an intravascular blood clotting disorder that can be a life-threatening disease, particularly if it occurs in critically ill patients. Typically, distal DVT develops following a vascular injury associated with incidental trauma commonly involving lower extremities, which is transient and benign condition localized in the lower legs as solitary lesion. However, proximal/central DVT (i.e., venous thromboembolism) typically occurs in association with critical illnesses such as sepsis, diabetes, hypertension, cancer, autoimmune disease and others in the hospitalized patient, especially in the ICU. Recognition of different pathogenesis between distal DVT and proximal/central DVT is critically important because the prognosis is poorer in VTE. Its therapeutic approach should be different from distal DVT. The aim of this review is to identify the pathogenesis of two different types of DVT based on in vivo hemostatic mechanisms, which can explain their distinct phenotypes by clinical characteristics, laboratory data and imaging findings. An appropriate preventive measure can be put into the practice to avoid the onset of VTE. Additionally, should VTE be developed, proper and rational therapeutic regimen based on its pathogenesis can be designed for clinical trials to improve the outcome.Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the venous system but with varying degree of clinical expression related to its localization and severity. The genesis of two phenotypes of DVT differing in clinical features and prognostic outcome can be identified by their unique hemostatic mechanisms. Two recently proposed hemostatic theories in vivo have clearly defined the character between “microthrombi” and “macrothrombus” in the vascular system. Phenotypic expression of thrombosis depends upon two major variables: (1) depth of vascular wall damage and (2) extent of the injury affecting the vascular tree system. Vascular wall injury limited to endothelial cells (ECs) in sepsis produces “disseminated” microthrombi, but intravascular injury due to trauma extending from ECs to subendothelial tissue (SET) produces “local” macrothrombus. Pathogen-induced sepsis activates the complement system leading to generalized endotheliopathy, which releases ultra large von Willebrand factor (ULVWF) multimers from ECs and promotes ULVWF path of hemostasis. In the venous system, the activated ULVWF path initiates microthrombogenesis to form platelet-ULVWF complexes, which become “microthrombi strings” that produce venous endotheliopathy-associated vascular microthrombotic disease (vEA-VMTD) and immune thrombocytopenic purpura (ITP)-like syndrome. In the arterial system, endotheliopathy produces arterial EA-VMTD (aEA-VMTD) with “life-threatening” thrombotic thrombocytopenic purpura (TTP)-like syndrome. Typically, vEA-VMTD is “silent” unless complicated by additional local venous vascular injury. A local venous vessel trauma without sepsis produces localized macrothrombosis due to activated ULVWF and tissue factor (TF) paths from damaged ECs and SET, which causes distal DVT with good prognosis. However, if a septic patient with “silent” vEA-VMTD is complicated by additional vascular injury from in-hospital vascular accesses, “venous combined micro-macrothrombosis” may develop as VTE via the unifying mechanism of the “two-path unifying theory” of hemostasis. This paradigm shifting pathogenetic difference between distal DVT and proximal/central DVT calls for a reassessment of current therapeutic approaches.

Assessment of Venous Thromboembolism Risk Based on the Khorana Predictive Model and Compliance with Prophylactic Anticoagulation at a Regional Cancer Center- a Quality Improvement Study

Background:Malignancy is an independent risk factor for venous thromboembolism. Factors like site of the primary cancer, associated comorbidities, obesity, and baseline cytopenias play an important role in predicting the risk in cancer patients. Several risk assessments models have been proposed in the literature, however, the Khorana risk predictive model is the most favored tool used in the literature. Patient characteristics like site of primary, baseline hemoglobin/platelets/WBC and BMI are the main components of this scoring system. Patients are classified into low (0), intermediate (1-2) and high (> 3) risk groups. Low dose prophylactic anticoagulation (Apixaban 2.5 mg BID or Rivaroxaban 10 mg daily) for up to 6 months is indicated in patients with score 2 or higher.Methods:83 patients with a new cancer diagnosis in the years 2018 and 2019 who received chemotherapy and developed a venous thromboembolism (VTE) after the cancer diagnosis were identified from the cancer registry at Edwards Comprehensive Cancer Center. All the components of Khorana score including patient's baseline body mass index (BMI), white blood cell count (WBC), hemoglobin, platelet count and site of the primary were collected. Compliance with prophylactic anticoagulation (Khorana score =/>2) was evaluated.Results:Among 83 patients identified, 61 % and 39 % were female and males, respectively with a mean age of 59 years. The mean duration of onset of VTE was 18 months from the time of cancer diagnosis. The mean Khorana score was 1.1. 34 % of patients(n=28) were found to have a Khorana score of =/> 2 and prophylactic anticoagulation was indicated. Only 7 % of patients (n=2) received prophylactic anticoagulation. The reason for no prophylactic anticoagulation was not documented in all the cases.Conclusion:In patients with a higher risk of VTE, a very low compliance rates for prophylactic anticoagulation were found at our cancer center. Poor documentation and failure to address the risk of VTE are possible reasons for the low compliance rates. Necessary steps needed to improve the compliance rates are warranted including education of the healthcare providers about current available guidelines to decrease risk of VTE in cancer patients. Dedicated lectures and sessions will be organized and educational materials highlighting the importance of VTE risks and prophylactic anticoagulation will be provided to the healthcare providers at the cancer center. DisclosuresNo relevant conflicts of interest to declare.

Diagnostic and Prognostic Value of Immune/Inflammation Biomarkers for Venous Thromboembolism: Is It Reliable for Clinical Practice?

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), has been an important cause of sudden in-hospital death. Studies have shown that the immune/inflammatory response plays an important role in the pathogenesis of vascular disease, with representative markers in the blood including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune/inflammatory index (SII), etc. However, there is a variety of immune/inflammatory indicators. Moreover, most previous studies have been single-center investigations involving one or two indicators, with varying nature of cases, number of cases and study objectives, thereby making it difficult to reach consensus conclusions with good clinical guidelines. This article reviews the clinical value of immunoinflammatory indicators for VTE based on previous studies, including the diagnostic and prognostic capabilities. In conclusion, NLR provides promising predictive capability for the onset and prognosis of VTE and deserves extensive application in clinical practice. PLR also has certain diagnostic and prognostic value, but further studies are warranted to identify its reliability and stability. Monocytes, eosinophils and platelet-related indicators show some clinical association with VTE, although the predictive capabilities are mediocre. SII is of promising potential value for VTE and deserves further investigations. This review will provide new clues and valuable clinical guidance for the diagnosis and therapy of VTE.

Clozapine-Related Thromboembolic Events.

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. Venous thromboembolism (VTE) is a rare side effect of clozapine which can be fatal. This article summarizes current evidence regarding the risk of VTE associated with the use of clozapine. We performed a PubMed (MeSH) and Google Scholar search for the last two decades. Studies or case reports performed in humans were included in the review, of which 42 case reports of patients taking clozapine at VTE onset were included in the analysis of this review. According to the articles reviewed, the mean age was 42.9 years, with more males (71.43%) than females (28.57%). The average clozapine dose was 285.62 mg/day. VTE onset occurred within the first six months in 71.8% of the cases. Overall, 70.37% of the patients had comorbidities, and 87.5% had risk factors for VTE. In total, 68.57% were prescribed other medications at VTE onset, and 60% were being treated with another antipsychotic concomitantly. Finally, 32.5% of the patients died, while 67.5% survived. In 60% of the cases, clozapine was discontinued after VTE. In our literature review, we observed that among clozapine users, VTE occurred at a wide dose range, and most of the events occurred within the first six months. As many patients who are prescribed clozapine have risk factors for VTE, the risk should be considered at the time of prescribing. Further research should be conducted to elucidate the risk of VTE in clozapine users and the benefits of thromboprophylaxis.

Effectiveness of a multidisciplinary care program for the management of venous thromboembolism in cancer patients: a pilot study.

Treatment of Venous thromboembolism (VTE) in cancer patients is challenging due to higher risk of VTE recurrence or bleeding under anticoagulants. We assessed the effectiveness of a dedicated "Allo-Thrombosis Cancer" multidisciplinary care program (AlloTC-MCP) that incorporated individualized care, regular follow-ups, telephone counselling, and a patient education program. From September 2017 to October 2019, 100 consecutive cancer patients with new VTE onset were enrolled in this observational single-center prospective pilot study and received standard (control group, n = first 50 patients enrolled) or AlloTC-MCP care (n = next 50 patients enrolled) over a 6-month VTE treatment follow-up period. Primary end-point was the percentage of adherence to the International Clinical Practice Guidelines (ITAC-CPGs) at 6 (M6) month follow-up. Among the 100 patients with different cancer types (22% genitourinary, 19% breast, 16% gastrointestinal, 15% lymphoma, 11% lung and 17% others), 51 patients (61%) had metastatic disease and 31 (31%) received chemotherapy alone. Main baseline cancer and VTE clinical characteristics did not differ between the 2 groups. Adherence rates to ITAC-CPGs was significantly higher in the AlloTC-MCP group (100% (M0), 72% (M3) and 68% (M6)) compared with the control group (84% (M0), 8% (M3) and 16% (M6)). Quality of Life (QoL) was significantly improved in the AlloTC-MCP group 6months after inclusion. The "AlloTC-MCP" was associated with improved adherence to ITAC-CPGs and merits further expansion.

Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi

The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism.

Thromboprophylaxis Measures to Prevent Venous Thromboembolism in Hospitalized Patients

Venous thromboembolism (VTE) is a serious complication in hospitalized patients and is the most frequent cause of preventable death in these patients, in addition to being the third cause of death of cardiovascular origin. Even though the loss of recent or continued mobility represents an important predisposition related to the onset of VTE, there are no clear and uniform criteria for defining the concept of immobility. Despite this, it is currently known that the early mobilization and other non-pharmacological thromboprophylactic measures of the patient in the medical or surgical clinic is an essential measure for his full recovery and satisfactory prognosis. Therefore, it is always important to prescribe preventive multiprofessional care, such as lateral decubitus variation, bed positioning, passive continuous movements apparatus as use of a cycle ergometer (CE), compressive socks, intermittent pneumatic compression (IPC), electric stimulation, sitting position, orthostatism, transfer from bed to chair, walking, and insertion of a filtering device in the lower portion of the main human vein in order to guarantee recovery quickly, safely and free from the risk of developing fatal complications such as pulmonary thromboembolism (PTE). Our objective in this article is to briefly summarize the main non-pharmacological thromboprophylaxis measures that help prevent venous embolism, in addition to addressing other mechanical resources used to prevent complications of thromboembolic events described in the literature on this topic.

Risk Prediction and New Prophylaxis Strategies for Thromboembolism in Cancer.

In the general population, the incidence of thromboembolic events is 117 cases/100,000 inhabitants/year, while in cancer patient incidence, it is four-fold higher, especially in patients who receive chemotherapy and who are affected by pancreatic, lung or gastric cancer. At the basis of venous thromboembolism (VTE) there is the so-called Virchow triad, but tumor cells can activate coagulation pathway by various direct and indirect mechanisms, and chemotherapy can contribute to VTE onset. For these reasons, several studies were conducted in order to assess efficacy and safety of the use of anticoagulant therapy in cancer patients, both in prophylaxis setting and in therapy setting. With this review, we aim to record principal findings and current guidelines about thromboprophylaxis in cancer patients, with particular attention to subjects with additional risk factors such as patients receiving chemotherapy or undergoing surgery, hospitalized patients for acute medical intercurrent event and patients with central venous catheters. Nonetheless we added a brief insight about acute and maintenance therapy of manifested venous thromboembolism in cancer patients.