Venous Thromboembolism Risk Assessment Model Research Articles

Venous Thromboembolism Risk Assessment Models for Acutely Ill Medical Patients—Back to the Drawing Board?

Venous Thromboembolism Risk Assessment Models for Acutely Ill Medical Patients—Back to the Drawing Board?

Sustained Success of a Caprini Postoperative Venous Thromboembolism Prevention Protocol Over One Decade

BackgroundThe objective of this study was to review the long-term efficacy of a post-operative venous thromboembolism (VTE) prevention program at our institution. MethodsWe performed a review of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data at our hospital during January 2008-December 2022. The primary outcome was risk-adjusted VTE events. ResultsIn 2009, a postoperative general surgery patient was three times more likely to have a postoperative VTE event than predicted (O/E ratio 3.02, 95% CI 1.99-4.40). After implementing a mandatory VTE risk assessment model and a risk-commensurate prophylaxis protocol in the electronic medical record in 2011, the odds ratio of a patient developing a postoperative VTE declined to 0.70 by 2014 (95% CI 0.40-1.23). This success persisted through 2022. ConclusionsSince the implementation of a standardized postoperative VTE prevention program in 2011, our institution has sustained a desirably low likelihood of VTE events in general surgery patients.

Converting IMPROVE bleeding and VTE risk assessment models into a fast-and-frugal decision tree for optimal hospital VTE prophylaxis

AbstractCurrent hospital venous thromboembolism (VTE) prophylaxis for medical patients is characterized by both underuse and overuse. The American Society of Hematology (ASH) has endorsed the use of risk assessment models (RAM) as an approach to individualize VTE prophylaxis by balancing overuse (excessive risk of bleeding) and underuse (risk of avoidable VTE). ASH has endorsed IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) risk assessment models: the only RAM to assess short-term bleeding and VTE risk in acutely ill medical inpatients. ASH, however, notes that no RAMs have been thoroughly analyzed for their effect on patient outcomes. We aimed to validate the IMPROVE models and adapt them into a simple, fast-and-frugal (FFT) decision tree to evaluate the impact of VTE prevention on health outcomes and costs. We used 3 methods: the “best evidence” from ASH guidelines, a “learning health system paradigm” combining guideline and real-world data from the Medical University of South Carolina (MUSC), and a “real-world data” approach based solely on MUSC data retrospectively extracted from electronic records. We found that the most effective VTE prevention strategy used the FFT decision tree based on an IMPROVE VTE score of ≥2 or ≥4 and a bleeding score of <7. This method could prevent 45% of unnecessary treatments, saving ∼$5 million annually for patients such as the MUSC cohort. We recommend integrating IMPROVE models into hospital electronic medical records as a point-of-care tool, thereby enhancing VTE prevention in hospitalized medical patients.

An Effective Protocol for Perioperative Venous Thromboembolism Prophylaxis in DIEP Flap Breast Reconstruction: A Single Institution Retrospective Review.

Deep inferior epigastric artery perforator (DIEP) free flap breast reconstruction is one of the most highly used procedures for autologous breast reconstruction. Many venous thromboembolism (VTE) risk assessment models have been proposed in breast reconstructive surgery, including the widely used Caprini score. However, a paucity of data suggests an effective standardized VTE protocol. The purpose of this study was to determine the rate of VTE in our DIEP flap patients who were treated with this protocol. A retrospective single-center review of DIEP flap breast reconstruction from 2016 to 2021 was performed. Data were collected on 554 patients and 893 flaps including demographics, intraoperative and perioperative details, and postoperative course. Patients who were not treated with our standard protocol were excluded. Data were analyzed with alpha = 0.05. The average age was 50.4 ± 9.9 years, and the total follow-up time was 16.9 ± 12.6 months. The average body mass index for the cohort was 30.1 ± 5.2. During the 90 postoperative days, the mean length of hospital stay was 4.3 days. There were six cases of postoperative VTE: five patients presented with pulmonary embolism (0.9%) and one patient (0.2%) had deep venous thrombosis with an overall VTE prevalence of 1.1%. No specific single factor could be attributed to VTE occurrence. Using our standardized VTE prophylaxis protocol, our institution was effective at keeping VTE rates low. Additional studies would be beneficial to determine optimal VTE prophylaxis protocols in higher-risk patients, such as those with known clotting disorders.

The Use of Risk Scores for Thromboprophylaxis in Medically Ill Patients-Rationale and Design of the RICO trial.

Background Venous thromboembolism (VTE) in hospitalized medically ill patients is a significant cause of morbidity and mortality. Guidelines suggest that VTE and bleeding risk assessment models (RAMs) should be integrated into the clinical decision-making process on thromboprophylaxis. However, poor evidence is available comparing the use of a RAM versus clinical judgement in evaluating VTE and bleeding occurrence. Methods Reducing Important Clinical Outcomes in hospitalized medical ill patients (RICO) is a multicenter, cluster-randomized, controlled clinical trial (ClinicalTrials.gov Identifier: NCT04267718). Acutely ill patients hospitalized in Internal Medicine wards are randomized to the use of RAMs-namely the Padua Prediction Score and the International Medical Prevention Registry on Venous Thromboembolism Bleeding Score-or to clinical judgement. The primary study outcome is a composite of symptomatic objectively confirmed VTE and major bleeding at 90-day follow-up. Secondary endpoints include the evaluation of clinical outcomes at hospital discharge and the assessment of VTE prophylaxis prescription during the study period. In order to demonstrate a 50% reduction in the primary outcome in the experimental group and assuming an incidence of the primary outcome of 3.5% in the control group at 90-day; 2,844 patients across 32 centers will be included in the study. Discussion The RICO trial is a randomized study of clinical management assessing the role of RAMs in hospitalized medical ill patients with the aim of reducing VTE and bleeding occurrence. The study has the potential to improve clinical practice since VTE still represents an important cause of morbidity and mortality in this setting.

Evaluation of Clinical Risk Factors and Thrombosis-Related Biomarkers in Newly Diagnosed Patients with Multiple Myeloma at Risk for Cancer-Associated Thrombosis. the Observational Roadmat-CAT-MM Study

Background: Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. Multiple myeloma (MM) figures among malignancies that significantly increase the risk of venous thromboembolism (VTE). The rate of VTE is higher at the time of diagnosis and during the first months following initiation of first line therapy; approximately 10% of newly diagnosed MM (NDMM) will develop a VTE. Despite adequate thromboprophylaxis as per guidelines, the risk of residual VTE is not eliminated and remains as high as 12%. The optimization of VTE prevention in patients with MM is an unmet need. The exact mechanism of the increased risk of VTE is not yet fully understood. The identification of the procoagulant potential of cancer cells, which is related principally to tissue factor (TF) expression, attracts particular interest. Aim: We conducted a longitudinal prospective observational study, to explore the relationship of MM with cellular and plasma hypercoagulability as well as tissue factor positive microparticles, aiming to identify the most relevant biomarkers, which could be used in a Risk Assessment Model (RAM) for VTE in combination with clinical risk factors. Methods: Newly diagnosed patients (182) with multiple myeloma (NDMM) were prospectively enrolled. Patients were followed up for 12 months and the primary end-point was symptomatic objectively confirmed VTE. Patients were risk stratified and received thromboprophylaxis (none, aspirin on low molecular weight heparin (LMWH) based on previously published recommendations by the IMWG and EMN. Prior to treatment initiation and thromboprophylaxis initiation baseline biomarkers were obtained: Thrombin generation (TGT) in citrated PPP was assessed with the Thrombogram-Thrombinoscope® assay using PPP-reagent® 5 pm TF by Diagnostica Stago. The levels of P-Selectin and heparanase in plasma were measured with ELISA Kit (Cusabio Biotech and R&amp;D Systems respectively). The procoagulant phospholipids clotting time was measured with STA-Procoag-PPL®, Levels of Factor VIIa were measured by Staclot VIIa-rTF®, D-Dimers (DDi) by Liatest D-Di (Diagnostica Stago, France), and Tissue Factor activity (TFa) by specific clotting based home test. TF expression MPC-derived microparticles (MPC-dMPs) were detected using a Zymuphen MP-TF activity kit (Hyphen BioMed, Neuville sur Oise, France). These were compared against values in a population of healthy individuals (n=30). Results: The distribution of patients enrolled in the study is as follows: Median age was 67 years (36-86) and 52% of the population was male. Median time to follow up was 7 months (1-12 months). The control group (30 healthy individuals). The overall rate of symptomatic VTE during follow-up was 11.5% (n = 21 patients). Eleven out of 21 events (52%) occurred within 3 months from treatment initiation. Six of these patients did not receive any thromboprophylaxis; six patients were on aspirin at the time of the event and three were on LMWH.At inclusion, patients showed significantly increased levels of TFa, FVIIa, D-Dimers and FM, and significantly shorter Procoag-PPL® as compared to the group of healthy individuals. Levels of P-selectin and TM were significantly lower in patients as compared to healthy individuals. The levels of heparanase were not significantly different in the group of patients as compared to the healthy individuals. Overall thrombin generation was attenuated in patients compared to healthy individuals. Lag-time and ttPeak were significantly increased and Peak, MRI, and ETP were significantly lower as compared to the control group, MP-TF activity measured in NDMM significantly increased 1.46± 0.38 pg/mL compared to control subjects 0.19 ± 0.05 pg/mL (Table 1). Multivariate logistic regression analysis demonstrated that ETP, Procoag-PPL® and MP-TF were independently associated with VTE occurrence. (Table 2) Conclusion: The prospective ROADMAP-CAT-MM study demonstrates the presence of pronounced cellular hypercoagulability in newly diagnosed chemotherapy naïve patients with MM characterized by decreased Procoag-PPL® clotting time, enhanced endothelial cell activation, and exhausted thrombin generation. The Procoag-PPL clotting time and the ETP and MP-TF were found to be independently associated with the risk of VTE and can be prospectively incorporated into a RAM for VTE in MM.

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.

Underestimation of Venous Thromboembolism Risk: A Common Health Care Quality Deficit

Venous thromboembolism (VTE) is a complication of hospitalization but not all patients are at high risk. VTE risk assessment models have been developed to identify patients whose risk is sufficient to warrant pharmacologic thromboprophylaxis. To ensure all patients are risk assessed upon admission, we implemented a mandatory risk assessment tool embedded in admission order sets in our electronic health record (EHR) system. We hypothesized that the accuracy of these risk assessments was variable. We performed a retrospective cohort study of patients discharged from the Johns Hopkins Hospital medicine service between January 1 st-December 31 st 2019. The cohort consisted of consecutive patients classified into normal, intermediate or low mobility groups using the Johns Hopkins Highest Level of Mobility score. Using a standardized chart review algorithm, elements of the Padua and Improve risk scores were determined using the admission note and the JH-HLM scores for mobility assessment. We report the results of the Padua score comparison. Provider risk assessments, VTE prophylaxis orders, symptomatic VTE, major bleeding (ISTH criteria) and deaths were determined by chart review. We measured concordance between provider risk factors identified and those identified on retrospective chart review. Statistical analyses were done using Chi-squared or Fisher's exact test and were performed using Stata v.18. The cohort consist of 2992 patients with a median age of 58 (Interquartile range (IQR) 45-70). Characteristics of the cohort are in Table 1. The median provider Padua score was 1 (IQR 0,3) compared with 2 (IQR 1,5) for chart review. Providers identified 2480 patients (82.9%) as being low risk compared with 1882 (62.9%) upon chart review (P&amp;lt;0.001). Differences in risk factor assessments are presented in Figure 1. Concordance rates between providers and chart review were high (93.6%-99.6%) for all risk factors except obesity (87.5%), heart failure (76.4%), reduced mobility (72.5%) and acute infection (66.1%).(Figure 1) Thirty-six VTE (27 DVT, 9 PE; 1.2%) occurred during the hospital stay and sixty-one (44 DVT;17 PE; 2.2%) within 3 months. Among patients who suffered an in-hospital VTE, providers assessed 29 (80.6%) as low risk compared with 13 (36.1%) by chart review. Fourteen patients (48.3%) were not prescribed prophylaxis. Forty-seven of 61 patients (77.0%) who developed VTE within 3 months were classified as low risk by providers compared with 26 (42.6%) among chart reviewers. Twenty-five (41.0%) were not prescribed prophylaxis. 727 of 2480 (29.3%) patients risk assessed as low risk by providers were assessed as being at high risk upon chart review. 707 of 2480 (28.5%) low risk patients were not prescribed prophylaxis. 157 of these 707 (22.2%) would have been prescribed prophylaxis based upon chart review. Among these 157 patients, 7 VTE occurred during the hospital stay and 11 events occurred within 3 months. Major bleeding occurred during prophylaxis in 4 patients (0.17%). Underestimation of VTE risk is common in hospitalized medically-ill patients. Development of improved EHR VTE risk assessment tools that assist the provider in identifying patient risk factors could improve VTE prevention and reduce hospital-associated VTE.

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.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma

BackgroundIndividuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.MethodsWe retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.ResultsThe overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.ConclusionsThe new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Generalizability of COBRA: A Parsimonious Perioperative Venous Thromboembolism Risk Assessment Model

IntroductionStandardized use of venous thromboembolism (VTE) risk assessment models (RAMs) in surgical patients has been limited, in part due to the cumbersome workflow addition required to use available models. The COBRA score—capturing cancer diagnosis, (old) age, body mass index, race, and American Society of Anesthesiologists Physical Status score—has been reported as a potentially automatable VTE RAM that circumvents the cumbersome workflow addition that most RAMs represent. We aimed to test the ability of the COBRA model to effectively risk-stratify patients across various populations. MethodsPatients were included from the 2014-2019 American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Participant Use Data File for two hospitals, representing colorectal, endocrine, breast, transplant, plastic, and general surgery services. COBRA score was calculated for each patient using preoperative characteristics. We calculated negative predictive value (NPV) for VTE outcomes and compared the COBRA score to NSQIP's expected VTE rate for all patients, between the two hospitals, and between subspecialty service lines. ResultsOf the 10,711 patients included, those with COBRA <4 (31%) had projected median VTE rate of 0.21% (interquartile range, 0.09-0.68%; mean, 0.54%). Patients with higher scores (69%) had median rate of 0.88% (0.26-2.07%; 1.46%); relative rate 2.7. The median projected VTE rates for patients identified as low risk were 0.21% and 0.16% and as high risk were 0.87% and 0.89% at hospitals one and 2, respectively. The median projected VTE rates for patients identified as low risk were 0.17%, 0.61%, and 0.08% and as high risk were 0.52%, 1.43%, and 0.18% among general, colorectal, and endocrine surgery patients, respectively. COBRA had NPV of 0.995 and sensitivity of 0.871 as compared to NPV 0.997 and sensitivity 0.857 of the NSQIP model. ConclusionsThe COBRA score is concordant with the traditional gold standard NSQIP VTE RAM and demonstrates interhospital and service-specific generalizability, although performance was limited in especially low-risk patients. The model adequately risk-stratifies surgical patients preoperatively, potentially providing clinical decision support for perioperative workflows.

Simple yet (more?) effective. Venous thromboembolism risk assessment model for germ cell tumour patients receiving first-line chemotherapy.

Germ cell tumours (GCT) are highly curable malignancies. Venous thromboembolism (VTE) is a serious complication, needing better risk assessment models (RAM). Identification of VTE incidence and risk factors in metastatic GCT patients starting first-line chemotherapy. Developing a RAM and comparing it to Khorana risk score (KRS) and Padua Prediction Score (PPS). We retrospectively analysed GCT patients staged IS-IIIC. VTE risk factors were identified with logistic regression. Area under curve of receiver operating characteristic (AUC-ROC), Akaike and Bayesian Information Criteria (AIC, BIC) were calculated for the developed RAM, KRS and PPS. Among 495 eligible patients, VTE occurred in 69 (13.9%), including 40 prior to chemotherapy. Vein compression (OR: 8.96; 95% CI: 2.85-28.13; p < 0.001), clinical stage IIIB-IIIC (OR: 5.68; 95% CI: 1.82-17.70; p = 0.003) and haemoglobin concentration (OR for 1 g/dL decrease: 1.32; 95% CI: 1.03-1.67; p = 0.026) were significant in our RAM. KRS ≥ 3 (OR: 3.31; 95% CI: 1.77-6.20; p < 0.001), PPS 4-5 (OR: 3.06; 95% CI: 1.49-6.29; p = 0.002) and PPS > 5 (OR 8.05; 95% CI 3.79-17.13; p < 0.001) correlated with VTE risk. Diagnostic criteria (AUC-ROC, AIC, BIC) for the developed RAM, KRS and PPS were (0.885; 0.567; -1641), (0.588; 0.839; -1576) and (0.700; 0.799; -1585), respectively. In the numerical score, the optimal cut-off point for high-risk was ≥9, with sensitivity, specificity, positive and negative predictive value of 0.78, 0.77, 0.35 and 0.96, respectively. Our RAM, based on vein compression, clinical stage and haemoglobin concentration proved superior to both KRS and PPS. VTE is frequent in GCT patients.

Venous thromboembolism and bleeding after hepatectomy: role and impact of risk adjusted prophylaxis.

Venous thromboembolism (VTE) occurs in 2-6% of post-hepatectomy patients and is associated with increased mortality and morbidity. The use of VTE risk assessment models in hepatectomy cases remains unclear. Our study aimed to determine the use and impact of Caprini guideline indicated VTE prophylaxis following hepatectomy. Hepatectomy cases performed during 2016-2021 were included. Caprini score andVTE prophylaxis were determined retroactively, and VTE prophylaxis was categorized as appropriate or inappropriate.The primary outcome was the receipt of appropriate prophylaxis, and secondary outcomes were postoperative VTE and bleeding. Statistical analyses included Fisher Exact test, Kruskal-Wallis, Pearson Chi-Square test, and multivariate regression models. R Statistical software was used for analysis. A p-value < 0.05 or 95% Confidence Interval (CI) excluding 1 was considered significant. A total of 1955 hepatectomy cases wereanalyzed. Patient demographics were similar between study cohorts. Inpatient, 30- and 90-day VTE rates were 1.28%, 0.56%, and 1.24%, respectively. By Caprini guidelines, 59% and 4.3% received appropriate in-hospital and discharged VTE prophylaxis, respectively. Inpatient VTE (4.5-fold) and mortality (9.5-fold) were lower in patients receiving appropriate prophylaxis. All discharged VTE and mortality occurred in patients not receiving appropriate prophylaxis. Inpatient, 30- and 90-day bleeding rates were 8.4%, 0.62%, and 0.68%, respectively. Appropriate prophylaxis did not increase postoperative bleeding. Increasing Caprini score inversely correlated with receiving appropriate prophylaxis (OR 0.38, CI 0.31-0.46) at discharge, and appropriate prophylaxis did not correlate with bleeding risk (OR 0.79, CI 0.57-1.12). Caprini guideline indicated prophylaxis resulted in reduced VTE complications without increasing bleeding risk.

Comparison of three risk assessment models for thromboembolism in multiple myeloma patients receiving immunomodulators: a Brazilian historical cohort.

Venous thromboembolism (VTE) is among the complications of Multiple Myeloma (MM) and may occur in up to 10% of this patient population. However, medications used in MM therapy such as immunomodulators (IMID) may raise these rates. Thus, risk prediction models have been developed to quantify the risk of VTE in MM patients. The aim of this study is to compare the performance of three risk assessment models for VTE in newly diagnosed MM (NDMM) patients using immunomodulatory agents. A historical cohort study during a 10-year period in a Brazilian metropolis with NDMM treated with IMID. Data were collected from patient's medical charts for the period of one year to calculate the scores using IMPEDE VTE, SAVED, and International Myeloma Working Group (IMWG) guidelines. The area under the curve (AUC) of the Receiver Operating Characteristic curve analysis was calculated to assess the discriminative power of three risk assessment models. We included 131 patients (9 in the VTE group versus 122 in the non VTE group). According to IMPEDE, 19.1, 62.6, and 18.3% of patients were considered low, intermediate, and high risk, respectively. SAVED classified 32.1% as high risk and 64.9% had ≥2 risk factors based on IMWG guidelines. The AUC of the IMPEDE VTE score was 0.80 (95% CI 0.66-0.95, p = 0.002), of the SAVED score was 0.69 (95% CI 0.49-0.89, p = 0.057), and of the IMWG risk score was 0.68 (95% CI 0.48-0.88, p = 0.075). IMPEDE VTE was the most accurate in predicting the development of VTE in Brazilian patients on IMID therapy. The SAVED score and the IMWG guidelines did not show discriminative ability in predicting VTE based on the population involved in this study.

External Validation of the Padua and IMPROVE-VTE Risk Assessment Models for Predicting Venous Thromboembolism in Hospitalized Adult Medical Patients: A Retrospective Single-Center Study in Japan

Objectives: To assess the external validity of the Padua and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE) risk assessment models (RAMs) for predicting venous thromboembolism (VTE) within 90 days of admission among hospitalized medical patients in Japan. Materials and Methods: A university hospital cohort comprising 3876 consecutive patients ages ≥15 years admitted to a general internal medicine department between July 2016 and July 2021 was retrospectively analyzed using data extracted from their medical records. Results: A total of 74 VTE events (1.9%), including six cases with pulmonary embolism (0.2%), were observed. Both RAMs had poor discriminative performance (C-index=0.64 for both) and generally underestimated VTE risks. However, recalibrating the IMPROVE-VTE RAM to update the baseline hazard improved the calibration (calibration slope=1.01). Decision curve analysis showed that a management strategy with no prediction model outperformed a clinical management strategy guided by the originally proposed RAMs. Conclusions: Both RAMs require an update to function in this particular setting. Further studies with a larger-sized cohort, including re-estimation of the individual regression coefficients with additional, more context-specific predictors, are needed to create a useful model that would help advance risk-oriented VTE prevention programs.

Venous Thromboembolism Risk Assessment in Hospitalized Cancer Patients: A Single Center Study.

This study aimed to identify predictors of venous thromboembolism (VTE) in hospitalized cancer patients and develop a predictive model using demographic, clinical, and laboratory data. Our analysis showed that patient groups categorized under a very high risk, and high risk, patients with low hemoglobin levels and renal disease were at a significantly increased risk of developing VTE. We developed a VTE risk-assessment model (RAM) with moderate discriminatory performance, high specificity, and negative predictive value, indicating its potential utility in identifying patients without VTE risk. However, the model's positive predictive value and sensitivity were low due to the low prevalence of VTE within the analyzed population. Future studies are needed to analyze additional predictive factors, and to validate the effectiveness of our VTE RAM to safely rule out VTE, compare it with other VTE RAMs in hospitalized cancer patients, and address any limitations of our study.

Incidence and Risk Factors for Superficial and Deep Vein Thrombosis in Post-Craniotomy/Craniectomy Neurosurgical Patients.

Background Venous thromboembolism (VTE) is quite common among post-operative neurosurgical patients. This study aims to identify the incidence of deep vein thrombosis (DVT) and superficial vein thrombosis (SVT) among post-craniotomy/craniectomy patients and further evaluate established hypercoagulability risk factors such as trauma, tumors, and surgery. Methodology This single-center retrospective study investigated 197 patients who underwent a craniotomy/craniectomy. The incidences of DVT and SVT were compared, along with laterality and peripherally inserted central catheter (PICC) line involvement. A multivariate logistic regression analysis was conducted to identify risk factors for post-craniotomy/craniectomy VTE. This model included variables such as age, post-operative days before anticoagulant administration, female sex, indications for surgery such as tumor and trauma, presence of a PICC line, and anticoagulant administration. Results Among the 197 post-craniotomy/craniectomy patients (39.6% female; mean age 53.8±15.7 years), the incidences of DVT, SVT, and VTE were 4.6%, 9.6%, and 12.2%, respectively. The multivariate logistic regression analysis found that increasing the number of days between surgery and administration of anticoagulants significantly increased the risk of VTE incidence (odds ratio 1.183, 95% CI 1.068-1.311, p = 0.001). Conclusions Contrary to existing evidence, this study did not find trauma or the presence of tumors to be risk factors for VTE. Future prospective studies should assess VTE risk assessment models such as "3 Bucket" or "Caprini" to develop universal guidelines for administering anticoagulant therapy to post-craniotomy/craniectomy patients that consider the timing of post-operative therapy initiation.

Venous Thromboembolism Risk Assessment Models in Plastic Surgery: A Systematic Review and Meta-Analysis.

MEDLINE and Embase databases were searched between February 2010 and December 2021. All published English articles that report the incidence of VTE stratified by a RAM among patients who underwent plastic surgery were included. The results of the presented meta-analysis were pooled using a random-effects model. The database search revealed 809 articles, out of which eight studies (n = 1,348,606) were eligible. Out of the eight studies, six utilized the Caprini score, and three utilized ASA score. Super-high-risk patients were significantly more likely to present with VTE than their high-risk [odds ratio (OR), 2.92; 95% confidence interval (CI), 1.26-6.78], medium-risk (OR, 5.29; 95% CI, 2.38-11.79), or low-risk counterparts (OR, 10.00; 95% CI, 2.32-43.10) at Caprini score. High-risk patients in ASA score showed significant increase in VTE incidents (OR, 2.72; 95% CI, 1.10-6.72). Both Caprini and ASA RAMs showed compelling evidence of efficacy in our study. However, the Caprini RAM is more predictive of postoperative VTE incidents in high-risk plastic surgery patients than the ASA grading system.

Derivation and External Validation of Clinical Risk Assessment Model for Cancer Associated Thrombosis in Two Unique U.S. Healthcare Systems

Introduction: Venous thromboembolism (VTE), defined as pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a potentially preventable complication for cancer patients undergoing systemic therapy. The Khorana score (KS) is the most used risk assessment model (RAM) to predict venous thromboembolism (VTE) in ambulatory cancer patients. Potential limitations of the score include modest discrimination and small proportion of people developing VTE in the high-risk subgroup. We aimed to derive and externally validate a more precise yet equally RAM for VTE through two unique healthcare systems. Methods: We derived a parsimonious RAM using the cancer registry-linked electronic health records from the Harris Health System (HHS, N=9,916) and validated it using the Veterans Affairs national healthcare system (VA, N=78,892) from 2011-2020. Patients were included if they had their first-ever newly diagnosed cancer and received first-line systemic therapy within 1 year of diagnosis. Index date was the time systemic therapy and all covariates were extracted on or prior to index date. Incident VTE and PE/LE-DVT were defined using our computable phenotype algorithm (PMID: 35647478). When tested against the gold standard of chart abstractor review in a random sampling of 400 patients at each site, the algorithm had a positive predictive value (PPV) of 98% and sensitivity (Sn) of 96% at HHS; and a PPV of 90% and weighted Sn of 82% at VA. For RAM derivation, 34 candidate predictors of VTE were initially chosen by clinicians and 11 final covariates were selected by the LASSO regression via cross-validated optimal lambda.1se. The original KS components were forced into the final model. For external validation, bootstrapped time-dependent c statistics and calibration curves for 6-month VTE and PE/LE-DVT risk were used to assess model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the KS. Complete data analysis was performed without imputation. Results: The median follow-up for continuous VTE assessment were 11.5 months (IQR 5.7-21.1) for HHS and 14.9 months (IQR 5.9-31.9) for VA. At 6 months, there were 656 (6.6%) VTE (including 448 (4.5%) PE/LE-DVT) and 1,094 (11.0%) deaths in HHS, and 3,209 (4.1%) VTE (including 2,474 (3.1%) PE/LE-DVT) and 13,792 (17.5%) deaths in VA. Due to differences in healthcare systems, the two cohorts had very different baseline characteristics in demographic, cancer, systemic therapy, and co-morbidity. Patients from HHS were younger (median age 55 vs. 67), more diverse by sex (female 56.6% vs. 4.9%) and race/ethnicity (15% vs. 71% White, 52% vs. 5% Hispanic, 27% vs. 5% Black, 6% vs. 2% Asian/Pacific Islander [API]), compared to the VA. When assessed at the time of systemic therapy initiation, the new RAM in derivation cohort included components of the KS with modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and API race (Table 1). Due to lower incidence of VTE in VA, re-calibration-in-the-large (intercept only) optimized the overall fit of the model in external validation. The c statistic for the VTE outcome was 0.70 in HHS and 0.66 in VA (compared to 0.64 and 0.59, respectively, for KS). Furthermore, the new RAM appropriately reclassified 27% of patients from the previous risk groups and increased the proportion of VTEs in the high-risk group from 36.7% to 68.0% in the validation dataset (Table 2). Conclusions: Using easily extractable data from two independent healthcare systems, we successfully derived and externally validated a RAM for VTE in a diverse population by sex and race with all cancer types (including hematologic malignancy) and receiving all types of modern systemic therapies (including immune checkpoint inhibitor, targeted therapy, endocrine therapy) in addition to chemotherapy. It stratified approximately 50% of patients with all cancer types receiving all types of modern systemic therapy into a high-risk group with a 6-month VTE risk of 7-11%, and the other half into a low-risk group with a corresponding risk of 3%. The RAM had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. The incorporation of this modified RAM can lead to improved risk stratification and personalized decision-making for pharmacologic thromboprophylaxis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

External Validation of the Saved Score for Venous Thromboembolism Risk Stratification in Patients with Multiple Myeloma Receiving Immunomodulatory Drugs

Background: High thrombogenicity is a well-established phenomenon in multiple myeloma (MM) and can lead to high morbidity and mortality. The risk of venous thromboembolism (VTE) is particularly elevated in the subset of MM patients treated with immunomodulatory drug (IMiD) containing regimens. The National Comprehensive Cancer Network (NCCN) and International Myeloma Working Group (IMWG) have implemented VTE risk assessment models, and recommend prophylactic anticoagulation based on individual patient, disease, or treatment-related factors specifically for MM patients receiving IMiD. With the recent incorporation of the SAVED (PMID 31319391) scoring system in the NCCN guidelines for VTE risk stratification, we sought to externally validate this risk assessment model and evaluate its predictive ability in our MM patient cohort. Methods: We retrospectively evaluated 501 adult patients with either newly diagnosed or relapsed/refractory MM who were newly initiated on an IMiD-based regimen between 2010 and 2019. Patients already on therapeutic or prophylactic anticoagulation were excluded from the study (aspirin was allowed). The SAVED score was calculated at IMiD initiation according to the following five parameters: surgery within last 90 days (+2), Asian race (-3), prior VTE history (+3), age ≥80 years (+1), dexamethasone use (+2 for high dose [>160 mg/30-day], or +1 for standard dose [120-160 mg/30-day]). Patients with SAVED scores of <2 and ≥2 were considered of low and high risk, respectively, for developing VTE after IMiD initiation. Time to VTE was estimated by Kaplan-Meier failure method. Logistic regression model was used to test components of the SAVED score with 1-year VTE status. Model discrimination was assessed via c statistic by calculating the area under the receiver operating characteristic curve (AUC) with bootstrapped 95% confidence interval (CI). Results: The median age of our cohort at the IMiD initiation was 64 years (range 34-89); 264 (53%) patients were male and 378 (75%) were white. IgG and IgA heavy chain subtypes were present in 280 (56%), and 105 (21%) patients respectively, whereas 110 (22%) patients had light chain disease only. The International Staging System (ISS) was I, II, III, and unknown for 161 (32%), 149 (30%), 136 (27%), and 55 (11%) of patients, respectively. Most patients (94%) received lenalidomide, whereas 14 (3%) and 15 (3%) patients were treated with thalidomide and pomalidomide, respectively. The distribution of SAVED covariates is shown in Table 1. The cumulative incidence of VTE at 12-month after IMiD initiation for the entire cohort was 16% (95% CI: 13-20%). Among the 84 patients who developed new VTE after IMiD initiation, 60 (71%) had lower extremity deep venous thrombosis (DVT), 10 (12%) had pulmonary embolism, 9 (11%) had both DVT and PE, and 5 (6%) had upper extremity DVT. The SAVED score stratified 112 patients (22%) as high-risk and 389 patients (78%) as low-risk (similar proportion as the original derivation study). Cumulative incidence of VTE at 6 and 12 months was 31% and 41% in the high-risk group, versus 6% and 9% in the low-risk group, respectively (Figure 1). Each point of SAVED score increase was associated with significantly higher chance of VTE within 1-year post IMiD initiation with excellent discrimination (odds ratio = 2.10 [95% CI 1.71-2.56], c statistic (AUC) = 0.76 [95% CI 0.70-0.81]). Conclusion: Our results successfully externally validated the SAVED model to predict IMiD-associated VTE in a real-life cohort of patients with MM. Patients with SAVED score of ≥2 had significantly higher incidence for VTE. This indicates that more aggressive pharmacologic thromboprophylaxis is needed in this specific patient population. The SAVED score outperformed several other similar VTE prediction models that were also validated in the current cohort (c statistic=0.68 for IMPEDE [PMID: 33997961] and 0.62 for PRISM [PMID: 35772005]). In contrast to other risk models that focused on all patients with MM, the SAVED score was derived and now validated specifically for patients starting IMiD as this it is the only cancer population with a strong guideline recommendation for ambulatory thromboprophylaxis. Future prospective validation would be useful to determine the predictive nature of SAVED while evaluating safety and efficacy of thromboprophylaxis with direct oral anticoagulant in high-risk patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal