Risk Of VTE Research Articles

Factor Xa inhibitors versus low molecular weight heparin for the treatment of cancer associated venous thromboembolism; A meta-analysis of randomized controlled trials and non-randomized studies.

We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

Glucocorticoids and Risk of Venous Thromboembolism in Asthma Patients Aged 20-59 Years in the United Kingdom's CPRD 1995-2015.

BackgroundGlucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma.MethodsWe conducted a nested case–control study among patients aged 20–59 years with asthma who received at least one glucocorticoid prescription during 1995–2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use.ResultsThe adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6–2.3), 1.4 (1.1–1.8), and 1.2 (0.9–1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7–4.5) and 1.5 (1.3–1.8), respectively.ConclusionCurrent and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

Development and Validation of a Nomogram to Predict the Probability of Venous Thromboembolism in Patients with Epithelial Ovarian Cancer.

ObjectiveTo identify predictive factors and develop a nomogram to predict the probability of venous thromboembolism for epithelial ovarian cancer patients. Methods: Our study cohort was composed of 208 EOC patients who had received initial treatment in Sun Yat-sen Memorial Hospital from January 2016 to March 2020. Clinicopathological variables predictive of VTE were identified using univariate logistic analysis. A multivariate logistic regression model was used to select the predictive factors used for nomogram. The accuracy of nomogram was evaluated by the Concordance index (C-index), the area under the receiver–operator characteristic (ROC) curve, area under concentration-time curve (AUC) and the calibration curve. Results: Advancing age (hazard ratio [HR], 1.042; 95% confidence interval [CI], 1.000-1.085; P = .048), higher D-dimer level (HR, 1.144; 95%CI, 1.020-1.283; P = .022), lower PR immunohistochemical positive rate (HR, 0.186; 95%CI, 0.034-1.065; P = .059) and higher Ki67 immunohistochemical positive rate (HR, 4.502; 95%CI, 1.637-12.380; P = .004) were found to be independent risk factors for VTE, and were used to construct the nomogram. The C-index for VTE prediction of the nomogram was 0.75. Conclusions: We constructed and validated a nomogram able to quantify the risk of VTE for EOC patients, which can be applied in recognizing EOC patients with high risk of VTE.

The new transdermal contraceptive patch expands available contraceptive options: Does it offer protection with less VTE risk?

The new transdermal contraceptive patch expands available contraceptive options: Does it offer protection with less VTE risk?

Risk of venous thromboembolism during the use of oral estrogen-progestogen hormone therapies in light of most recent research findings.

Two important studies evaluating the safety profile of oral estrogen-progestogen hormonal therapies conducted in standard clinical practice with respect to the venous system were recently published.A large prospective controlled cohort study (PRO-E2) based on the non-inferiority design has shown that the relative risk of developing venous thrombosis (VTE) in women using combined oral hormonal contraceptives (COHC) containing 17β-estradiol (1.5 mg) and nomegestrol acetate (2.5 mg) (E2/NOMAC) was not statistically different from that in users of COHC containing ethinylestradiol and levonorgestrel (EE/LNG).The aim of the recently presented study was to compare the risk of VTE in patients treated with a product for oral continuous combined menopausal hormone therapy containing 1 mg of 17ß-estradiol and 100 mg of micronized progesterone (1 mgE2/100 mgP4) with patients taking conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA). The study was based on an analysis of records retrieved from a US health insurance database, and was therefore concerned the real-life clinical practice. The hazard ratio of VTE when comparing 1 mgE2/100 mgP4 with CEE/MPA was 0.70 (95% CI: 0.53–0.92). The difference was found to be statistically significant (p < 0.05).The rewieved studies provide further evidence that the use of hormones bioidentical with endogenous steroids in oral contraception and menopausal hormone therapy creates an opportunity to combine high efficacy with a favorable safety profile.

The new algorithm for stratification of the risk of venous thromboembolic events in elective neurosurgery and its prognostic significance

To assess predictive value of the developed algorithm for elective neurosurgical interventions. The study included 7914 patients who underwent surgery between January 2018 and December 2019. According to the algorithm, we identified the groups of low (1536 (19%) patients), moderate (4554 (58%) patients) and high risk (1824 (23%) patients). Moreover, patients were divided into subgroups depending on surgical procedure. We analyzed the incidence of VTE and mortality in all groups. Of VTE with a 95% confidence interval in the low-risk group was 0.65% [0.26; 1.04], in the moderate risk group - 1.82% [1.47; 2.24], in the high-risk group - 12.61% [11.02; 14.09]. When comparing various surgical interventions, we revealed more common VTE after vascular microsurgery (15.62%), in patients with brain tumors (12.63%) and spinal cord tumors (6.52%). The risk stratification algorithm has demonstrated its convenience and significant predictive value for determining the risk of VTE among elective neurosurgical patients. In addition, different incidence of VTE was demonstrated in patients with various neurosurgical diseases.

Assessment of venous thromboembolism prophylaxis practice in medical-surgical adult ICU: A cross sectional study

BackgroundVenous thromboembolism (VTE) is a condition in which blood clots develop in the deep veins, especially in the lower limb veins. Intensive care unit (ICU) patients have a greater risk of thrombotic events due to additional risk factors such as immobilization, mechanical ventilation, and central catheters. In medical-surgical critically ill patients, the occurrence of symptomatic or asymptomatic DVT without thromboprophylaxis is 13–31%. ObjectiveTo assess the practice of venous thromboembolism prophylaxis in medical-surgical adult ICU. MethodsAll consecutive critically ill patients in ICU from January 10, 2021, to Jun 9, 2021, were included in the study. Data were collected using reviewing the patient chart and interviewing the responsible body in ICU including the residents and nurses. The same patient was not included twice within the same cycle, or in the second cycle, if he/she was still in the ICU at the time of the second cycle excluded by observing previous patient ID. The data was processed and analyzed by using SPSS version 20 and Microsoft Excel 2010. ResultA total of 90 surgical-medical ICU patients were observed. All of the patients in the sample were receiving some form of VTE prophylaxis (100%), but none of them (0%) had the risk stratification documented in the chart. Conclusionand recommendations: It's critical to emphasize the importance of VTE risk stratification documentation in patients' charts. We recommend that the ICU staffs to follow a specific protocol for VTE risk stratification and prophylaxis dosing based on well-known guidelines and recommendations and that once that protocol is implemented, an awareness and education campaign be applied.

Benefits and risks of hormonal replacement therapy

Menopause, defined as the permanent cessation of menstruation resulting from the loss of the ovarian function, has gradually become a fundamental health concern. Menopause hormonal replacement therapies (HRT) were initially developed with the purpose to alleviate the estrogen deficiency induced symptoms. Currently, HRT is approved by the FDA (Food and Drug Association) for four indications: bothersome vasomotor symptoms (VMS); prevention of bone loss; hypoestrogenism caused by hypogonadism, castration, or premature ovarian failure and genitourinary symptoms. For patients younger than 60 years or within the first 10 years from menopause onset and without contraindications, the benefit-risk ratio should be favorable for treatment of VMS and for preventing bone loss and related fractures. For women who initiate HRT more than 10 / 20 years from menopause onset (or aged 60 years or older), the benefit-risk balance seems to be less favorable than for younger patients because of greater absolute risks of cardiovascular disease, stroke and VTE. Even though the management of menopausal symptoms through pharmacological and cognitive-behavioral therapy improves quality of life of affected women in the short term, there is a need for the development of strategies to modify menopausal health risks, in the long term.

Incidence of VTE in Patients With OSA: A Cohort Study

Previous studies suggesting that OSA may be an independent risk factor for VTE have been limited by reliance on administrative data and lack of adjustment for clinical variables, including obesity. Does OSA confer an independent risk of incident VTE among a large clinical cohort referred for sleep-disordered breathing evaluation? We analyzed the clinical outcomes of 31,309 patients undergoing overnight polysomnography within a large hospital system. We evaluated the association of OSA severity with incident VTE, using Cox proportional hazards modeling accounting for age, sex, BMI, and common comorbid conditions. Patients were of mean age 50.4 years, and 50.1%were female. There were 1,791 VTE events identified over a mean follow-up of 5.3 years. In age- and sex-adjusted analyses, each 10-event/h increase in the apnea-hypopnea index was associated with a 4%increase in incident VTE risk (hazard ratio [HR], 1.04; 95%CI, 1.02-1.06). After adjusting for BMI, this association disappeared (HR, 1.01; 95%CI, 0.99-1.03). In contrast, nocturnal hypoxemia had an independent association with incident VTE. Patients with > 50%sleep time spent with oxyhemoglobin saturation< 90%are at 48%increased VTE risk compared with those without nocturnal hypoxemia (HR, 1.48; 95%CI, 1.16-1.69). In this large cohort, we found that patients with more severe OSA as measured by the apnea-hypopnea index are more likely to have incident VTE. Adjusted analyses suggest that this association is explained on the basis of confounding by obesity. However, severe nocturnal hypoxemia may be a mechanism by which OSA heightens VTE risk.

Clinical outcomes of pharmacological thromboprophylaxis among patients with intracerebral hemorrhage: Systematic review and meta-analysis

ObjectiveEfficacy and safety of pharmacologic thromboprophylaxis after an episode of intracerebral hemorrhage remains unclear. This meta-analysis aimed at comparing the clinical outcomes of intracerebral hemorrhage patients with or without pharmacologic thromboprophylaxis. MethodsWe performed a comprehensive literature review of PubMed to identified relevant studies. The primary and secondary endpoints included venous thromboembolism, deep venous thrombosis, pulmonary emboli, rebleeding, hematoma enlargement (defined as increase in hematoma volume of ≥33%), major disability (defined as modified Rankin score of 3–5), and death. Pooled outcomes were estimated by fitting random effects model with restricted maximum likelihood method. A total of 8 original studies including 3893 patients were analyzed. ResultCompared to the control group, pharmacologic thromboprophylaxis was associated with a lower risk of pulmonary embolism (odds ratio [OR]: 0.34, 95% CI: 0.15–0.80, P = 0.01). There was no significant difference in the risk of DVT (OR: 0.75; [95% CI: 0.37–1.53], P = 0.44) and VTE (OR: 0.65; [95% CI: 0.34–1.25], P = 0.20). Finally, anticoagulation was not associated with an increase rate of major disability (OR:1.36; [95% CI: 0.57 – 3.23], P = 0.48), rebleeding (OR: 0.35; [95% CI: 0.10–1.19], P = 0.09), hematoma enlargement (OR:1.34; [95% CI: 0.58–3.12], P = 0.49), or death (OR:0.90; [95% CI: 0.68–1.19], P = 0.46). ConclusionAmong patients with intracerebral hemorrhage, pharmacologic thromboprophylaxis was associated with a significant reduction in pulmonary embolism, without an increase in rebleeding or hematoma enlargement. The results of this meta-analysis need to be further validated in large scale clinical trials.

Screening for venous thrombotic events in patients presenting with pelvis and acetabular fractures: A new practice based on a prospective study

IntroductionPelvic fractures are complex fractures associated with a high risk of venous thromboembolic complications (VTE) and up to a 10% risk of fatal pulmonary embolism. We aimed to reduce perioperative morbidity and mortality using a systematic screening protocol and secondly to evaluate this protocol and identify VTE risk factors. MethodsThis was a prospective monocentric study involving 100 consecutively enrolled patients. The protocol included a venous ultrasound examination of the inferior vena cava and lower limbs and abdominopelvic CT venography within 48 h prior to surgery. The evaluation criteria were the mortality and complication rates. Secondary endpoints were the rate of VTE events and the identification of risk factors. ResultsOne patient died on D1 postoperatively of a massive pulmonary embolism. Migration of a vena cava filter was reported for another. No thrombotic recurrence or hemorrhagic complications were reported. The rate of VTE events was 21%, of which 90% were pre-operative asymptomatic events. CT venography did not show superiority over ultrasound. Patients with greater fracture displacement, preoperative infection, higher platelet counts, or having had a preoperative transfusion were at a higher risk of developing deep vein thrombosis (DVT). ConclusionsThe rate of asymptomatic VTE events in pelvic fractures is extremely high and leads to propose the following recommendations: (1) they should be preoperatively investigated by ultrasound and (2) a vena cava filter must be placed in cases of proximal DVT and the surgery postponed to allow anticoagulation treatment for at least 48 h, regardless of the type of thrombosis. Level of evidenceLevel II. Study typeDiagnostic test.

Abstract 9193: Peripheral Artery Disease and the Risk of Venous Thromboembolism

Introduction: Peripheral artery disease impacts 202 million patients worldwide and is commonly diagnosed via ankle-brachial index. PAD is associated with endothelial dysfunction, which is also common to venous thromboembolism formation. Despite the suspected overlap in pathogenesis, few studies exist investigating the association between these pathologies. We investigated whether PAD with low or elevated ABI is an independent risk factor for VTE. Methods: We reviewed medical records of patients ≥18 years old undergoing ABI measurement with or without PAD symptoms from 01/01/1996 to 08/31/2018 and classified patients by ABI: severely low (ABI 0.00-0.39), moderately low (0.40-0.69), mildly low (0.70-0.90), borderline (0.91-0.99), normal (1.00-1.40), and elevated (&gt;1.40). The primary outcome was incident VTE event after ABI measurement, defined as deep vein thrombosis or pulmonary embolism. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals after adjusting for age, sex, active smoking, cancer or VTE history, thrombophilia, anticoagulation, and revascularization within 14 days of VTE. Results: In 39,384 unique patients (mean age 66.3±14.2 years, median follow-up 34 months), 5,141 VTE events were observed. Increased VTE risk was observed in PAD patients with severely low ABI (HR 1.26, 95%CI [1.02, 1.29]) compared to patients with normal ABI after multivariable regression. Patients with elevated ABI did not demonstrate an increased risk of VTE. Conclusions: Patients with severe PAD are at higher risk for VTE than patients with normal ABI, which may be due to a multifactorial pathophysiology of profound endothelial injury as well as immobility due to claudication. Further exploration of VTE incidence in patients with severe PAD stratified by functional status is warranted to determine the optimal strategy to minimize thromboembolic morbidity and mortality in this population.

Routine use of LMWH prophylaxis is associated with a lower incidence of venous thromboembolic events following an ankle fracture

BackgroundVenous thromboembolic events (VTE) are well-known and serious complications following a trauma to the lower extremities. There is an ongoing debate on the benefit of low-molecular-weight heparin (LMWH) as prophylaxis following ankle fracture treatment. We examined the association between the incidence of VTE and the use of LMWH-prophylaxis following an ankle fracture, as well as factors affecting the risk of VTE. MethodsIn this retrospective cohort study, data on ankle fractures and fracture treatment from the Swedish Fracture Register was linked to data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Patients with VTE and patients who received LMWH prophylaxis were identified. The treating orthopedic departments were sent a questionnaire about their guidelines regarding the use of LMWH prophylaxis. Results222 cases of diagnosed VTE were identified among 14,954 ankle fractures. Orthopedic departments with higher-than-average use of LMWH prophylaxis among non-operatively treated ankle fractures had a lower incidence of VTE (OR 0.60, CI 0.39–0.92). Among operatively treated patients, departments with a guideline for the routine use of LMWH prophylaxis also had lower incidence of VTE (OR 0.56, CI 0.37–0.86). A later onset of VTE was seen among patients prescribed LMWH prophylaxis, with a mean of 56 days to onset (CI 44–67), compared to 39 days (CI 33–45) in patients without prescribed prophylaxis. During the first two weeks following injury, there was only one case of VTE in patients with prescribed LMWH, compared to 39 cases of VTE among patients without prescribed prophylaxis. ConclusionsRoutine use of LMWH in patients with operatively treated ankle fractures was associated with a lower incidence of VTE. A more frequent use of LMWH among patients with non-operatively treated ankle fractures were associated with a lower incidence of VTE. The onset occurred later among patients with LMWH-prophylaxis who still suffered a VTE.

Venous Thromboembolism in Surgical Lung Cancer Patients: A Provincial Population-Based Study

BackgroundVenous thromboembolism (VTE) is a significant cause of morbidity and mortality in surgical patients. Thoracic surgery patients are at increased risk due to inherent technical and disease-specific factors. Other surgical specialties have adopted postdischarge extended VTE prophylaxis; however evidence is scarce in thoracic surgery. This study aims to identify VTE risk factors and associated mortality among surgical lung cancer patients. MethodsUsing administrative databases all patients in the province of Ontario undergoing lung cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery between patients with and without VTE. ResultsOf 65,513 patients diagnosed with lung cancer, 12,626 (19.3%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively was 1.3% and 2.7%, respectively. Open and more extensive resections carried an increased VTE risk, with pneumonectomy conferring the highest risk (odds ratio, 2.36; P < .001). Stage III and IV disease carried a 3.19 and 4.97 times higher risk of VTE, respectively, compared with stage I (P < .001). The hazard ratio for mortality at 1 year for patients with VTE was 2.01 (P < .001). Patients suffering a VTE had reduced 5-year survival. ConclusionsPatients undergoing pneumonectomy and those with advanced stage have an increased VTE risk. Patients suffering a thrombotic complication have an increased risk of mortality and decreased 5-year survival. Accordingly strategies to reduce VTE risk should be considered in patients undergoing high-risk operations to reduce the mortality of VTEs.

BIOM-27. INTEGRATED PREDICTION OF VENOUS THROMBOEMBOLISM IN GLIOMA PATIENTS

Abstract BACKGROUND Venous thromboembolism (VTE) is a debilitating and life-threating condition that is common in patients with cancer, especially glioma. There are no widely-accepted guidelines for antithrombotic prophylaxis in glioma patients, in part because of the risk of iatrogenic intracerebral hemorrhage. Effective VTE prediction models exist for patients with other cancers, but not glioma. Our prior publications suggested a protective role of IDH mutation (IDHmut) against VTE, as well as a positive association between elevated circulating Tissue Factor (TF), a procoagulant secreted by cancers, and VTE in glioma patients. Others have recently found a correlation between podoplanin, a platelet activator, and cancer-associated VTE, but this has not yet been proven in gliomas. Our objective was to develop a multidimensional VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. METHODS The Northwestern University Nervous System Tumor Bank provided preoperative arterial blood, tumor tissue, and clinical-pathologic data from 254 grade II-IV glioma patients over a 4-year interval. Molecular profiling was done by GlioSeq NGS. RESULTS Forty-six out of 254 grade II-IV glioma patients (18%) experienced VTE during their disease course. VTE was associated with worse median overall survival (18 vs. 54 months, P&amp;lt; 0.001). Positive risk factors for VTE included advanced patient age, high body mass index, high glioma grade, prior history of VTE, coronary artery disease, hyperlipidemia, hypertension, and elevated circulating TF activity, among other variables. While tumor expression of podoplanin positively correlated with VTE, circulating podoplanin did not. Among molecular markers, the strongest was IDHmut, being associated with greatly reduced VTE risk (OR=0.28; 95% CI=0.12-0.64, P=0.001). CONCLUSIONS This study identified multiple risk factors for glioma-associated VTE. Using these data, we have developed a web-based multivariable integrated prediction calculator to identify glioma patients who would benefit the most from prophylactic anticoagulation.

Venous thromboembolism in patients with surgically treated ankle fractures.

In patients with rotational ankle fracture, we compare the rate of venous thromboembolism development between patients who received chemoprophylaxis vs those patients that received none. Retrospective cohort study. Level I trauma center. Between 2014 and 2018, we identified 483 patients with rotational ankle fracture that had no VTE risk factors, were under 70years of age, and had an isolated injury. Chemoprophylaxis vs no chemoprophylaxis after open reduction internal fixation of a rotational ankle fracture. Development of VTE was the primary outcome. Secondary outcomes included wound problems, infection, hematoma, or non-union. There were 313 patients that received no prophylaxis and 170 patients that received chemoprophylaxis after operative fixation of an isolated ankle fracture. Demographics including age, gender, body mass index, and ASA class were similar between groups. The rate of DVT/PE was 3.5% in those without DVT prophylaxis, and 4.1% in those on DVT prophylaxis with no significant differences found (p = 0.8). There was no significant difference in wound complication (no VTE prophylaxis-3.7% vs VTE prophylaxis-2.5%, p = 0.7) or infection rates (no VTE prophylaxis-3.8% vs VTE prophylaxis 4.1%, p = 1.0) between groups. No difference was detected in the rate of symptomatic DVT or PE in patients based on chemoprophylaxis. Our results support the conclusion that the use of chemoprophylaxis may remain surgeon preference and based on patient risk factors for VTE development. Level III-retrospective cohort study.

Efficacy and Safety of Apixaban for Primary Prevention of Thromboembolism in Cancer Patients with a Newly Inserted Central Venous Catheter: A Post-Hoc Analysis of the Avert Trial

BackgroundVenous thromboembolism (VTE) is a common complication in ambulatory patients with cancer initiating systemic chemotherapy. Central venous catheters (CVCs) used for chemotherapy administration are associated with a heightened risk of VTE in this patient population. Primary thromboprophylaxis using a direct oral anticoagulant decreases the risk of VTE without significantly increasing the risk of major bleeding complications in ambulatory cancer patients at intermediate-to-high risk of VTE with a Khorana risk score of ≥ 2. We sought to determine the efficacy and safety of apixaban in intermediate-to-high risk patients with cancer and a CVC.MethodsThis post-hoc analysis was done using the AVERT trial data, which was a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban for primary thromboprophylaxis in intermediate-to-high risk patients with cancer initiating chemotherapy. The primary efficacy outcome was major VTE within 180 days of randomization and the primary safety outcome was major bleeding. The hazard ratios (HRs) for the primary efficacy and safety outcomes in patients with and without CVC were calculated using a Cox regression model controlling for age, gender, and study center.ResultsA total of 217 patients were included in the subgroup analyses with 126 and 91 patients receiving apixaban or placebo, respectively. The baseline characteristics are depicted in Table 1. Major VTE occurred in 6 (4.8%) patients in the apixaban group and 17 (18.7%) patients in the placebo group (HR 0.26; 95% CI, 0.14-0.47; p<0.0001). Major bleeding occurred in 2 (1.6%) patients in the apixaban group and 2 (2.2%) patients in the placebo group (HR 0.69; 95% CI, 0.20-2.35; p=0.556).ConclusionsPrimary thromboprophylaxis with apixaban in patients with cancer and a CVC seems to reduce the risk of VTE without increasing the risk of major bleeding. Future studies are needed to confirm these findings. [Display omitted] DisclosuresWells: BMS/Pfizer: Research Funding; Bayer: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Servier: Honoraria. Carrier: Bristol Myers Squibb: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; Servier: Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Efficacy and Safety of Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients with Cancer and Central Venous Catheter: A Systematic Review and Meta-Analysis

▪BackgroundVenous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is also increased following the insertion of a central venous catheter (CVC) for chemotherapy deliverance and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and newly inserted CVC are unclear.ObjectiveWe sought to assess the rates of VTE and major bleeding complications to determine the safety and efficacy of primary thromboprophylaxis in adult patients with cancer and a CVC.MethodsA systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis or observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively.ResultsA total of 9 RCTs (3155 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving primary thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32 to 0.82, p < 0.01, I² = 52%) (Figure 1). The rate of major bleeding complication was not increased in patients receiving thromboprophylaxis (0.9% vs. 0.7%; OR 1.12, 95% CI 0.29 to 4.40, p = 0.87, I² = 32%) (Figure 2).ConclusionsPrimary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings. [Display omitted] DisclosuresWang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding. Ikesaka: LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wells: Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; BMS/Pfizer: Research Funding; Servier: Honoraria. Carrier: Servier: Honoraria; Boehringer Ingelheim: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Clinical Characteristics Associated with Venous Thromboembolism in Patients with Non-APL Acute Myeloid Leukemia

INTRODUCTIONVenous thromboembolism (VTE) is an important complication of many cancers. Although more widely recognized in solid tumors, VTE is still an appreciable cause of morbidity and mortality among patients with hematologic malignancies. For example, acute promyelocytic leukemia (APL) is a well-recognized risk factor for disseminated intravascular coagulation (DIC), which can lead to thrombosis. Patients with non-APL AML are also at increased risk for VTE, though the exact mechanisms are currently unclear. Thus, we sought to explore how patient demographics, comorbidities, hematologic factors, coagulation parameters, and cytogenetic and molecular profiles impact the incidence of VTE in patients with non-APL AML. METHODSThis was a retrospective observational case-control study of 120 non-APL AML patients treated at the University of Wisconsin-Madison. The electronic health record was manually reviewed for extraction of the relevant clinical information. Coagulation parameters assessed included INR, PTT, fibrinogen, D-dimer, and fibrin monomer. Coagulation data were collected both at diagnosis and during the first 7 days of induction, if applicable. Cytogenetics was categorized based on the presence of a normal karyotype or not. Genomic data were subdivided into eight different functional categories of genes that are commonly mutated in AML. Other factors that could potentially increase the risk of thrombosis were also analyzed, including age, sex, BMI, baseline blood counts, baseline bone marrow blast percentage, previous history of VTE, use of antifibrinolytic agents, and whether blood products were transfused during the early treatment period. The variables of interest between VTE cases and non-VTE cases were compared using the nonparametric Wilcoxon rank sum test. RESULTSAcross the entire cohort (n=120), VTE developed in 25 patients (20.8%) and did not develop in 95 patients (79.2%). Table 1 and Table 2 show comparisons between VTE cases and patients without VTE for both quantitative and categorical variables. Median INR values at diagnosis and across the first 7 days of induction tended to be lower in patients with VTE and reached significance on days 3-5 (p=0.032 for INR-Day 3, p=0.046 for INR-Day 4, p=0.014 for INR-Day 5). Patients with VTE had a median BMI of 30, while patients without VTE had a median BMI of 28, which approached statistical significance (p=0.055). 8% of patients with VTE (2/25) had a history of VTE prior to the diagnosis of AML, while 3% without VTE (3/95) had a history of previous VTE (OR 2.7, p=0.281). Mutation in genes involved in DNA methylation also conferred an increased risk of VTE, with the association approaching statistical significance (p=0.083). There were no other variables that were significantly different between the two groups. CONCLUSIONSIn this cohort of patients with non-APL AML, there was a trend towards lower INR correlating with an increased incidence of VTE. Additionally, higher BMI, previous history of VTE, and mutation in DNA methylation genes were associated with increased incidence of VTE, though these trends did not reach statistical significance. The pathophysiology of VTE in this setting is likely complex and multifactorial. The shorter INR in those who developed VTE suggests a mechanism independent of the development of DIC, which is distinct from APL. The finding that obesity and personal history of VTE, both known risk factors for thrombosis, were associated with an increased incidence of VTE is also consistent with a non-DIC mechanism. Mutations in DNA methylation genes may have contributed to increased risk of VTE in this cohort; while this association is compelling, further studies with larger sample sizes are needed to confirm this finding. This study was limited by small sample size and missing data, especially regarding available data on coagulation tests. However, this analysis uncovers interesting associations that shed light on the pathophysiology of VTE in AML. More research is needed to further elucidate risk factors for VTE in order to provide optimal supportive care for this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pragmatic Evaluation of an Algorithm Using D-Dimer Adjusted to Clinical Probability in the Diagnosis of Pulmonary Embolism

BACKGROUNDDiagnosis of pulmonary embolism (PE) using clinical decision rules in combination with D-dimer (DD) values is a standard practice. The Wells score is the most commonly used rule, either in its original (3-category) or modified (2-category) versions, and in conjunction with a (DD) <500 ng/mL allows to exclude a PE in approximately 30% of patients. The recent PEGeD study (Kearon et al. 2019) concluded that a PE can be safely excluded by using a DD threshold adjusted to the clinical pre-test probability (C-PTP). In that study PE was excluded in patients with low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL In the present study we aimed to evaluate the performance of the PEGeD algorithm in daily practice. METHODSWe conducted a retrospective cohort study involving all adult patients who presented at London Health Sciences Centre or St. Joseph's Health Care Emergency Departments in London, Ontario, Canada between November 1, 2018 and December 31, 2020 with signs or symptoms suggestive of a pulmonary embolism and for whom a DD was ordered electronically. They were excluded if they did not have complete follow-up information for at least 90 days from the initial visit, they were pregnant, they were on long term anticoagulation for other indications, or had chest imaging prior to DD order. Using the electronic hospital chart, we extracted demographics, imaging results, and the Wells score with all its individual components. In our center, information about the Wells score and its components is routinely and prospectively collected when ordering DD. Since the PEGeD algorithm is not routinely used in our hospital, data of the C-PTP was utilized to determine which DD cut-off should be applied to the patient. Decision to perform imaging studies was taken by the ED physician at the time of assessment. The outcome of interest was the proportion of a PE or DVT at 90 days after the visit to the ED in patients with a low or intermediate C-PTP and who did not receive an initial diagnosis of PE and 99% confidence intervals (CI) were estimated using the Wilson's score method. RESULTSA total of 2769 patient charts were reviewed and 1070 were included (Table 1, Figure 1). Of the 1070 patients, 71 (7%) of patients had a pulmonary embolism on initial presentation to the emergency department. At 90 days of follow up none (99% CI 0, 0.84) of the 787 patients who had a low C-PTP or a moderate C-PTP score and a DD <1000 ng/mL or <500 ng/mL, respectively, were positive for a PE . This included 194 patients who had a low C-PTP and a DD level of 500-999 ng/mL and 26 patients who had an intermediate C-PTP and a DD level of <500 ng/mL. Notably, 8 (1.02%, 99% CI 0.42-2.43) PEs would have been missed using the PEGeD protocol when using DD cut-off levels of <1000 ng/mL in the low C-PTP group, or <500 ng/mL in the intermediate C-PTP. CONCLUSIONSIn this cohort we found that if the PEGeD algorithm had been used, it would have resulted in a low risk of VTE during follow up in patients without an initial diagnosis of PE and who had either a low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL. We also found it would have been associated with 194 (48%) less diagnostic imaging studies in the low C-PTP range and 2 (6%) less studies in the intermediate C-PTP range. Despite this, 1% of patients with PE (99% upper confidence limit 2.43%) would have been missed. This study is limited by its retrospective nature with an inherent risk of misclassification. Further studies are needed before recommending the use of this algorithm in clinical practice.Work CitedKearon, C., de Wit, K., Parpia, S., Schulman, S., Afilalo, M., Hirsch, A., Spencer, F. A., Sharma, S., D'Aragon, F., Deshaies, J.-F., Le Gal, G., Lazo-Langner, A., Wu, C., Rudd-Scott, L., Bates, S. M., & Julian, J. A. (2019). Diagnosis of Pulmonary Embolism with d -Dimer Adjusted to Clinical Probability. New England Journal of Medicine, 381(22), 2125-2134. https://doi.org/10.1056/NEJMoa1909159 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.