Venous Thromboembolism Risk Stratification Research Articles

Higher incidence of venous thromboembolism associated with increasing lines of treatment in heavily treated ovarian cancer patients

ObjectiveOvarian cancer is associated with a high rate of venous thromboembolism. Our objective is to report the incidence of venous thromboembolism in recurrent ovarian cancer, assess the impact on morbidity...

Risk Assessment Models for Venous Thromboembolism in Medical Inpatients

Thromboprophylaxis is recommended for medical inpatients at risk of venous thromboembolism (VTE). Risk assessment models (RAMs) have been developed to stratify VTE risk, but a prospective head-to-head comparison of validated RAMs is lacking. To prospectively validate an easy-to-use RAM, the simplified Geneva score, and compare its prognostic performance with previously validated RAMs. This prospective cohort study was conducted from June 18, 2020, to January 4, 2022, with a 90-day follow-up. A total of 4205 consecutive adults admitted to the general internal medicine departments of 3 Swiss university hospitals for hospitalization for more than 24 hours due to acute illness were screened for eligibility; 1352 without therapeutic anticoagulation were included. At admission, items of 4 RAMs (ie, the simplified and original Geneva score, the Padua score, and the IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score) were collected. Patients were stratified into high and low VTE risk groups according to each RAM. Symptomatic VTE within 90 days. Of 1352 medical inpatients (median age, 67 years [IQR, 54-77 years]; 762 men [55.4%]), 28 (2.1%) experienced VTE. Based on the simplified Geneva score, 854 patients (63.2%) were classified as high risk, with a 90-day VTE risk of 2.6% (n = 22; 95% CI, 1.7%-3.9%), and 498 patients (36.8%) were classified as low risk, with a 90-day VTE risk of 1.2% (n = 6; 95% CI, 0.6%-2.6%). Sensitivity of the simplified Geneva score was 78.6% (95% CI, 60.5%-89.8%) and specificity was 37.2% (95% CI, 34.6%-39.8%); the positive likelihood ratio of the simplified Geneva score was 1.25 (95% CI, 1.03-1.52) and the negative likelihood ratio was 0.58 (95% CI, 0.28-1.18). In head-to-head comparisons, sensitivity was highest for the original Geneva score (82.1%; 95% CI, 64.4%-92.1%), while specificity was highest for the IMPROVE score (70.4%; 95% CI, 67.9%-72.8%). After adjusting the VTE risk for thromboprophylaxis use and site, there was no significant difference between the high-risk and low-risk groups based on the simplified Geneva score (subhazard ratio, 2.04 [95% CI, 0.83-5.05]; P = .12) and other RAMs. Discriminative performance was poor for all RAMs, with an area under the receiver operating characteristic curve ranging from 53.8% (95% CI, 51.1%-56.5%) for the original Geneva score to 58.1% (95% CI, 55.4%-60.7%) for the simplified Geneva score. This head-to-head comparison of validated RAMs found suboptimal accuracy and prognostic performance of the simplified Geneva score and other RAMs to predict hospital-acquired VTE in medical inpatients. Clinical usefulness of existing RAMs is questionable, highlighting the need for more accurate VTE prediction strategies.

Comparison of the PADUA and IMPROVE scores in assessing venous thromboembolism risk in 42,257 medical inpatients in China.

Venous thromboembolism (VTE) is a major contributor to hospital mortality and disability-adjusted life-year (DALY) loss. Multiple guidelines recommend using the Padua or IMPROVE scores to stratify VTE risk in hospitalized medical patients. However, the IMPROVE score is not recommended in Chinese guidelines, and there is very little evaluation of its clinical application and effectiveness in the Chinese population. The objective of this study is to compare the efficacy of the Padua and IMPROVE scoring models for assessing VTE risk in Chinese medical inpatients. We conducted a retrospective analysis of the clinical characteristics and thrombotic risk of 42,257 medical inpatients at a tertiary hospital in Guangdong, China, between 2021 and 2022. Logistic regression was used to assess thrombotic risk factors. The Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC), sensitivity, and specificity were employed to evaluate the performance of the two models. Of the 42,257 patients included, 948 (2.24%) experienced VTE during hospitalization. According to the Padua score, 3,7513 (88.78%) of patients were considered low risk, while 4,744 (18.22%) were classified as high risk. The IMPROVE score identified 20,744 (49.09%) of patients as low risk, 20799(49.22%) as intermediate risk, and 714(1.69%) as high risk. The AUC for the Padua score was 0.735 (95% CI: 0.717-0.753), with a sensitivity of 49.4% and specificity of 89.6%. For the IMPROVE score, the AUC was 0.711 (95% CI: 0.693-0.729), with a sensitivity of 32.5% and specificity of 99.0%. The DeLong test, used to compare the AUCs, yielded a z-value of 1.886 with a P-value of 0.059, indicating no statistical difference. When assessing VTE risk in patients with stroke, cancer, nephrotic syndrome, and critical illness (ICU/CCU stay), both scoring models showed comparable predictive performance with AUCs ranging between 0.7 and 0.8. Both the Padua score and IMPROVE score have good predictive ability for VTE events during hospitalization in medical patients. Among them, the IMPROVE score has objective assessment items, simpler operation, and more detailed risk stratification, which is beneficial for clinicians to take physical and pharmacological preventive measures at different levels.ChiCTR2200056903, February 22, retrospectively registered.

Inaccuracy of Initial Clinical Mobility Assessment in Venous Thromboembolism Risk Stratification

BackgroundVenous thromboembolism risk increases in hospitals due to reduced patient mobility. However, initial mobility evaluations for thromboembolism risk are often subjective and lack standardization, potentially leading to inaccurate risk assessments and insufficient prevention. MethodsA retrospective study at a quaternary academic hospital analyzed patients using the Padua risk tool, which includes a mobility question, and the Johns Hopkins-Highest Level of Mobility (JH-HLM) scores to objectively measure mobility. Reduced mobility was defined as JH-HLM scores ≤3 over ≥3 consecutive days. The study evaluated the association between reduced mobility and hospital-acquired venous thromboembolism using multivariable logistic regression, comparing admitting health care professional assessments with JH-HLM scores. Symptomatic, hospital-acquired thromboembolisms were diagnosed radiographically by treating providers. ResultsOf 1715 patients, 33 (1.9%) developed venous thromboembolism. Reduced mobility, as determined by the JH-HLM scores, showed a significant association with thromboembolic events (adjusted OR: 2.53, 95%CI:1.23-5.22, P = .012). In contrast, the initial Padua assessment of expected reduced mobility at admission did not. The JH-HLM identified 19.1% of patients as having reduced mobility versus 6.5% by admitting health care professionals, suggesting 37 high-risk patients were misclassified as low risk and were not prescribed thrombosis prophylaxis; 4 patients developed thromboembolic events. JH-HLM detected reduced mobility in 36% of thromboembolic cases, compared to 9% by admitting health care professionals. ConclusionInitial mobility evaluations by admitting health care professionals during venous thromboembolism risk assessment may not reflect patient mobility over their hospital stay. This highlights the need for objective measures like JH-HLM in risk assessments to improve accuracy and potentially reduce thromboembolism incidents.

The Association of Anticoagulation Intensity with Outcomes in Hospitalized COVID-19 Patients.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease-19 (COVID-19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients' initial D-dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard-dose prophylaxis, high-dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID-19 patients hospitalized initially on the general inpatient wards between March 1,, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard-dose prophylaxis; 32 patients (3.5%) received high-dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in-hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high-dose prophylaxis group, there was a trend towards increased in-hospital mortality (odds ratio 2.4 (0.8-7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9-5.7, 95% CI)). Our results suggest that patients receiving high-dose prophylaxis had more severe disease that was not mitigated by intermediate-dose anticoagulation.

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.

Risk factors for venous thromboembolism in patients with pneumonia in the pre-COVID-19 era: a meta-analysis and systematic review.

Elevated risk of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) pneumonia has been recognized, while the risk factors associated with VTE in patients with non-COVID-19 pneumonia remain to be defined. This study aimed to conduct a meta-analysis and systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify potential risk factors for VTE in patients with pneumonia from the pre-COVID-19 era. PubMed, EMBASE, and Cochrane Library were searched. Two reviewers performed screening, full-text review, and extraction. Risk factors and odds ratio (OR) were estimated. Of 595 articles identified, six studies were included. Pooled analysis suggested that age ≥60 years [OR =2.75, 95% confidence interval (CI): 2.55-2.97, P<0.001], mechanical ventilation (MV) (OR =9.48, 95% CI: 8.24-10.91, P<0.001), hypertension (OR =1.41, 95% CI: 1.09-1.83, P=0.010), diabetes (OR =1.49, 95% CI: 1.36-1.64, P<0.001), heart failure (OR =3.15, 95% CI: 1.05-9.41, P=0.040) and cancer (OR =2.86, 95% CI: 2.07-3.95, P<0.001) were associated with higher risk for deep vein thrombosis in patients with pneumonia. While age ≥60 years (OR =2.46, 95% CI: 2.21-2.73, P<0.001), bacterial pneumonia (OR =3.80, 95% CI: 1.65-8.73, P=0.002), hyperlipidemia (OR =1.55, 95% CI: 1.00-2.41, P=0.049), heart failure (OR =2.70, 95% CI: 2.05-3.56, P<0.001), chronic obstructive pulmonary disease (OR =4.73, 95% CI: 3.11-7.17, P<0.001) and cancer (OR =2.90, 95% CI: 2.39-3.53, P<0.001) were risk factors for pulmonary embolism in patients with pneumonia. Patients with non-COVID-19 pneumonia, particularly those with advanced age, MV, cardiovascular comorbidities or cancer, warrant individualized management during hospitalization. Our findings could contribute to refining risk prediction models and further risk stratification for VTE in patients with pneumonia in clinical practice.

CDKN2C Deletion on 1p32 Locus As Part of Irwazh Score, a New Risk Assessment Model for Venous Thromboembolism Occurring within 6-12 Months of Treatment Initiation in Newly Diagnosed Multiple Myeloma

Background Adequate risk-stratification of venous thromboembolism (VTE) in multiple myeloma (MM) is an unmet need. Methods This is a retrospective study of 320 newly diagnosed MM (NDMM) patients treated from 2011 to 2023. All gave their informed consent. Required minimal follow-up (FU) length was 12 months or lower if VTE or death occurred. We aimed to evaluate VTE incidence at 6 and 12 months of first line treatment (L1) initiation, identify risk predictors and assess VTE impact on overall survival (OS). Comorbidities, baseline demographic (excluding race), clinical, biological (including FISH) and imaging data, treatment exposures, response profile and OS were all analyzed. Total scores for 4 existing risk assessment models (RAM) (IMPEDE-VTE, SAVED, PRISM, IFM/DFCI-related) were also calculated from L1 start. VTE events (VTEe) were adjudicated to exclude superficial ones and restrict analysis to documented deep vein thrombosis (DVT) and pulmonary embolism (PE). Predictors validated by Cox model were weighted based on their hazard ratios (HR). Results The cohort comprised 147 (45.9%) women and 111 (34.7%) transplant-eligible patients. Overall median age was 70.1 (36.6-98.4) years and 205 (64.1%) subjects were &amp;gt;65. Two hundred and twenty-five (70.3%) received standard-of-care regimens containing immunomodulatory drugs (IMID) (Thalidomide in 98: 30.6%; Revlimid in 127: 39.7%), while 130 (40.6%) received high-dose (≥160 mg) Dexamethasone (HDD) per L1 cycle. VTE prophylaxis was omitted in 32 (10%) or consisted of NSAID in 97 (30.3%), prophylactic low molecular weight heparin (LMWHp) in 115 (36%) and direct oral anticoagulant (DOA) in 55 (17.2%), while 10 (3.1%), 9 (2.8%) and 2 (0.6%) were previously receiving curative LMWH (LMWHc), vitamin K antagonist (VKA) or a mixed regimen, respectively, for prior VTE or other indications. In 33 (10.3%) patients, 34 VTEe occurred (31 [91.2%] within the first 6 months): 4 (11.8%) as both PE and DVT; 3 (8.8%) as PE; 27 (79.4%) as isolated proximal (12 [35.3%]) or distal (15 [44.1%]) DVT of the upper (2 [5.9%]) or lower (25 [73.5%]) limbs, including 3 (8.8%) with both proximal and distal and 3 (8.8%) close to central venous catheter. Based on Cox univariate analysis, VTEe were not related to usual parameters such as past VTE history, IMID, HDD or EPO exposure, prophylaxis omission or modality or recent surgery. A 6-parameter RAM, named Irwazh score, was built from multivariate Cox model, including: age &amp;lt;55 years (HR 0.34; 95% confidence interval [CI]: 0.0-0.8; p=0.014), prior diabetes (HR 3.41; 95% CI: 1.48-7.85; p=0.004), creatinine clearance (Cr-Cl) using MDRD &amp;lt;40 ml/mn (HR 2.64; 95% CI: 1.26-5.51; p=0.009), CRP ≥10 mg/dl (HR 2.65; 95% CI: 1.27-5.48; p=0.009), ≥50% 1p32 deletion (HR 3.44; 95% CI: 1.17-10.09; p=0.024) and minimal response (MR) to L1 (HR 4.67; 95% CI: 1.71-12.73; p=0.003). Area under the curve (AUC) was 0.718 (95% CI: 0.624-0.811; p&amp;lt;0.0001) at 12 months and 0.731 (95% CI: 0.636-0.825; p&amp;lt;0.0001) at 6. In comparison, AUC was 0.649 (95% CI: 0.546-0.751; p=0.004) for IMPEDE-VTE, 0.597 (95% CI: 0.505-0.689; p=0.039) for PRISM, 0.584 (95% CI: 0.486-0.682: p=0.091) for IFM/DFCI-related and 0.580 (95% CI: 0.473-0.687; p=0.141) for SAVED (Figure 1). Based on points attributed to each parameter (age &amp;lt;55 years: 1; prior diabetes: 9; Cr-Cl&amp;lt;40 ml/mn: 6; CRP≥10 mg/dl: 6; ≥50% 1p32 deletion: 9; MR: 11), patients were stratified into low (&amp;lt;6 points), intermediate (6-15) and high risk (≥16), with 12-month cumulative VTE incidence of 4,51% (6/133), 10,45% (16/153) and 35,29% (12/34), respectively. Of low-risk patients, 2 were receiving NSAID and 4 LMWHp; of intermediate-risk ones, 2 had no prophylaxis, 9 were under NSAID and 5 LMWHp; of high-risk ones, 2 had no prophylaxis, 5 were receiving NSAID, 2 LMWHp, 1 VKA, 1 LMWHc and 1 DOA. Using Kaplan-Meier analysis for VTE-free survival, statistical difference was found significant between low- and intermediate-risk ( p=0.043), low- and high-risk ( p&amp;lt;0.0001) and intermediate- and high-risk groups ( p=0.000) (Figure 2). Median total FU was 33.2 (0.2-147) months; OS assessment using Cox model did not find a significant statistical impact of VTE neither at 6 ( p=0.491) and 12 ( p=0.199) months nor during the whole FU length ( p=0.438). Conclusion The Irwazh score, with an unprecedented FISH feature, a statistically significant risk-stratifying power and a better AUC than existing VTE RAMs is worth validating in a larger clinical study.

Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Patients with cancer have an increased risk of venous thromboembolism (VTE). Currently, several VTE risk prediction tools have been developed to identify candidates for primary VTE thromboprophylaxis. However, the availability of reliable and highly discriminatory prediction models for VTE risk assessment in cancer patients is limited, warranting further improvement of VTE risk stratification strategies. The implementation of biomarkers in risk assessment models might lead to refined VTE risk prediction, but it remains to be more comprehensively investigated. In this systematic review and meta-analysis, we aimed to evaluate and summarize all candidate biomarkers and their association with cancer-associated VTE. We conducted an electronic search in Medline, EMBASE and Cochrane central databases for studies that evaluated biomarkers in adult patients with cancer from inception to September 26 th 2022. We included observational and interventional studies reporting on subsequent VTE occurring after a cancer diagnosis. The baseline or index event of the biomarker measurements had to be definitively and uniformly applied to all enrolled patients. Two reviewers independently screened titles, abstracts and full-text articles for inclusion. Median differences (for continuous measures) and Odds Ratios (OR) (for dichotomous cut-off measures) with 95% confidence intervals (95% CI) were estimated and pooled using random-effects models. We assessed each studies risk of bias using the Quality in Prognostic Studies (QUIPS) risk of bias tool. Our search identified 4274 studies that were screened for inclusion (Figure 1). Following the screening, 109 studies (with 520 biomarker measurements) met the inclusion criteria and were included in the systematic review. Of these, 51 studies (with 174 biomarker measurements) were included in the meta-analysis. The majority of the studies were cohort studies (n=47; 32 prospective and 15 retrospective), while the other 4 studies were nested case-control studies. Eighteen studies had a study population of mixed cancer types and the remaining studies had a study population of specific cancer types, including: lung (n=6), gynecologic (n=5), breast (n=3), stomach (n=3), lymphoma (n=2), myeloma (n=2), ovarian (n=2), pancreas (n=2), brain (n=1), colorectal (n=1), gastrointestinal (n=1), genitourinary (n=1), gynecologic or breast (n=1), head and neck (n=1), liver (n=1), and prostate (n=1). We calculated the median difference and 95% CI for 23 different biomarkers. Cancer patients who experienced subsequent VTE events had significantly higher pre-treatment factor VIII activity, peak thrombin, platelet count and prothrombin fragment F1+2 levels compared to patients who did not experience VTE events (Table 1). Pre-treatment d-dimer levels were also higher in cancer patients who developed VTE, however, considerable heterogeneity was observed (Table 1). Contrastingly, pre-treatment hemoglobin, lag time - thrombin generation, prothrombin time and time to peak thrombin levels were significantly lower in those experiencing VTE events compared to patients who did not experience any events (Table 1). D-dimer levels on day-1 after cancer surgery were reported in two studies which, when pooled, revealed that cancer patients with subsequent VTE had higher d-dimer levels post-operatively compared to those with no events (Table 1). Moreover, pre-treatment hemoglobin levels 100 g/L was significantly associated with future VTE risk [OR: 1.42 (95%CI: 1.03-1.97), I 2=0%, n=11] while neutrophil lymphocyte ratio 3 was associated, yet insignificant [OR: 1.60 (95%CI: 0.99-2.60), I 2=43%, n=4]. Pre-treatment platelet count 350 x 10 9/L and white blood count levels 11 x 10 9/L were not significantly associated with future VTE risk [OR: 0.84 (95%CI: 0.66-1.06), I 2=0%, n=9 and 1.32 (0.86-2.03), I 2=56%, n=8, respectively]. From the 51 studies included in the meta-analyses, 27 studies had a low risk of bias, 19 studies had a moderate risk of bias and 5 studies had a high risk of bias. In conclusion, nine blood biomarkers were found to be significantly associated with VTE in cancer patients. Their utility as predictors of VTE in thrombotic risk assessment models may help in optimising VTE prediction and should be further explored in future studies.

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.

Inaccuracy of Initial Clinical Mobility Assessment in Venous Thromboembolism Risk Stratification

Background: The risk of Venous Thromboembolism (VTE) often escalates in hospital settings in part due to reduced patient mobility. However, mobility assessment for VTE risk determination is often clouded by lack of clear definitions and standards. This vagueness can result in erroneous evaluations, especially near the time of admission, particularly since a patient's mobility is not static but fluctuates throughout the hospital stay. Methods: We conducted a retrospective cohort analysis of patients who were discharged from medicine services in a large academic hospital. For each of these patients, daily nurse-collected Johns Hopkins-Highest Level of Mobility (JH-HLM) scores were used to calculate an objective measure of mobility. Reduced mobility was defined as an JH-HLM score of ≤3 on three consecutive days during hospitalization. We compared this definition of reduced mobility with clinician reported immobility as reflected by Padua scores entered on admission as part of mandatory VTE risk stratification. We also assessed the association between immobility and VTE using an adjusted odds ratio controlling for other VTE risk factors. Results: Out of 1715 included patients, clinicians identified only 111 (6.5%) as having reduced mobility compared with 328 patients (19.1%) using the JH-HLM calculated approach. If the JH-HLM calculated measure of reduced mobility had been utilized, it would have led to the reclassification of 37 patients from a low-risk category to a high-risk category for VTE. In the cohort, 33 of 1715 (1.9%) patients developed VTE. Among these patients, JH-HLM calculated reduced mobility was identified in 12/33 (36%) of patients, whereas clinicians identified reduced mobility in 3/33 (9%) of patients. Presence of JH-HLM calculated reduced mobility was significantly associated with VTE events (aOR: 2.53, 95% CI: 1.23 - 5.22, P = 0.012). Clinician assessed reduced mobility at the time of admission was not associated with VTE events. Conclusion: The initial clinician's assessment of mobility during VTE risk assessment did not accurately capture the extent of reduced mobility during the patient's hospitalization. These findings highlight the importance of employing objective measures of patient mobility for assessing and reassessing VTE risk throughout the hospital stay. Healthcare organizations should consider implementing objective measures of mobility like the JH-HLM to improve VTE risk assessment and potentially reduce the occurrence of VTE.

Development and External Validation of a Lymphoma-Specific Venous Thromboembolism Risk Assessment Model

Introduction: Venous thromboembolism (VTE) significantly affects cancer patients undergoing systemic therapy. Existing risk models developed in the pan-cancer population, such as the Khorana score, offer limited discrimination in cancer-specific setting. We aimed to develop and validate a risk assessment model (RAM) tailored for lymphoma patients, accounting for the clinical and sociodemographic heterogeneity across three distinct healthcare systems in the United States. Methods: Electronic health records (EHR) linked to cancer registry 2006-2021 from the Veterans Affairs national healthcare system (VA) with a total of 10,313 lymphoma patients were randomly divided into an 80% derivation cohort and a 20% internal validation cohort. Further external validation was carried out using data from two other healthcare systems - Harris Health System (HHS, N= 854, 2011-2020) and MD Anderson Cancer Center (MDACC, N=1,858, 2017-2020). Patients were included if they had newly diagnosed lymphoma requiring first-line systemic therapy within 1 year of diagnosis. Patients were excluded if they had recent diagnosis of acute VTE within the last 6 months or were prescribed anticoagulant within 1 month before index date. The index date was the time of systemic therapy, and all covariates were extracted on or before the index date. Incident VTE was defined using our published computable phenotype algorithm (PMID 36626707; 37067102). For RAM derivation (Figure 1), 32 candidate predictors were initially chosen based on clinical relevance and EHR data availability. Missing values were imputed via chain random forest. Parsimonious variable categories were selected by a combination of Least Absolute Shrinkage and Selection Operator (LASSO), Recursive Feature Elimination (RFE), and random forest to generate the final logistic regression model. For external validation, complete case analysis was performed using the derived beta coefficients without model refitting. Bootstrapped time-dependent c statistics and calibration curves for 6-month VTE were used to assess discrimination and fit. A pre-determined threshold of 8% VTE at 6-month from the predicted probability was used to stratify high vs. low-risk groups. Competing risk models were used to assess cumulative incidence. Results: At 6 months, the VTE incidence were 5.75% (n=469) in VA derivation and 6.12% (n=124), 8.24% (n=69), and 6.55% (n=112) in the VA, HHS, and MDACC validation cohorts, respectively. The three healthcare systems had different baseline characteristics in demographics, lymphoma types, systemic therapies, and comorbidities. Patients from VA were mostly older males with more comorbidities and remote history of VTE, patients from HHS were mostly uninsured minorities who were younger but with more aggressive histology, while those from MDACC were patients treated at a comprehensive cancer center. The variables in the final RAM included lymphoma type (4 groups ranging from very-low to very-high risk), body mass index, indwelling catheter, cytotoxic vs. targeted therapy, history of VTE, recent hospitalization, and paralysis/immobilization. Table 1 shows the variable prevalence in each cohort. As shown in Figure 1, the new RAM showed promising discrimination for VTE with a C-statistic of 0.69 in the derivation cohort and 0.67, 0.70, 0.72 in the internal and two external validation cohorts. By splitting patients using an 8% predicted risk threshold, the high- vs. low-risk group achieved a clear differentiation in risk stratification despite significant differences in baseline characteristics. This represented a noticeable improvement for lymphoma patients over the Khorana Score, which yielded C-statistics of 0.53-0.56. The overall calibration of the RAM appeared adequate. Conclusions: Using multiple cancer-EHR cohorts with heterogeneous patients and a wide range of lymphoma subtypes, we successfully derived and externally validated an improved RAM for VTE specifically in lymphoma patients requiring early initiation of systemic therapy. Along several well-known patient-specific risk factors, lymphoma type was an important predictor of VTE risk. The new RAM could improve VTE risk stratification and prevention efforts in lymphoma patients.

DNA Liquid Biopsies for Cancer-Associated Venous Thromboembolism Prediction

Introduction Cancer-associated venous thromboembolism (VTE) is a major source of oncologic cost, morbidity and mortality. Identifying an optimal population for prophylactic anticoagulation is challenging and adds to clinician overhead. Circulating tumor (ct)DNA sequencing assays (“liquid biopsies”) are increasingly deployed in clinic, with multiple US FDA approvals for matching to molecularly targeted therapy. Preliminary data suggest that cell-free (cf)DNA, which is also measured as part of liquid biopsies and may consist of tumor or wild-type DNA, is thrombogenic due to its association with neutrophil extracellular traps. However, clinical validation of cfDNA for VTE prediction is lacking. ctDNA detection is associated with aggressive tumor biology and worse survival; however, whether it is associated with VTE is unknown. To address these gaps, we studied the clinical utility of ctDNA and cfDNA from liquid biopsies for predicting VTE. Methods We conducted an observational study in two cohorts: 1) Patients with any cancer type at Memorial Sloan Kettering Cancer Center (MSK, New York USA), an academic medical center, with plasma ctDNA sequencing using MSK-ACCESS, a NY State-approved, 129-gene assay (N=4,141). 2) A nonoverlapping cohort of patients at MSK or GenesisCare (Sydney, Australia), a community oncology setting, with stage IV or recurrent non-small cell lung cancer and ctDNA sequencing using a separate commercial assay (Agilent ctDx Lung, N=463). We studied the independent contribution of ctDNA, cfDNA and related variables for predicting VTE using Cox proportional hazards. We studied the potential utility of DNA liquid biopsies for predicting VTE within six months using machine learning models, comparing their dynamic area under the receiver operating curve, precision, and recall to those of the Khorana score, the most widely implemented risk metric. We tested the impact of ongoing anticoagulation for non-VTE indications on future VTE in patients with and without detectable ctDNA using nonrandomized, real-world evidence. Results ctDNA detection was associated with an increased risk of VTE in a dose-dependent manner (Figure 1). This association was observed across assays and treatment sites and regardless of genomic subtype. ctDNA was associated with VTE risk in non-small cell lung, breast, pancreatic, prostate, and less represented cancers as well as melanoma but not in bladder, hepatobiliary, or colorectal cancer. By contrast, cfDNA concentration was associated with VTE risk in all cancer types. In multivariate analysis, ctDNA detection, cfDNA concentration, Khorana score, chemotherapy treatment within 30 days, and number of organ sites of metastasis were all independently associated with VTE. In a cohort of patients with treatment naive lung adenocarcinoma with segmented positron emission tomography scans, ctDNA was an independent predictor of VTE after controlling for metabolic tumor volume. A random survival forest machine learning model to predict VTE within six months of plasma draw using liquid biopsy data (i.e. cfDNA and ctDNA levels as well as genomic content), cancer type, and chemotherapy receipt (“LB+”) outperformed the Khorana score in 5-fold cross-validation and was similarly superior in the external lung cohort (Table 1). The superiority of the model was observed in patients treated or not treated with chemotherapy. Additional clinical and radiologic data, including demographics, metastatic sites of disease, and Khorana score components (“All”), did not improve the ctDNA assay-based LB+ model. Patients with anticoagulation had lower VTE rates if ctDNA was detectable (adjusted HR 0.54, 95%CI 0.33-0.87) but not if ctDNA was undetectable. Conclusion In patients with cancer, ctDNA and cfDNA are independent biomarkers for VTE. Risk models incorporating liquid biopsy data are feasible in academic or community settings and, if prospectively validated, would provide a means of VTE risk stratification at scale.

Impact of integrating standardized venous thromboembolism (VTE) prophylaxis orders for patients with multiple myeloma into an electronic health record (EHR).

469 Background: VTE is a serious complication in multiple myeloma patients, who have a 9-fold increased risk compared to the general population. Prophylaxis for VTE is recommended by international guidelines in multiple myeloma patients based on VTE risk assessment, but published studies have demonstrated prescribing may be suboptimal. Our aim was to evaluate the impact of integrating standardized VTE prophylaxis orders for multiple myeloma patients on active treatment into our EHR, which services over 2300 providers within 500 community cancer treatment locations across the United States. Methods: National Comprehensive Cancer Network Guideline-recommended VTE prophylaxis agents were integrated as optional orders into multiple myeloma EHR regimen templates from June to July 2022. Optional informational orders were also included: a “VTE Prophylaxis Reminder” order served as a trigger for the care team if prophylaxis was not prescribed and a “VTE Prophylaxis Exception” order served as documentation if the patient did not qualify for anticoagulation. An educational guide about VTE risk stratification and prophylaxis in multiple myeloma was developed and embedded in regimen templates. To evaluate the impact of this intervention, a structured EHR data export was used to identify multiple myeloma patients with regimen templates ordered during the prespecified time frames. A retrospective chart review was conducted to identify documentation of anticoagulation or reason for exception on or prior to cycle 1 day 1 of the multiple myeloma regimen. Data were compared using the Fisher’s exact test. We also evaluated ordering of VTE prophylaxis and use of informational orders from regimens during the post-implementation phase. Results: A total of 297 patients were identified, with 128 during the pre-implementation phase (May 2022) and 169 during the post-implementation phase (September 2022). Documentation of anticoagulation or reason for exception on or prior to cycle 1 day 1 of the multiple myeloma regimen increased from 70% (89/128) during the pre-implementation phase to 81% (137/169) during the post-implementation phase (two-sided p=0.0276). Aspirin was the most common agent prescribed in 73% and 64% of patients, respectively. During the post-implementation phase, VTE prophylaxis was prescribed directly from the regimen in 16% of patients. The “VTE Prophylaxis Reminder” order was utilized for 89% of patients and the “VTE Prophylaxis Exception” order was utilized for 1 patient. Conclusions: Integration of standardized orders into EHR regimen templates may facilitate prescribing and serve as reminders for the care team. We saw an 11% increase in documentation of VTE prophylaxis, which may potentially reduce risk of VTE in this patient population. Efforts are ongoing to highlight the need for anticoagulation and importance of documentation.

Risk stratified venous thromboembolism prophylaxis in bariatric patients using a Caprini assessment: practice patterns and opportunities for improvement

BackgroundVenous thromboembolism (VTE) is rare after bariatric surgery but is the most common cause of mortality. The use of VTE risk-stratification tools and compliance with practice guidelines remain unclear. ObjectivesOur objectives were to determine the utilization of risk-stratified VTE prophylaxis and its impact on VTE and bleeding outcomes. SettingAcademic hospital system. MethodsRoux-en-Y gastric bypass and sleeve gastrectomy (2016–2021) were identified from our electronic health records. Caprini score and VTE prophylaxis regimen were retrospectively determined. VTE prophylaxis consistent with Caprini guidelines was considered appropriate. Outcomes were compared between VTE prophylaxis cohorts. Variables were compared by Kruskal–Wallis test, Pearson χ2 test, and regression models. A P value of <.05 was considered significant. ResultsA total of 1849 bariatric cases were analyzed, including 64% Roux-en-Y gastric bypass and 36% sleeve gastrectomy cases. Of these, 70% and 3.7% received appropriate risk-stratified VTE prophylaxis during hospitalization and at discharge. The mean Caprini score was higher in those without appropriate prophylaxis (8.45 versus 8.04; P = .0004). Inpatient and 30- and 90-day VTE rates were .22%, .47%, and .64%. All discharge VTE events occurred in those not receiving appropriate Caprini risk-stratified VTE prophylaxis. Inpatient and 30- and 90-day bleeding complications were .22%, .23%, and .35%. The likelihood of receiving appropriate prophylaxis varied by hospital site, and receiving appropriate prophylaxis was not associated with increased bleeding risk. ConclusionCaprini guideline–indicated VTE prophylaxis can be safely used in bariatric surgery patients and may reduce preventable VTE complications without increasing bleeding risk.

Incidence, risk factors, and outcomes of venous thromboembolism in patients undergoing surgery for retroperitoneal tumors: A propensity-matched retrospective cohort study.

Venous thromboembolism (VTE) is a common postoperative complication; however, incidence and risk stratification of postoperative VTE in patients with retroperitoneal tumor remains unclear. We aim to quantify incidence, identify risk factors, and determine outcomes of VTE in patients undergoing retroperitoneal tumor surgery. We retrospectively reviewed characteristics, perioperative outcomes, and overall survival (OS) of patients (VTE and non-VTE) who underwent retroperitoneal tumor surgery between 2015 and 2020. Perioperative and oncologic outcomes were compared using propensity-matching and Cox analyses. Of 1223 patients with retroperitoneal tumor surgery, 2.1% had VTE. Age (odds ratio [OR] 1.140, 95% confidence interval [CI] 1.053-1.239, P=0.004), recurrence (OR 1.851, 95% CI 1.241-2.761, P=0.003), and vascular resection (OR 2.036, 95% CI 1.054-3.934, P=0.034) were independent risk factors, with significant between-group differences regarding age, recurrence, sarcoma, organ resection, vascular resection, and operation time. No between-group differences in 30-day all-cause mortality (8% vs. 4%, OR 0.657, 95% CI 0.375-1.151, P=0.427) and major complications (12% vs. 8%, OR 0.775, 95% CI 0.483-1.244, P=0.572) were observed. Mean hospitalization duration (20.1 vs. 22.9d, OR 1.153, 95% CI 1.022-1.386, P=0.033) and ICU stay (3.2 vs. 5.5d, OR 1.193, 95% CI 1.034-1.347, P=0.012) were shorter in non-VTE versus VTE, respectively, with inferior OS (hazard ratio [HR] 2.090, 95% CI 1.014-4.308, P=0.046) in VTE. Age, recurrence, and vascular resection are positively associated with VTE, which is associated with inferior OS.

Venous thromboembolism (VTE) prophylaxis after bariatric surgery: a national survey of MBSAQIP director practices.

Venous thromboembolism (VTE) is the most common cause of death following metabolic/bariatric surgery (MBS), with most events occurring after discharge. The available evidence on ideal prophylaxis type, dosage, and duration after discharge is limited. Assess metabolic/bariatric surgeon VTE prophylaxis practices and define existing variability. Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP)-accredited centers. The members of the ASMBS Research Committee developed and administeredaweb-based survey to MBSAQIP medical directors and ASMBS members to examine the differences in clinical practice regarding the administration of VTE prophylaxis after MBS. Overall, 264 metabolic/bariatric surgeons (136 medical directors and 128 ASMBS members) participated in the survey. Both mechanical and chemical VTE prophylaxis was used by 97.1% of the participants, knee-high compression devices by 84.7%, enoxaparin (32.4% 40 mg every 24 hours, 22.7% 40 mg every 12 hours, 24.4% adjusted the dose based on body mass index) by 56.5%, and heparin (46.1% 5000 units every 8 hours, 22.6% 5000 units every 12 hours, 20.9% 5000 units once preoperatively) by 38.1%. Most surgeons (81.6%) administered the first dose preoperatively, while the first postoperative dose was given on the evening of surgery by 44% or the next morning by 42.2%. Extended VTE prophylaxis was prescribed for 2 weeks by 38.7% and 4 weeks by 28.9%. VTE prophylaxis practices vary widely among metabolic/bariatric surgeons. Variability may be related to limited available comparative evidence. Large prospective clinical trials are needed to define optimal practices for VTE risk stratification and prophylaxis in bariatric surgery patients.

Are Patients With Morbid Obesity at Increased Risk of Pulmonary Embolism or Proximal Deep Vein Thrombosis After Lower Limb Arthroplasty? A Large-database Study.

Whether increased BMI is associated with an increased risk of venous thromboembolism (VTE) is controversial. Despite this, BMI > 40 kg/m 2 remains a common cutoff for lower limb arthroplasty eligibility. Current United Kingdom national guidelines list obesity as a risk factor for VTE, but these are based on evidence that has largely failed to differentiate between potentially minor (distal deep vein thrombosis [DVT]), and more harmful (pulmonary embolism [PE] and proximal DVT) diagnoses. Determining the association between BMI and the risk of clinically important VTE is needed to improve the utility of national risk stratification tools. (1) In patients undergoing lower limb arthroplasty, is BMI 40 kg/m 2 or higher (morbid obesity) associated with an increased risk of PE or proximal DVT within 90 days of surgery, compared with patients with BMI less than 40 kg/m 2 ? (2) What proportion of investigations ordered for PE and proximal DVT were positive in patients with morbid obesity who underwent lower limb arthroplasty compared with those with BMI less than 40 kg/m 2 ? Data were collected retrospectively from the Northern Ireland Electronic Care Record, a national database recording patient demographics, diagnoses, encounters, and clinical correspondence. Between January 2016 and December 2020, 10,217 primary joint arthroplasties were performed. Of those, 21% (2184 joints) were excluded; 2183 were in patients with multiple arthroplasties and one had no recorded BMI. All 8033 remaining joints were eligible for inclusion, 52% of which (4184) were THAs, 44% (3494) were TKAs, and 4% (355) were unicompartmental knee arthroplasties; all patients had 90 days of follow-up. The Wells score was used to guide the investigations. Indications for CT pulmonary angiography for suspected PE included pleuritic chest pain, reduced oxygen saturations, dyspnea, or hemoptysis. Indications for ultrasound scans for suspected proximal DVT included leg swelling, pain, warmth, or erythema. Distal DVTs were recorded as negative scans because we do not treat them with modified anticoagulation. The division of categories was set at BMI 40 kg/m 2 , a common clinical cutoff used in surgical eligibility algorithms. Patients were grouped according to WHO BMI categories to assess for the following confounding variables: sex, age, American Society of Anesthesiologists grade, joint replaced, VTE prophylaxis, grade of operative surgeon, and implant cement status. We found no increase in the odds of PE or proximal DVT in any WHO BMI category. When comparing patients with BMI less than 40 kg/m 2 with those with a BMI of 40 kg/m 2 or higher, there was no difference in the odds of PE (0.8% [58 of 7506] versus 0.8% [four of 527]; OR 1.0 [95% CI 0.4 to 2.8]; p > 0.99) or proximal DVT (0.4% [33 of 7506] versus 0.2% [one of 527]; OR 2.3 [95% CI 0.3 to 17.0]; p = 0.72). Of those who received diagnostic imaging, 21% (59 of 276) of CT pulmonary angiograms and 4% (34 of 718) of ultrasounds were positive for patients with BMI less than 40 kg/m 2 compared with 14% (four of 29; OR 1.6 [95% CI 0.6 to 4.5]; p = 0.47) and 2% (one of 57; OR 2.7 [95% CI 0.4 to 18.6]; p = 0.51) for patients with BMI 40 kg/m 2 or higher. There was no difference in the percentage of CT pulmonary angiograms ordered (4% [276 of 7506] versus 5% [29 of 527]; OR 0.7 [95% CI 0.5 to 1.0]; p = 0.07) or ultrasounds ordered (10% [718 of 7506] versus 11% [57 of 527]; OR 0.9 [95% CI 0.7 to 1.2]; p = 0.49) for BMI less than 40 kg/m 2 and BMI 40 kg/m 2 or higher. Increased BMI should not preclude individuals from lower limb arthroplasty based on suspected risk of clinically important VTE. National VTE risk stratification tools should be based on evidence assessing clinically relevant VTE (specifically, proximal DVT, PE, or death of thromboembolism) only. Level III, therapeutic study.

Prognostic value of D-dimers in patients with COVID-19: narrative synthesis

Introduction. Contemporary researchers have suggested and demonstrated the hypothesis that the elevated level of D-dimers, which is a valuable marker of coagulation and fibrinolysis activation, can predict the severity of COVID-19, pulmonary complications, and thromboembolic events before they occur.&#x0D; Material and methods. The bibliographic resources were analyzed and selected from databases such as PubMed, Hinari, SpringerLink, and Google Search using keywords such as “COVID-19,” “SARS-CoV-2,” “coronavirus,” “D-dimers,” “biomarkers,” and “severity prediction,” which were used in various combinations to maximize search efficiency. Therefore, the manuscript contains 51 representative articles for the purpose of this synthesis article.&#x0D; Results. The D-dimer levels are significantly higher in patients with severe forms of COVID-19 compared to those with non-severe forms, in patients with acute respiratory distress syndrome compared to those without acute respiratory distress syndrome, and in deceased patients compared to those who have survived. D-dimers positively correlate with the degree of severity and the increased risk of progression to severe disease, inversely proportional to the survival rate. They can predict prognosis, determine therapeutic strategies, prevent complications, positively influence the disease’s course, and monitor the prognosis.&#x0D; Conclusions. D-dimers should be used as a pre-radiographic screening tool as early as possible after admission and as an indicator for risk stratification of venous thromboembolism in hospitalized patients with COVID-19. Based on the increase in D-dimer levels, adjusting therapeutic doses of anticoagulants is more beneficial for patients compared to administering prophylactic doses.

Stratification of Venous Thromboembolism Risk in Multiple Myeloma and Analysis of the Use of Antithrombotic Agents

Stratification of Venous Thromboembolism Risk in Multiple Myeloma and Analysis of the Use of Antithrombotic Agents