Clinical Venous Thromboembolism Research Articles

The effect of obligatory Padua prediction scoring in hospitalized medically ill patients: A retrospective cohort study.

Venous thromboembolism (VTE) is considered a preventable cause of mortality. The evidence for the benefit of VTE prophylaxis in acute medical patients is non-conclusive. Meta-analysis of RCTs failed to demonstrate reduction of all-cause mortality, while showing higher risk of bleeding. The Israeli Ministry of Health has instructed to assess all acute medical patients for the risk for VTE using the Padua Prediction Score, without mandating prophylaxis. To evaluate the effect of filling the Padua score on clinical outcomes and VTE prophylaxis rates. Retrospective Study was performed in Israel during the years 2014-2017. The participants were divided to Padua compliance vs non-compliance group. Primary outcome: 30-day mortality. Secondary outcomes: 90-day incidence of VTE and suspected major bleeding. A propensity-weighted logistic multiple regression was performed. 18,890 patients were included in the study. The fulfillment of the Padua score was associated with an increased use of VTE prophylaxis, OR 1.66 (95% CI 1.49-1.84). However, there was no reduction of mortality or VTE events, OR 1.13 (95% CI 0.97-1.31) and OR 1.22 (95% CI 0.79-1.8) respectively. Hospitalizations related to hemoglobin decrease were not statistically different between the two groups. Padua score for the assessment of VTE risk in medical wards was associated with higher administration of pharmacological prophylaxis without reduction in VTE or mortality rate. Its usage should be reassessed as a performance measure.

Circulating Tumor DNA and Risk of Venous Thromboembolism in Locally Advanced Rectal Cancer

Venous thromboembolism (VTE) is a common complication in cancer patients, which negatively affects treatment delivery and, consequently, prognosis. The pathophysiology of cancer-associated thrombosis (CAT) is extremely complex, relying on cytokine release in response to interactions between tumor cells and macrophages, thus leading to endothelial damage and activation of coagulation. Several risk factors may contribute to VTE risk, including tumor types, advanced stage, and anti-cancer treatments. Anti-angiogenic agents or combination of systemic chemotherapy and concomitant radiotherapy (CT-RT), for instance, are well-established risk factors across different malignancies. Colorectal cancer (CRC) is not listed as a high-risk VTE tumor according to pivotal risk assessment models, although retrospective studies showed a VTE rate of around 20%. Consequently, considering the high prevalence of the disease, VTE in CRC represents a main burden in terms of morbidity, increased healthcare costs, and mortality. Rectal cancer (RC) comprises approximately 30% of all CRC. The treatment of locally advanced disease (LARC) consists of a multimodal approach which includes chemotherapy, radiotherapy, and surgery. In the context of CRC management, circulating tumor DNA (ctDNA) is a fast-growing tool able to detect minimal residual disease, useful for improving patients' stratification and prognosis. Moreover, its determination at the time of diagnosis may represent a surrogate of tumor burden, potentially increasing the risk of VTE compared to ctDNA negative patients. Due to the paucity of prospective data of VTE in LARC, the aim of this analysis is to describe the rate of VTE and the potential association between ctDNA levels at baseline and VTE occurrence. We conducted a prospective observational study enrolling patients with LARC managed with neoadjuvant CT-RT (capecitabine 1650 mg/m2 concomitant with 50,4 Gy pelvic long course radiotherapy), surgery, plus/minus adjuvant chemotherapy at European Institute of Oncology (IEO) between November 2014 and November 2019. Blood samples for ctDNA were obtained at pre-planned timepoints: baseline (T0), end of CT-RT (T1), after surgery (T2), end of adjuvant chemotherapy (T3). ctDNA was extracted from plasma and mutations detected on tumor biopsy (KRAS, NRAS, BRAF, PIK3CA) were evaluated on ctDNA. Among other clinical information, VTE events were collected, including pulmonary embolism (PE), deep vein thrombosis (DVT) and visceral venous thrombosis (VVT). VTE was counted when occurred after or whitin 30 days before LARC diagnosis. The ctDNA value, defined as variant allele frequency (VAF) in a targeted mutation, was analyzed for correlation with clinical outcomes and VTE events. Median baseline ctDNA value was set as threshold to subdivide patients in VAF high and VAF low. We enrolled 111 patients. Sixty-one (55%) patients harboring tumoral tissue mutations underwent liquid biopsy. KRAS mutation was the most frequent one (42%), followed by NRAS (7%) and PIK3CA (5%). Fifty-one patients (83%) had a clinical node positive disease. Baseline Khorana Score (KS) was 0 in 54 patients (88%) and 1 in 7. Median ctDNA value at T0 was 0.11 ng/2ml (range: 0.00 - 17.40). After a median follow up of 82 months, 9 VTE events (15%) were diagnosed, 4 PE, 3 DVT and 2 VVT. The median time from diagnosis to VTE event was 14 months (IQR 6 - 51). VTE occurrence was associated with VAF high at baseline, even though not statistically significant (Hazard Ratio [HR]: 2.85; 95% CI: 0.71-11.4, p value = 0.14). Looking specifically at KRAS mutant patients, 6 VTE events were observed, all experienced by VAF high patients (HR not estimable, p value = 0.001). Considering the overall population, VTE rate was 14% and no statistical differences were observed for VTE development according to mutational profile. In our prospective study on LARC patients, VTE was associated with high levels of ctDNA at diagnosis, although not statistically significant. However, the association was significant in KRAS mutant tumors, which may represent a subset of patients with higher risk of thromboembolic complications. Prospective translational studies using deeper molecular techniques and wider populations are required to define the role of ctDNA as additional predictive tool to stratify VTE risk in cancer patients.

Extended Full Dose Versus Low Dose Direct Oral Anticoagulants in Cancer and Overweight Patients

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced-dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case-control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; p<0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21-1.80; p<0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p<0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6-4.9 months in non-cancer patients (Table 1). Non-cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non-cancer patients In comparing weight, ≥120kg to <120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer-specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Tranexamic acid is safe with respect to the risk of deep venous thrombosis in patients with hemophilic arthritis undergoing total knee arthroplasty without chemoprophylaxis: A prospective study

BackgroundPharmacologic thromboprophylaxis is controversial for hemophiliacs who undergo total joint replacements. The purpose of this study was to assess the safety of tranexamic acid (TXA) utilization with respect to the incidence of deep venous thrombosis (DVT) in hemophiliacs undergoing total knee arthroplasty (TKA). MethodsA total of 104 patients with hemophilic arthritis were included in the study. The patients were randomly divided into two groups of 52 subjects. All patients received a modified coagulation factor substitution regimen. In the TXA group, 1 g of TXA was injected intravenously 15 min before incision and 2 g of TXA was intra-articularly injected in the surgical area. A routine mechanical prophylaxis was administered to all patients under a standardized postoperative protocol. Thromboembolic complications in both groups were followed up for 2 years. ResultsAll patients were male and underwent 146 arthroplasties. There was a mean age of 33.2 ± 8.8 years and a mean body mass index of 22.2 ± 5.1 kg/m2. A 100% compliance rate was observed with mechanical prophylaxis. No asymptomatic DVT was detected on postoperative ultrasound in all patients. We also failed to find any proof of clinical venous thromboembolism in our patients during a 2-year follow up. Only two cases in the TXA group underwent blood transfusions (4.0%), while 29.2% of the patients in the non-TXA group needed transfusion. ConclusionsThis prospective study showed that TXA could be safely utilized in patients with hemophilic arthritis who underwent TKA without increasing the incidence of DVT and routine chemoprophylaxis may not be necessary.

Extended postoperative venous thromboembolism prophylaxis after bariatric surgery: a comparison of existing risk-stratification tools and 5-year MBSAQIP analysis.

Venous thromboembolism (VTE) is a leading cause of 30-day mortality after metabolic and bariatric surgery (MBS). Multiple predictive tools exist for VTE risk assessment and extended VTE chemoprophylaxis determination. To review existing risk-stratification tools and compare their predictive abilities. MBSAQIP database. Retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was performed (2015-2019) for primary minimally invasive MBS cases. VTE clinical factors and risk-assessment tools were evaluated: body mass index threshold of 50 kg/m2, Caprini risk-assessment model, and 3 bariatric-specific tools: the Cleveland Clinic VTE risk tool, the Michigan Bariatric Surgery Collaborative tool, and BariClot. MBS patients were deemed high risk based on criteria from each tool and further assessed for sensitivity, specificity, and positive predictive value. Overall, 709,304 patients were identified with a .37% VTE rate. Bariatric-specific tools included multiple predictors: procedure, age, race, gender, operative time, length of stay, heart failure, and dyspnea at rest; operative time was the only variable common to all. The body mass index cutoff and Caprini risk-assessment model had higher sensitivity but lower specificity when compared with the Michigan Bariatric Surgery Collaborative and BariClot tools. While the sensitivity of the tools varied widely and was overall low, the Cleveland Clinic tool had the highest sensitivity. The bariatric-specific tools would have recommended extended prophylaxis for 1.1%-15.6% of patients. Existing MBS VTE risk-assessment tools differ widely for inclusion variables, high-risk definition, and predictive performance. Further research and registry inclusion of all significant risk factors are needed to determine the optimal risk-stratified approach for predicting VTE events and determining the need for extended prophylaxis.

Predicting venous thromboembolism (VTE) risk in cancer patients using machine learning

AbstractBackgroundThe association between cancer and venous thromboembolism (VTE) is well‐established with cancer patients accounting for approximately 20% of all VTE incidents. In this paper, we have performed a comparison of machine learning (ML) methods to traditional clinical scoring models for predicting the occurrence of VTE in a cancer patient population, identified important features (clinical biomarkers) for ML model predictions, and examined how different approaches to reducing the number of features used in the model impact model performance.MethodsWe have developed an ML pipeline including three separate feature selection processes and applied it to routine patient care data from the electronic health records of 1910 cancer patients at the University of California Davis Medical Center.ResultsOur ML‐based prediction model achieved an area under the receiver operating characteristic curve of 0.778 ± 0.006 (mean ± SD) when trained on a set of 15 features. This result is comparable with the model performance when trained on all features in our feature pool [0.779 ± 0.006 (mean ± SD) with 29 features]. Our result surpasses the most validated clinical scoring system for VTE risk assessment in cancer patients by 16.1%. We additionally found cancer stage information to be a useful predictor after all performed feature selection processes despite not being used in existing score‐based approaches.ConclusionFrom these findings, we observe that ML can offer new insights and a significant improvement over the most validated clinical VTE risk scoring systems in cancer patients. The results of this study also allowed us to draw insight into our feature pool and identify the features that could have the most utility in the context of developing an efficient ML classifier. While a model trained on our entire feature pool of 29 features significantly outperformed the traditionally used clinical scoring system, we were able to achieve an equivalent performance using a subset of only 15 features through strategic feature selection methods. These results are encouraging for potential applications of ML to predicting cancer‐associated VTE in clinical settings such as in bedside decision support systems where feature availability may be limited.

#5401 REAL-WORLD STUDY BETWEEN NEPHROTIC SYNDROME AND VENOUS THROMBOEMBOLISM

Abstract Background and Aims Nephrotic syndrome (NS) is a recognized risk factor of venous thromboembolism (VTE), however, there have been limited comprehensive epidemiologic data on VTE among NS patients. Therefore, we designed our study to assess the epidemiology and clinical correlates of VTE among hospitalized adults with NS in China. Method In this nationwide real-world study of 78,797 hospitalized patients with NS from 18 medical centers across China, VTE was identified by International Classification of Diseases, 10th revision (ICD-10) codes or imagological examinations during hospitalization. Multivariable logistic regression analysis was used to investigate the association between clinical variables and VTE through the R Programming software. Results A total of 1227 VTE cases were identified in the hospitalized NS population and the detection rate was 1.56%. Detection rate of VTE varied significantly in patients with different pathologic types of NS. Patients with membranous nephropathy (MN) had a significantly increased risk of VTE {Odds ratio [OR] 2.11 [95% confidence interval (CI) 1.12–4.36]}. While patients with focal segmental glomerulosclerosis (FSGS) did not show a significant high risk [OR 0.93 (95% CI 0.29–2.60)] compared with minimal change disease. We also found that male [OR 1.44 (95% CI 1.15–1.80)], age [OR 1.09 (95% CI 1.02–1.17)], anemia [OR 1.50 (95% CI 1.15–1.95)], cerebral bleeding [OR 3.23 (95% CI 1.69–6.16)], respiratory tract infection [OR 2.05 (95% CI 1.60–2.63)], respiratory failure [OR 2.24 (95% CI 1.42–3.53)], use of proton pump inhibitors (PPIs) [OR 2.19 (95% CI 1.54–3.12)], use of glucocorticoids [OR 1.46 (95% CI 1.03–2.09)] and immunosuppressants [OR 1.48 (95% CI 1.14–1.93), orthopedic operations [OR 1.97 (95% CI 1.22–3.18)], high-level D-dimer (>0.55 mg/L) [OR 2.62 (95% CI 1.87–3.65)] were associated with increased risk of VTE detection. While 24-hour urine protein quantification >10 g/d [OR 1.24 (95% CI 0.90–1.70)] showed little significant correlation with VTE. Hypertension [OR 0.74 (95% CI 0.58–0.95)] and the use of diuretics [OR 0.72 (95% CI 0.53–0.97)] were found to have a negative correlation with VTE detection. Conclusion The detection rate of VTE among patients with NS during hospitalization was 1.56%. Male, age, MN, anemia, cerebral bleeding, respiratory tract infection, respiratory failure, and use of PPIs, glucocorticoids and immunosuppressants, high D-dimer concentration were associated with VTE detection in NS. While 24-hour proteinuria did not show a significant association with VTE identification.

External validation of a novel electronic risk score for cancer-associated thrombosis in a comprehensive cancer center.

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 [95% CI 0.69-0.72] with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 [95% CI 0.62-0.65]. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.

Postoperative Timing of Chemoprophylaxis and Its Impact on Thromboembolism and Bleeding Following Major Abdominal Surgery: A Multicenter Cohort Study

BackgroundMajor abdominal surgery is associated with bleeding and venous thromboembolism (VTE) risks. Chemoprophylaxis prevents VTE but increases bleeding risk. When compared with pre- and intra-operative chemoprophylaxis, recent evidence suggests that starting chemoprophylaxis postoperatively lowers the risk of bleeding without compromising VTE protection. This study investigates whether an optimal window exists in the postoperative period for initiating chemoprophylaxis in patients undergoing major abdominal surgery.MethodsAnalysis of pooled data from four multicenter PROTECTinG studies, which investigated the timing of perioperative chemoprophylaxis on bleeding and VTE outcomes following major abdominal surgery. Patients that commenced chemoprophylaxis postoperatively were separated into quartiles based on timing of administration within the first 24 h post-surgery.ResultsOverall, 4729 (Abdominal visceral resection N = 668, cholecystectomies N = 573, major ventral hernia repair N = 1701, antireflux surgery N = 1787) consecutive patients had chemoprophylaxis commenced within 24 h following elective surgery. Baseline characteristics were comparable between quartiles. Across quartiles and within each procedural type, the timing of starting chemoprophylaxis was not associated with bleeding (2.6, 1.7, 2.7 and 3.2%, p = 0.130) or clinical VTE (0.8, 0.2, 0.8 and 0.5%, p = 0.131), and did not predict their occurrences on multivariate analysis. ConclusionChemoprophylaxis can be safely started at any time within 24 h post-skin closure in major abdominal surgery, without affecting bleeding or VTE risks. This finding encourages the standardization of chemoprophylaxis timing in the postoperative period to pre-defined times during the day to improve workflow efficiency and chemoprophylaxis compliance.

Venous thromboembolism in viral diseases: A comprehensive literature review.

Venous thromboembolism (VTE) is known to be a common respiratory and/or cardiovascular complication in hospitalized patients with viral infections. Numerous studies have proven human immunodeficiency virus infection to be a prothrombotic condition. An elevated VTE risk has been observed in critically ill H1N1 influenza patients. VTE risk is remarkably higher in patients infected with the Hepatitis C virus in contrast to uninfected subjects. The elevation of D-dimer levels supported the association between Chikungunya and the Zika virus and the rise of clinical VTE risk. Varicella-zoster virus is a risk factor for both cellulitis and the consequent invasive bacterial disease which may take part in thrombotic initiation. Eventually, hospitalized patients infected with the coronavirus disease of 2019 (COVID-19), the cause of the ongoing worldwide pandemic, could mainly suffer from an anomalous risk of coagulation activation with enhanced venous thrombosis events and poor quality clinical course. Although the risk of VTE in nonhospitalized COVID-19 patients is not known yet, there are a large number of guidelines and studies on thromboprophylaxis administration for COVID-19 cases. This study aims to take a detailed look at the effect of viral diseases on VTE, the epidemiology of VTE in viral diseases, and the diagnosis and treatment of VTE.

Development and validation of machine learning models for postoperative venous thromboembolism prediction in colorectal cancer inpatients: a retrospective study.

Colorectal cancer (CRC) is a heterogeneous group of malignancies distinguished by distinct clinical features. The association of these features with venous thromboembolism (VTE) is yet to be clarified. Machine learning (ML) models are well suited to improve VTE prediction in CRC due to their ability to receive the characteristics of a large number of features and understand the dataset to obtain implicit correlations. Data were extracted from 4,914 patients with colorectal cancer between August 2019 and August 2022, and 1,191 patients who underwent surgery on the primary tumor site with curative intent were included. The variables analyzed included patient-level factors, cancer-level factors, and laboratory test results. Model training was conducted on 30% of the dataset using a ten-fold cross-validation method and model validation was performed using the total dataset. The primary outcome was VTE occurrence in postoperative 30 days. Six ML algorithms, including logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), weighted support vector machine (SVM), a multilayer perception (MLP) network, and a long short-term memory (LSTM) network, were applied for model fitting. The model evaluation was based on six indicators, including receiver operating characteristic curve-area under the curve (ROC-AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Brier score. Two previous VTE models (Caprini and Khorana) were used as the benchmarks. The incidence of postoperative VTE was 10.8%. The top ten significant predictors included lymph node metastasis, C-reactive protein, tumor grade, anemia, primary tumor location, sex, age, D-dimer level, thrombin time, and tumor stage. In our results, the XGBoost model showed the best performance, with a ROC-AUC of 0.990, a SEN of 96.9%, a SPE of 96.1% in training dataset and a ROC-AUC of 0.908, a SEN of 77.5%, a SPE of 93.7% in validation dataset. All ML models outperformed the previously developed models (Caprini and Khorana). This study developed postoperative VTE predictive models using six ML algorithms. The XGBoost VTE model might supply a complementary tool for clinical VTE prophylaxis decision-making and the proposed risk factors could shed some light on VTE risk stratification in CRC patients.

Profile of Solid Tumor Patients Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study Based on 1482 Cases

The aim of this single-centre 10-year retrospective observational study was to evaluate the profile of Chinese cancerous patients complicated with venous thromboembolism (VTE) based on demographic features, clinical characteristics, and medication exposure. Consecutive 1482 patients with solid tumor complicated with VTE at a tertiary center between 2012 and 2021 were retrospectively enrolled. Data were collected on demographics, comorbidities, discharge diagnoses, laboratory examination data, treatment details, and imaging description of the lesion. The overall incidence of clinical VTE was 1.35% in hospitalized patients with cancer in our center. Lung cancer was the most frequent tumor subtype for developing VTE events, accounting for 24.83% of all cases. Over half of the patients (66.60%) were observed to have an increased risk of VTE within the first 6 months of cancer diagnosis. Close to half of the patients (46.49%) had received chemotherapy within 6 months prior to the diagnosis of VTE. The frequency of massive ascites group (＞2000 mL) in gynecological patients with VTE was significantly larger than that of nonmassive ascites group (≤2000 mL) (P < .001). Patients with ovarian, vulvar, lung cancers were considered at high risk for VTE. The assessment and monitoring of VTE in patients with cancer within the first 6 months of cancer diagnosis should be strengthened. VTE occurrence was closely related to advanced age and stage, adenocarcinoma, obesity and noval anticancer therapies in patients with cancer. Early detection of VTE-related examination may lead to earlier intervention for patients with gynecological tumors with preoperative massive ascites.

Optimal Timing of Perioperative Chemoprophylaxis in Patients With High Thromboembolic Risk Undergoing Major Abdominal Surgery: A Multicenter Cohort Study.

To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population. Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown. Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score >4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or >20g/L fall in hemoglobin. From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60-2.15, P =0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52-2.73, P <0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40-2.81, P <0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32-3.35, P =0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25-2.34, P <0.001), but not VTE. In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk.

Development of a risk assessment scale and test of its validity and reliability for venous thromboembolism in adult burn patients

Development of a risk assessment scale and test of its validity and reliability for venous thromboembolism in adult burn patients

Early Versus Postoperative Chemical Thromboprophylaxis Is Associated with Increased Bleeding Risk Following Abdominal Visceral Resections: a Multicenter Cohort Study

BackgroundAbdominal visceral resections incur relatively higher rates of postoperative bleeding and venous thromboembolism (VTE). While guidelines recommend the use of perioperative chemical thromboprophylaxis, the most appropriate time for its initiation is unknown. Here, we investigated whether early (before skin closure) versus postoperative commencement of chemoprophylaxis affected VTE and bleeding rates following abdominal visceral resection. MethodsRetrospective review of all elective abdominal visceral resections undertaken between January 1, 2018, and June 30, 2019, across four tertiary-referral hospitals. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin from baseline. Clinical VTE was defined as imaging-proven symptomatic disease < 30 days post-surgery. ResultsA total of 945 cases were analyzed. Chemoprophylaxis was given early in 265 (28.0%) patients and postoperatively in 680 (72.0%) patients. Mean chemoprophylaxis exposure doses were similar between the two groups. Clinical VTE developed in 14 (1.5%) patients and was unrelated to chemoprophylaxis timing. Postoperative bleeding occurred in 71 (7.5%) patients, with 57 (80.3%) major bleeds, requiring blood transfusion in 48 (67.6%) cases and reintervention in 31 (43.7%) cases. Bleeding extended length-of-stay (median (IQR), 12 (7–27) versus 7 (5–11) days, p < 0.001). Importantly, compared to postoperative chemoprophylaxis, early administration significantly increased the risk of bleeding (10.6% versus 6.3%, RR 1.45, 95% CI 1.05–1.93, p = 0.038) and independently predicted its occurrence. ConclusionsThe risk of bleeding following elective abdominal visceral resections is substantial and is higher than the risk of clinical VTE. Compared with early chemoprophylaxis, postoperative initiation reduces bleeding risk without an increased risk of clinical VTE.

Chemical thromboprophylaxis before skin closure increases bleeding risk after major ventral hernia repair: A multicenter cohort study

BackgroundMajor ventral hernia surgeries are commonly performed. Despite guideline recommendations for chemo-thromboprophylaxis in the perioperative period, the optimal timing for its initiation is unknown. We characterized the variability in perioperative chemoprophylaxis in elective major ventral hernia surgery and determine whether timing of chemoprophylaxis affects bleeding and symptomatic venous thromboembolism. MethodsRetrospective analysis of all elective major ventral hernia surgery undertaken between January 1, 2014, and December 31, 2019, at 14 hospitals across Australia. Major bleeding was defined as the need for blood transfusion, reoperation, or >20 g/L fall in hemoglobin. Clinical venous thromboembolism was defined as imaging-proven symptomatic disease <30 days postsurgery. Propensity score matched analysis was used to validate primary findings. ResultsIn the study, 3,384 hernia repairs were analyzed. Chemoprophylaxis was administered early (before skin closure), postoperatively, or not given in 856 (25.3%), 1,701 (50.3%), and 827 (24.4%) patients, respectively. This varied between surgeons, trainees, and institutions. Clinical venous thromboembolism occurred in 6 (0.2%) patients and was unrelated to chemoprophylaxis timing. 134 (4.0%) patients had postoperative bleeding, with 67 (50%) major bleeds, requiring surgical control in 41 (30.6%) cases. Bleeding extended duration of stay (mean [standard deviation], 7.0 (13.9) vs 2.6 (4.7) days, P < .001). Notably, compared with postoperative (odds ratio 1.98; 95% confidence interval, 1.36–2.88; P < .001) and no (odds ratio 2.83; 95% confidence interval, 1.70–4.89; P < .001) chemoprophylaxis, early initiation significantly increased bleeding risk and independently predicted its occurrence. ConclusionThe incidence of clinical venous thromboembolism after elective major ventral hernia repair is low. Variability in perioperative thromboprophylaxis is high. Early chemoprophylaxis increases bleeding risk without appreciable additional protection from venous thromboembolism.

Randomised comparative effectiveness trial of Pulmonary Embolism Prevention after hiP and kneE Replacement (PEPPER): the PEPPER trial protocol

IntroductionMore than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%–0.5% fatal PE, and over 1000...

Clinical venous thromboembolism in spinal trauma with and without spinal cord injury: A 3-year experience of midlands centre for spinal injuries, Oswestry, UK

Clinical venous thromboembolism in spinal trauma with and without spinal cord injury: A 3-year experience of midlands centre for spinal injuries, Oswestry, UK

Prevalence, Patterns, and Predictors of Venous Thromboembolic Events in Patients Undergoing Salvage Chemotherapy and Autologous Stem Cell Transplantation for Relapsed Lymphomas.

Almost 25% of patients with lymphoma may have relapse or develop refractory disease, and a majority of such patients undergo salvage chemotherapy and autologous stem cell transplantation (ASCT). Data on venous thromboembolism (VTE) in this setting are scarce. This study aimed to investigate the prevalence and factors that may increase the risk of VTE in such patients. Adult patients who were diagnosed with lymphoma and received salvage chemotherapy and ASCT were included in the study, and the subgroup with radiologically confirmed VTE were identified. Correlations between different clinical and laboratory variables and VTE were evaluated. A total of 216 patients (median age, 31 [range, 19-60] years) were enrolled in the study. Most patients (n = 140, 64.8%) had Hodgkin's lymphoma, while 54 (25.0%) had diffuse large B-cell lymphoma. A total of 36 (16.7%) patients had VTE, mostly as upper extremity deep vein thrombosis (n = 28, 77.8%); 18 (50%) of the cases were related to central venous catheter insertion. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) level (29.2% vs. 5.9%, p < 0.001), those with mediastinal involvement (25.9% vs. 11.5%, p = 0.025). and those with longer hospital stay (22.3% vs.9.5%, p = 0.036). In the multivariate analysis, high LDH level (odds ratio (OR), 6.53; p < 0.001), mediastinal involvement (OR, 2.70; p = 0.005) and hospital stay ≥24 days (OR, 2.71; p = 0.007) were all associated with significantly higher VTE rates. Patients with relapsed lymphoma undergoing salvage chemotherapy and ASCT are at higher risk for VTE, especially in those with high LDH level, mediastinal involvement, and prolonged hospital stay. If no contraindications exist, thromboprophylaxis might be considered in these settings.

Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown.Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation.Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis.Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02).Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.