Previous History Of Venous Thromboembolism 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...

The impact of venous thromboembolism before open or minimally-invasive radical cystectomy in the USA: insurance claims data on perioperative outcomes and healthcare costs.

The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC). Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined. Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE. Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.

Seek and ye shall find: The utility of perioperative VTE screening in high-risk oncologic patients undergoing abdominopelvic surgery.

The aim of this study was to evaluate the prevalence and risk factors associated with perioperative venous thromboembolism (VTE) in patients undergoing major oncologic surgery using an epidural catheter (EC) for postoperative analgesia with mechanical prophylaxis and without chemoprophylaxis. Six hundred and twenty-sixpatients undergoing major oncologic surgery from 2009 to 2023 were evaluated. VTE was defined as deep vein thrombosis above the level of the knee. Lower extremity venous duplexes (LEVDs) were done preoperatively and postoperatively after the EC was removed. All patients received mechanical thromboprophylaxis, but not chemical prophylaxis, while the EC was in place. A generalized linear multivariable model was constructed to identify risk factors that predict pre and postoperative VTE. 29/626 patients (4.6%) were found to have preoperative VTE. 16/626 (2.6%) were found to have a postoperative VTE when their preoperative LEVD was negative. In comparison to patients without preoperative VTE, those with VTE were more likely to be male, anticoagulated, and have a history of coronary artery disease.Patients in the postoperative VTE group were older, male, anticoagulated, and had a history of VTE. On multivariable analysis, previous history of VTE was the risk factor most strongly associated with both pre and postoperative VTE. Oncologic patients undergoing elective abdominopelvic surgery with epidural analgesia should be screened in the perioperative setting with LEVD to identify VTE and possibly prevent PE.

How to recognize pulmonary embolism in syncope patients: A simple rule

BackgroundSyncope can be the presenting symptom of Pulmonary Embolism (PE). It is not known wether using a standardized algorithm to rule-out PE in all patients with syncope admitted to the Emergency Departments (ED) is of value or can lead to overdiagnosis and overtreatment. MethodsWe tested if simple anamnestic and clinical parameters could be used as a rule to identify patients with syncope and PE in a multicenter observational study. The rule's sensitivity was tested on a cohort of patients that presented to the ED for syncopal episodes caused by PE. The clinical impact of the rule was assessed on a population of consecutive patients admitted for syncope in the ED. ResultsPatients were considered rule-positive in the presence of any of the following: hypotension, tachycardia, peripheral oxygen saturation ≤ 93 % (SpO2), chest pain, dyspnea, recent history of prolonged bed rest, clinical signs of deep vein thrombosis, history of previous venous thrombo-embolism and active neoplastic disease. The sensitivity of the rule was 90.3 % (95 % CI: 74.3 % to 98.0 %). The application of the rule to a population of 217 patients with syncope would have led to a 70 % reduction in the number of subjects needing additional diagnostic tests to exclude PE. ConclusionsMost patients with syncope due to PE present with anamnestic and clinical features indicative of PE diagnosis. A clinical decision rule can be used to identify patients who would benefit from further diagnostic tests to exclude PE, while reducing unnecessary exams that could lead to over-testing and over-diagnosis.

External Validation of PRISM Score in Multiple Myeloma Patients in a Community Setting: A Retrospective Cohort Study

Background: Newly diagnosed Multiple Myeloma (MM) patients have a 10 to 20 times higher risk of developing venous thromboembolism (VTE) than the general population. The pathogenesis may involve several factors such as activation of procoagulant factors, acquired activated protein C resistance, and inflammation. In addition to the general risk factors for venous thromboembolism such as older age, immobility, and surgery, some MM treatment-related factors such as the use of immunomodulatory drug therapy and abnormal cytogenetics contribute to the increased risk. The PRISM score (Prior VTE, Race, IMiD, Surgery, Metaphase Cytogenetics) is a risk prediction tool for VTE in MM and was published in 2022. The score ranges from 0 to 18 and patients were stratified into three groups: low (0), intermediate (1-6), and high risk (≥ 7). Our primary objective was to assess the external validity of the PRISM score in our community hospital setting. Methods: All consecutive newly diagnosed MM treated at Saint Vincent Hospital from 1/1/2008 to 12/22/2022 were included in our analysis. Patients receiving therapeutic anticoagulation for other indications or a diagnosis of VTE within 6 months preceding the MM diagnosis were excluded. Variables were collected through a retrospective chart review during MM treatment initiation. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Logistic regression was used to calculate the odds ratio (OR) of VTE occurrence in the risk prediction model. Results: A total of 214 patients with newly diagnosed MM and available data on VTE occurrence were included. The median age of our cohort at treatment initiation was 74 years (range 31- 96). The median BMI was 27.8. 56% were male, and 44% were female. The mean PRISM score was 2.9, and 73% of MM were IgG/IgA subtype. IMiD-based induction regimen was used in 63 % of patients. A total of 24 patients (11.2%) were diagnosed with VTE after treatment initiation, of which 8 (3.7%) patients had a previous history of VTE. Prophylactic aspirin was used in 53.8% and abnormal metaphase cytogenetics was identified in 13% of MM cases. The median time to VTE from induction therapy was 4.8 months. The PRISM score was low in 116 patients, intermediate in 89, and high in 9 patients. The AUROC of the model was 0.759 (95% CI, 0.644-0.874) (1). The cumulative incidence of VTE at 6 months, 12 months, and more than 1 year was 6%, 7%, and 11.2% of the patients respectively. Each 1-point increase in the score was associated with a significantly higher chance of VTE occurrence in the model [ HR= 1.53, 95% CI (1.27-1.85), P<0.001]. Among the parameters, patients with a history of VTE [ HR= 1.55, 95% CI (1.26-1.91), P<0.001] and with abnormal metaphase cytogenetics [HR= 2.35, 95% CI (1.37-4.05), P<0.001] had a higher strength of association with the development of VTE after induction (2). Furthermore, among 9 patients with a high-risk PRISM score (≥ 7), 7 (77%) developed VTE within the first 6 months after treatment initiation. Conclusions: Our findings suggest that PRISM [AUROC=0.75, 95% CI (0.644-0.874), P<0.001] score could statistically predict VTE outcomes in our patient population. Abnormal metaphase cytogenetics was a significant predictor of VTE in the validation cohort. Abnormal cytogenetics has been well established to be an indicator of aggressive tumor biology and proliferation in stroma-independent MM. It has been established to be a predictor of VTE in acute myeloid leukemia as well. Also, high-risk scores were predictive of earlier development of VTE after treatment induction. Our study strengthens the evidence of using PRISM as a predictive tool. Further studies are needed to enhance the sensitivity of our existing tool.

Comparison of Khorana Vs. Onkotev Predictive Score to Individualize Anticoagulant Prophylaxis in Ambulatory Patients with Cancer

Background: The current guidelines [ J Clin Oncol. 2020;38(5):496] recommend using the risk assessment model (RAM) Khorana score ≥2 [ Blood. 2008;111(10):4902-4907] for primary anticoagulant prophylaxis (PP) of venous thromboembolism (VTE) in patients treated for cancer in an outpatient setting. Recently, a novel RAM, the ONKOTEV score [ JAMA Network Open 2023;6(2):e230010] has been prospectively externally validated with good predictive performance. Like all other established RAMs, the Khorana Score and ONKOTEV models aim to assess the incidence of VTE accurately but do not integrate the expected benefits and potential harms of treatment to determine the clinical utility of the competing management alternatives. We set out to compare the clinical utility of the Khorana Score vs. the ONKOTEV predictive model to guide the PP of VTE in patients receiving anticancer treatment. Methods: We used the ONKOTEV validation dataset (n=425). The ONKOTEV score included the Khorana Score (dichotomized as Khorana score >2 vs. ≤ 2) and three readily available clinical information (also dichotomized): history of previous VTE, the presence of metastatic disease, and clinical or radiological assessment of vascular or lymphatic compression by tumor. After assessing the models' performance (discrimination, calibration), we applied a generalized decision curve analysis (gDCA) to integrate the effects of treatments with the models' predictive accuracy. This, in turn, allowed us to develop individualized recommendations for using PP for VTE in patients receiving anticancer treatment. We calculated net benefits (NB) to compare three management strategies: don't provide any treatment vs. administer prophylaxis to all patients receiving anticancer treatment for VTE vs. use the Khorana or ONKOTEV model to guide PP of VTE. According to gDCA, the best treatment is the one with the highest NB. We obtained data on treatment effects from the meta-analysis of published randomized trials comparing direct oral anticoagulants (DOAC) and low-molecular-weight heparins (LMWH) vs. placebo [ Annals of Palliative Medicine. 2020;9(5):2970]. We estimated that DOAC reduced the risk of VTE by 57% [relative risk reduction (RRR) =0.57 (95%CI: 0.13 to 0.79)] and LMWH by 48% [RRR=0.48 (95%CI: 0.42 to 0.66)]. We assessed the major bleeding rate on DOAC as 0.01 (95%CI: 0.006 to 0.04) and 0.02 (95%CI: 0.01 to 0.03) for LMWH. Results: Both RAMs had a satisfactory performance. Harell's C discrimination statistics was 0.71 for ONKOTEV and 0.66 for Khorana Score with good calibration properties (with intercept and the slope not statistically significantly different from 0 and 1, respectively). Fig 1A shows the results based on the default assumptions: if the patient values avoiding the morbidity of VTE 1.6 to 5 times more (0.2<RV<0.6) than the major bleeding, then offering DOAC to all patients receiving PP for VTE represents the most optimal management strategy. When the patients would rather avoid the consequences of the major bleeding by >2.5x more than the morbidity of VTE, using the ONKOTEV model to guide the administration of DOAC represents the best treatment strategy. If we assume that RRR ≤ 0.2, relying on the ONKOTEV model to guide the use of DOAC becomes the most optimal approach to PP of VTE in patients receiving anticancer treatment (Fig 1B). Conclusion: ONKOTEV model is superior to Khorana Score in guiding individualized PP for VTE in ambulatory patients with cancer. It is particularly helpful when the patient values avoiding major bleeding more than the morbidity of VTE. Our analysis provides new recommendations for PP of VTE receiving outpatient treatment for cancer, calling for updating the current guidelines for PP of VTE in this setting.

Comparative effectiveness of aspirin for symptomatic venous thromboembolism prophylaxis in patients undergoing total joint arthroplasty, a cohort study

BackgroundThis study compares the symptomatic 90-day venous thromboembolism (VTE) rates in patients receiving aspirin to patients receiving low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), after total hip (THA) and total knee arthroplasty (TKA).MethodsData were collected from a multi-centre cohort study, including demographics, confounders and prophylaxis type (aspirin alone, LMWH alone, aspirin and LMWH, and DOACs). The primary outcome was symptomatic 90-day VTE. Secondary outcomes were major bleeding, joint related reoperation and mortality within 90 days. Data were analysed using logistic regression, the Student’s t and Fisher’s exact tests (unadjusted) and multivariable regression (adjusted).ResultsThere were 1867 eligible patients; 365 (20%) received aspirin alone, 762 (41%) LMWH alone, 482 (26%) LMWH and aspirin and 170 (9%) DOAC. The 90-day VTE rate was 2.7%; lowest in the aspirin group (1.6%), compared to 3.6% for LMWH, 2.3% for LMWH and aspirin and 2.4% for DOACs. After adjusted analysis, predictors of VTE were prophylaxis duration < 14 days (OR = 6.7, 95% CI 3.5–13.1, p < 0.001) and history of previous VTE (OR = 2.4, 95% CI 1.1–5.8, p = 0.05). There were no significant differences in the primary or secondary outcomes between prophylaxis groups.ConclusionsAspirin may be suitable for VTE prophylaxis following THA and TKA. The comparatively low unadjusted 90-day VTE rate in the aspirin group may have been due to selective use in lower-risk patients.Trial RegistrationThis study was registered at ClinicalTrials.gov, trial number NCT01899443 (15/07/2013).

Incidence and determinants of venous thromboembolism over 90 days in hospitalized and nonhospitalized patients with COVID-19.

COVID-19 is associated with an increased risk of venous thromboembolism (VTE), but there is great variation among reported incidence rates. Most previous studies have focused on hospitalized patients with COVID-19, and only a few reports are from population-based registries. We studied the 90-day incidence of VTE, associated risk factors and all-cause mortality in hospitalized and nonhospitalized patients with COVID-19 in a nationwide cohort. Data on hospitalizations and outpatient visits were extracted from two national registries with mandatory reporting linked by a unique national identification number carried by all Norwegian residents. We performed Cox proportional hazards regression to determine risk factors for VTE after infection with SARS-CoV-2. Our study included 30,495 patients with positive SARS-CoV-2 polymerase chain reaction with a mean (SD) age of 41.9 (17.3) years, and 53% were males. Only 2081 (6.8%) were hospitalized. The 90-day incidence of VTE was 0.3% (95% CI: 0.21-0.33) overall and 2.9% (95% CI: 2.3-3.7) in hospitalized patients. Age (hazard ratio [HR] 1.28 per decade, 95% CI: 1.11-1.48, p<0.05), history of previous VTE (HR 4.69, 95% CI: 2.34-9.40, p<0.05), and hospitalization for COVID-19 (HR 23.83, 95% CI: 13.48-42.13, p<0.05) were associated with risk of VTE. The 90-day incidence of VTE in hospitalized and nonhospitalized patients with COVID-19 was in the lower end compared with previous reports, with considerably higher rates in hospitalized than nonhospitalized patients. Risk factors for VTE were consistent with previously reported studies.

Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery.

A retrospective cohort study. Venous thromboembolism (VTE) is a potentially high-risk complication for patients undergoing spine surgery. Although guidelines for assessing VTE risk in this population have been established, development of new techniques that target different aspects of the medical history may prove to be of further utility. The goal of this study was to develop a predictive machine learning (ML) model to identify nontraditional risk factors for predicting VTE in spine surgery patients. A cohort of 63 patients was identified who had undergone spine surgery at a single center from 2015 to 2021. Thirty-one patients had a confirmed VTE, while 32 had no VTE. A total of 113 attributes were defined and collected via chart review. Attribute categories included demographics, medications, labs, past medical history, operative history, and VTE diagnosis. The Waikato Environment for Knowledge Analysis (WEKA) software was used in creating and evaluating the ML models. Six classifier models were tested with 10-fold cross-validation and statistically evaluated using t tests. Comparing the predictive ML models to the control model (ZeroR), all predictive models were significantly better than the control model at predicting VTE risk, based on the 113 attributes ( P <0.001). The Random Forest model had the highest accuracy of 88.89% with a positive predictive value of 93.75%. The Simple Logistic algorithm had an accuracy of 84.13% and defined risk attributes to include calcium and phosphate laboratory values, history of cardiac comorbidity, history of previous VTE, anesthesia time, selective serotonin reuptake inhibitor use, antibiotic use, and antihistamine use. The J48 model had an accuracy of 80.95% and it defined hemoglobin laboratory values, anesthesia time, beta-blocker use, dopamine agonist use, history of cancer, and Medicare use as potential VTE risk factors. Further development of these tools may provide high diagnostic value and may guide chemoprophylaxis treatment in this setting of high-risk patients.

Sex-Specific Risk Factors for Deep Venous Thrombosis and Pulmonary Embolism in a Population-Based Historical Cohort Study of Middle-Aged and Older Individuals.

Background Whether sex-specific differences exist for risk factors for pulmonary embolism (PE) and deep venous thrombosis (DVT), with the exception of pregnancy and estrogen therapy, has been sparsely studied. We aimed to study whether sex-specific differences of risk factors exist for noncancer-related DVT and PE in middle-aged and older individuals without cardiovascular history or previous diagnosis in a population-based historical (retrospective) cohort. Methods and Results Potential venous thromboembolism (VTE) risk factors were registered at baseline in 15 807 women and 9996 men aged 44 to 74 years, who participated in the Malmö Diet and Cancer study (1991-1996). We excluded subjects with a previous history of VTE, cancer, a diagnosis of cardiovascular disease, or a diagnosis of cancer-associated VTE during follow-up. Patients were followed up from baseline until the first event of PE or DVT, death, or December 31, 2018. During the follow-up period, 365 (2.3%) women and 168 (1.7%) men were affected by first DVT, and 309 (2.0%) women and 154 (1.5%) men were affected by first PE. In the multivariable Cox regression models, the anthropometric obesity markers of weight, body mass index, waist and hip circumference, fat percentage, and muscle weight were in a dose-dependent way associated with DVT and PE among women but not men. In an analysis that included patients with cardiovascular disease and cancer-related VTE, the results were similar for women. For men, several obesity measures became significantly associated with PE or DVT but were weaker than in women, especially for DVT. Conclusions Anthropometric obesity measures are more important risk factors for both DVT and PE among women than men, especially for individuals without cardiovascular history or previous diagnosis or cancer-related VTE.

A Longitudinal Study of Thrombosis and Bleeding Outcomes With Thromboprophylaxis in Pregnant Women at Intermediate and High Risk of VTE.

The efficacy and safety of thromboprophylaxis in pregnancy at intermediate to high risk of venous thrombo-embolism (VTE) is an area of ongoing research. This study aimed to assess thrombosis and bleeding outcomes associated with thromboprophylaxis in women at risk of VTE. A cohort of 129 pregnancies, who received thromboprophylaxis for the prevention of VTE, were identified from a specialist obstetric clinic in Johannesburg, South Africa. Intermediate-risk pregnancies, with medical comorbidities or multiple low risks, were managed with fixed low-dose enoxaparin antepartum and for a median (interquartile range) of 4 (4) weeks postpartum. High-risk pregnancies, with a history of previous VTE, were managed with anti-Xa adjusted enoxaparin antepartum and for a median of 6 (0) weeks postpartum. Pregnancy-related VTE was objectively confirmed. Major bleeding, clinically relevant nonmajor bleeding (CRNMB) and minor bleeding were defined according to the International Society on Thrombosis and Hemostasis Scientific Subcommittee. Venous thrombo-embolism occurred antepartum in 1.4% (95% CI: 0.04-7.7) of intermediate and 3.4% (95% CI: 0.4-11.7) of high-risk pregnancies. Bleeding events occurred in 7.1% (95% CI: 2.4-15.9) of intermediate and 8.5% (95% CI: 2.8-18.7) of high-risk pregnancies. Of these bleeding events, 3.1% (95% CI: 1.0-8.0) were classified as major bleeding. On univariate analysis, no independent predictors of bleeding were identified. The rates of thrombosis and bleeding in this predominantly African population were consistent with similar studies and can be used to inform pregnant women of the benefits of anticoagulation and the risks of potential bleeding.

Risk of Venous Thromboembolism in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplant

Introduction: Venous thromboembolism (VTE) is a common complication that could affect multiple myeloma (MM) patients. Previous studies suggested the incidence of VTE in MM patients not on VTE prophylaxis to be as high as 10.7% in the peri-transplant period. Usage of antiplatelet or anticoagulant VTE prophylaxis is often a challenging clinical decision especially in patients with profound thrombocytopenia. Here, we aimed to explore the incidence and risk factors for VTE in MM patients undergoing AHCT. Methods: The electronic medical records of all MM patients who underwent AHCT at Cleveland Clinic between January 1st, 2011 and January 15th, 2021 were reviewed. We evaluated the incidence and type of venous thrombosis occurring in the immediate peri-transplant period, defined as extending from the start of stem cell apheresis up to 30 days post-AHCT. Baseline patient, demographic, disease, and transplant factors were evaluated to analyze risk factors for VTE occurrence within the studied period. Statistical Package for Social Sciences (SPSS) was used for statistical analysis. Results: A total of 493 patients with available records were included in our study. The median age was 61.4 years (range 33.1-77.7 years) at the time of AHCT with a male preponderance of 59%. Symptomatic VTE was recorded in 23 events involving 17 patients (3.5%) within the defined peri-transplant period, of which 34.8% of the events occurred between the start of stem cell apheresis and the date of transplant (i.e. day 0). Around 34.8% of VTE events, involving 6 (35.3%), patients occurred during hospitalization for the transplant procedure. All VTEs were non-catheter related, and most were lower extremity deep venous thromboses (DVT) (52.2%), followed by pulmonary emboli (17.4%), DVT of upper extremities (13%), internal jugular thromboses (13%) and superficial vein thrombosis (4.4%). Of the 17 VTE patients, 41% had history of previous VTE prior to the defined peri-transplant period, 88.2% were recently on immunomodulatory drugs (IMiD), 76.5% were on either antiplatelet (41.2%) or anticoagulant (53%) therapy or both (17.7%), while 23.5% were on none. Most of the VTE patients were never smokers (70.6%), while the rest (29.4%) were ex-smokers. Of note, 35.3% of VTE patients had thrombocytopenia (Platelets <150 x109/L) but median platelet count of 184 x109/L. Patients who developed VTE were of similar age (median 62.1 vs 61.4 years, P=0.9) but had a higher female preponderance (64.7 vs 40.1%, P=0.04) compared to those who did not. In addition, they had similar albumin levels at diagnosis (75 vs 71.7% ≥ 3.5 g/dL, P=0.8), similar cytogenetic risk categorization (high risk in 35.3 vs 25.8%, P=0.4), ISS stages (P=0.5), disease remission status prior to AHCT (P=0.3), mobilization regimens (G-CSF + Plerixafor in 88.2 vs 88.2%, P=0.1), and recent IMiD use (88.2 vs76.7, P=0.26) (Table 1). However, VTE patients were more likely to have IgG MM (70.6 vs 62%, P=0.06), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) ≥1 (100 vs 81.1%, P=0.05), infection at AHCT (12.5 vs 3.2%, P=0.05), longer length of AHCT hospital stay (median 17 vs 14.9 days, P<0.0001), and had higher prevalence of prior history of VTE (41.2 vs 11.6%, P<0.0001) (Table 1). With regards to prophylaxis therapy, VTE patients were less likely to be on antiplatelets (41.2 vs 65.6%, P=0.039), were on similar prophylactic anticoagulation (11.8 vs 19.5%, P=0.42), but were more likely to be on therapeutic anticoagulation (41 vs 14%, P=0.002) compared to non-VTE pts, suggesting a higher impact of a history of prior VTE than therapeutic anticoagulation on recurrence of VTE during the studied time period. Among patients with no history of previous VTE, non-VTE patients were more likely to be on either antiplatelet or prophylactic anticoagulation (82.6 vs 50%, P=0.02). Interestingly, no difference was seen in the incidence of VTE with antiplatelet vs prophylactic anticoagulation in patients without history of previous VTE (1.86 vs 0%, P=0.9). Moreover, among those with a history of previous VTE, the addition of antiplatelets to therapeutic anticoagulation did not significantly lower the risk of VTE recurrence in the studied time period (9 vs 16%, P=0.9). Conclusion: The use of VTE prophylaxis among MM patients undergoing AHCT may lower its incidence. The main risk factors for VTE are female sex, history of previous VTE, infections at AHCT, HCT-CI ≥1, and longer hospital stay. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Validation of the Impede VTE Score for Prediction of Venous Thromboembolism in Chinese Patients with Multiple Myeloma: A Retrospective Cohort Study

Background: The risk of venous thromboembolism (VTE) was 9-fold increase in multiple myeloma (MM) compared to the general population. In addition, the mortality rate of MM patients with VTE is three times higher compared to patients without VTE, which makes it so important to identify those at high risk and commit to preventing VTE events. Recently, the IMPEDE VTE score has emerged as a novel risk prediction tool for VTE in MM and has been incorporated and adopted by the NCCN guidelines. The variation in IMPEDE VTE scores is greatly influenced by Asian ethnicity/race, however, it lacks validation, especially for the Chinese populations. Furthermore, the validation of the IMPEDE VTE score's predictive ability for VTE in Caucasian and Black MM is controversial (Blood (2021) 138 (Supplement 1): 2971; Br J Haematol. 2021 Jun;193(6):1213-1219). Therefore, our objective was to validate the predictive ability of the IMPEDE VTE score for VTE in Chinese patients with MM. Methods: We performed a retrospective chart review of all patients with newly diagnosed MM who started chemotherapy at Beijing Jishuitan Hospital between 2011 and 2021 with a minimum of 6 months follow-up. Patients with coexisting tumors, missing data used to calculate VTE scores were excluded. In addition, The SAVED score, simultaneously adopted by the current NCCN Guidelines in risk-stratification of patients with MM receiving IMiD therapy, were analyzed and compared. The scores for IMPEDE VTE and SAVED were calculated from the date of chemotherapy initiation. Statistical analysis included Chi-square, Fisher's test, Wilcoxon rank sum tests, COX hazard, log-rank and K-M survival analysis. A p-value ≤ 0.05 was considered significant and all analysis was completed in SPSS 23.0 and Graphpad Prism version 8.0. Results: Our cohort included 423 newly diagnosed MM patients, 100% Chinese, 221 of whom were male (52.2%) and 141 (33.3%) patients were older than 65 years. Median age and BMI at diagnosis were 60.8 (IQR: 54.0-68.0) years and 24.5 (IQR: 22.2-26.6) kg/m2, respectively. Kaplan Meier survival analysis showed a 5-year survival rate of 53.72%. In the entire cohort, 62 (17.17%) patients developed VTE and 361 patients did not experience VTE within 6 months of treatment onset. The IMPEDE VTE scores at the start of treatment were ≤3 (low risk), 4-7 (moderate risk) and ≥8 (high risk) in 171 (40.43%), 209 (49.41%) and 43 (10.17%) patients, respectively. The median IMPEDE VTE score was 4 (IQR: 2-5) in all patients and 6 (IQR: 4-9) vs. 4 (IQR: 2-5) in the VTE vs. no VTE cohort, respectively (P < 0.001). Patients with MM in the VTE cohort were more likely to have a history of previous VTE (32.3% vs. 3.9％, P < 0.001), paraplegia (9.7% vs. 2.8%, P = 0.011), and extramedullary plasmacytoma (14.5% vs. 4.7%, P = 0.001) compared with no VTE cohort. Within 6 months of treatment initiation, central venous catheter was more frequently used in the VTE cohort as compared to the no VTE cohort (53.2% vs. 20.8%, P < 0.001). The 6-month cumulative incidence of VTE among all patients was 14.7% (95% CI: 11.3%-18%). In univariate Cox hazard analysis, each 1-point increase in IMPEDE VTE score was associated with the occurrence of VTE within 6 months of treatment initiation (HR: 1.33, 95% CI: 1.23-1.44, P < 0.001). According to the IMPEDE VTE score, the 6-month cumulative incidence of VTE was 3.7% (95% CI: 0.1-7.3) , 14.9% (95% CI: 9.9%-20%) and 24.0% (95% CI: 16.3-31.7) in the low-, intermediate- and high-risk groups (P < 0.001, log-rank), respectively (Fig 1A). The c-statistic of the IMPEDE VTE and SAVED scores for predicting VTE within 6 months of treatment initiation was 0.722 (95% CI: 0.647-0.796) and 0.672(95% CI:0.593-0.752), respectively (Fig 1B). The median follow-up of patients was 27.8 months (IQR: 12.1-49.2). On multivariable Cox hazard analysis, VTE within 6 months of treatment initiation was not a predictor of PFS (HR: 0.854, 95% CI: 0.576-1.267, P = 0.434) and OS (HR: 0.853, 95% CI: 0.527-1.379, P = 0.516) after adjusted for age, prognostic stage, cytogenetics, and ASCT. Conclusions: Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM. Both the IMPEDE VTE (P=0.722) and SAVED (P=0.672) scores could statistically predict VTE outcomes in our patient population, and the IMPEDE VTE score outperformed the SAVED score in risk-stratification of Chinese patients with MM treated with IMiD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Strokes in Adult Hospitalized Patients with Sickle Cell Disease and Patients without Sickle Cell Disease: A Nationwide Analysis

Background: Strokes are a common and serious complication of Sickle Cell Disease (SCD). It is the most common cause of stroke in the pediatric population. The risk of recurrent strokes continues into adulthood in SCD population. In this abstract, we quantify the burden of strokes in the SCD population and compare it against the background of strokes in the non-SCD population. Methods: Adult cases with SCD were identified by the International Classification of Disease 10th Revision Diagnosis codes from the National Inpatient Sample Database for 2016-2019. The cases were distributed into age groups based on decades (18-30, 31-40, 41-50, 51-60, 61-70, 71-80; and 81 and above). Cases were identified for the presence of a history of a prior stroke [PMHS] with residual deficits, PMHS without deficits, a new episode of a hemorrhagic stroke, and a new episode of ischemic stroke. Binary logistic regression was performed for multivariate analysis to assess the effect of risk factors that are associated with stroke (age, gender, tobacco use, alcohol, hyperlipidemia [HLD], atrial fibrillation/atrial flutter, hypertension [HTN], peripheral vascular disease [PVD], obesity, diabetes mellitus [for both type 1 and 2], drug use, previous history of venous thromboembolism, and SCD). Please note that "non-SCD” represents only the cases excluding SCD patients. For regression analysis of the "general population", both SCD and non-SCD patients are included. The results are statistically weighted. Results: 431,245 (0.36%) cases with SCD were identified from a total of 120,396,555 cases. The percentages are reported in ascending order of age by decade (18-30, 31-40, 41-50, 51-60, 61-70, 71-80; and 81 and above). The percentages of SCD cases with PMHS without deficits were 8.9, 9.1, 14.5, 8, 13.9, 14.3, and 21.2, respectively, while those for non-SCD cases were 0.3, 0.9, 3.1, 5.2, 7.1, 9.6, and 12.6 respectively. The percentages of SCD cases with PMHS with residual deficit were 1.6, 2.2, 2.8, 3.5, 5.1, 6.4, and 7.2, respectively, while those for non-SCD cases were 0.1, 0.3, 1.3, 2.4, 3.3, 3.7 and 3.7 respectively. The percentages of SCD cases with a new episode of an ischemic stroke were 2, 1.5, 1.9, 2.2, 3.8, 6.1, and 9.6, respectively, while those for non-SCD cases were 0.2, 0.5, 1.5, 2.3, 3.2, 4.3, and 4.7 respectively. The percentages of SCD cases with a new episode of hemorrhagic stroke were 0.1, 0.2, 0.3, 0.6, 0.8, 0.9, and 1.7, respectively, while those for non-SCD cases were 0.1, 0.2, 0.7, 0.8, 0.9, 1, and 1.1 respectively. The comparisons can be seen side by side in Table 1. Upon multivariate analysis of the general population to assess the effect of risk factors on PMHS, the remarkable odds ratios (OR) were: SCD with OR 5.24 (Confidence Interval 5.19-5.29, P<0.001) and HTN 2.19 (2.183-2.192, P<0.001). Multivariate analysis for a new episode of stroke in the general population showed that PMHS had an OR of 2.62 (2.61 - 2.63, P<0.001), HTN 1.745 (1.740-1.751, P<0.001), SCD 1.705 (1.67-1.74, P<0.001) and PVD 1.67 (1.65-1.70, P<0.001). On multivariate analysis for a new episode of stroke in SCD cases, notable results were PMHS with an OR of 7.47 (7.16-7.80, P<0.001), HTN 1.39 (1.32-1.46, P<0.001), HLD 1.58 (1.45-1.71, P<0.001), and tobacco use 1.25 (1.19-1.32, P<0.001). The OR for other risk factors can be reviewed in Table 2. Conclusion: The number of strokes in SCD increases with age. The difference between SCD and non-SCD groups is most pronounced in the younger population. This gap narrows in the fifth decade when the incidence of strokes rises in the general population. PMHS is strongly correlated with new episodes of stroke. Aggressive management of SCD in the younger population, along with optimal risk factor modification (control of diabetes, HTN, HLD, smoking avoidance/cessation) is desirable to decrease the risk of stroke. Further research in this direction is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

229. Using machine learning (ML) models to predict risk of venous thromboembolism (VTE) following spine surgery

229. Using machine learning (ML) models to predict risk of venous thromboembolism (VTE) following spine surgery

Coagulation Abnormalities and Management in Hospitalized Pediatric Patients With COVID-19.

Background:The incidence and severity of coagulation abnormalities have not been extensively studied in pediatric populations with coronavirus disease 2019 (COVID-19). Moreover, their association with an increased risk for thromboembolic events remains unclear, and there is a lack of evidence for optimal prophylactic antithrombotic management. The aim of our study was to present our experience in evaluation, management, and long-term outcomes of coagulation abnormalities in pediatric hospitalized patients with COVID-19.Methods:A prospective study was performed in all children hospitalized for COVID-19 during a 6-month period focusing on patients’ coagulation abnormalities, the normalization of the coagulation profile with or without anticoagulation prophylaxis and the clinical outcome of the disease.Results:Two hundred twenty-three patients (median age: 11.4 months) were enrolled in the study. Coagulation abnormalities were detected in 92.4% of patients with increased D-dimer levels to be the most common abnormality detected in 84.3% of patients. Prophylactic anticoagulation was initiated only in 7 (3.1%) selected patients with severe COVID-19 and at least 2 risk factors for venous thromboembolism (VTE) and in all patients with previous history of VTE. Follow-up coagulation profile in 85 patients showed that changes over time had a tendency towards normalization irrespectively of the initiation of anticoagulant thromboprophylaxis. No thrombotic complications were observed 3 months upon discharge.Conclusions:Although abnormal findings in coagulation profile were very common, they were not associated with risk for VTE even in severe cases. A trend of normalization early in the course of the disease was observed regardless of the use of anticoagulant thromboprophylaxis.

Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism?

SummaryWe examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60–79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow‐up period of 18 years, there were 149 confirmed cases of fatal or non‐fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D‐dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D‐dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C‐reactive protein or interleukin‐6. The combination of D‐dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.

Hereditary Thrombophilia Testing Among Hospitalized Patients: Is It Warranted?

BackgroundHereditary thrombophilias (HTs) are a group of inherited disorders that predispose the carrier to venous thromboembolism (VTE). It is estimated that 7% of the population has some form of HT. Although testing for HT has become routine for many hospitalized patients, knowing when to order the tests and how to interpret the results remains challenging. In the United States, there are no clear guidelines regarding testing for HT. We conducted a study to evaluate the utilization of HT testing among hospitalized patients to examine its impact on immediate management decisions and overall cost burden. In addition, we discuss the common reasons for healthcare providers to order these tests and review the data behind these reasons in the literature.MethodologyA retrospective analysis of 2,402 patients who underwent HT testing between February 1, 2016, and January 31, 2018, was conducted. Eligible patients had at least one HT test ordered during hospitalization. The primary outcome was to determine the incidence of positive actionable tests. A positive actionable test was defined as a positive result that changed the anticoagulation intensity, type, or duration. Patients with a history of previous VTE, ongoing medical conditions requiring life-long anticoagulation, or unprovoked VTE were considered non-actionable.ResultsAmong the 2,402 patients, 954 patients met the inclusion criteria with a mean age of 54 years. A total of 397 (41.6%) tests were ordered for acute VTE, while the rest were for non-VTE conditions, such as stroke, pregnancy complications, peripheral artery diseases, and others. Only 89 positive tests were actionable (14% of the positive tests, and 9.3% of the total ordered tests). There was a statistically significant association between increasing age and having both a positive test result (p = 0.006) and an actionable test (p = 0.046). The total cost of ordering these tests was estimated to be $566,585.ConclusionsHT testing in the inpatient setting did not alter management in many cases and was associated with increased healthcare costs. The decision to order these tests should be individualized based on the clinical scenario.

Recurrent VTE in Pregnant Woman with Previous Personal History of VTE: A Systematic Review and Meta-Analysis

Introduction: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality during pregnancy and the postpartum periods. Despite that, the prevention and management of VTEs in pregnant patients remains an area of great debate, particularly among those with a personal VTE history. There is no solid evidence behind the current practice guidelines on the prevention of VTE in pregnancy as most data comes from studies focusing on non-pregnant patients or from small studies. It has been suggested that without low molecular weight heparin (LMWH) thromboprophylaxis, women with a personal history of VTE may have a 2% to 10% absolute risk of developing recurrent VTE during a subsequent pregnancy. We conducted a systematic review to evaluate the risk of VTE recurrence during pregnancy for pregnant patients with prior personal history of VTE and the effect of LMWH on such risk.Materials and Methods: MEDLINE and EMBASE were searched between January 2000 to December 2020. We included studies that evaluated pregnant patients with previous personal VTE history (deep vein thrombosis (DVT) and pulmonary embolism (PE) only) that assessed venous thromboembolism recurrence and/or bleeding complication and/or pregnancy outcomes. Study selection and data extraction was conducted by 3 reviewers and discrepancies resolved by consensus. A meta-analysis of proportions was done through a Freeman-Tukey transformation using random effect models. Groups were analyzed according to prophylaxis strategy. Heterogeneity between studies was assessed by Cochrane Q and Higgins I 2 analyses. Publication bias was assessed using Eggers' tests and funnel plot.Results. Of 6934 potential studies, 27 were included in this systematic review. The studies included 3631 pregnant patients with a previous history of DVT or PE, regardless of the presence of thrombophilia. We found a wide variability in thromboprophylaxis practices which included mostly low molecular weight heparin using weight-based, risk category-based, anti-Xa based, fixed, or trimester-adjusted doses . In studies that categorized patients into provoked, estrogen associated and unprovoked, most patients had an estrogen-associated previous VTE.The estimated pooled proportions of VTE recurrence were 2.7% (95% CI 1.8-3.7; I 2 55.5%) in patients who were consistently on anticoagulation during pregnancy (pre- and post-partum), 2.6% (95% CI 0.6-5.9; I 2 not estimable) in patients who received anticoagulation in the postpartum period only, and 25.3% (95% CI 8.9-46.6; I 2 93.2%) in patients who were not on anticoagulation. No comparison could be done on the different dosage strategies due to the limited number of studies and wide variety of strategies. Due to limited data available, bleeding complications and pregnancy outcomes could not be assessed.Conclusion. In patients with a previous VTE history receiving prophylactic anticoagulation (either both pre- and post-partum or post-partum only), the estimates of VTE recurrence were significantly lower than that for patients who did not receive prophylaxis, however, a direct comparison was not possible. The optimal thromboprophylaxis strategy remains unknown. DisclosuresNo relevant conflicts of interest to declare.

Venous Thromboembolism Post-COVID-19 Among Individuals with Sickle Cell Disease

Background: Individuals with sickle cell disease (SCD) are at risk of severe COVID-19 infection. Those with SCD are also known to be at risk of venous thromboembolism (VTE), with numerous mechanistic pathways likely at interplay. In general, prior studies indicate that COVID-19 infection is associated with a thromboembolic risk. However, it is unknown if COVID-19 infection increases the already high risk of VTE for individuals with SCD. Given the preexisting risk for thrombophilia associated with SCD, we hypothesized that COVID-19 infection would further increase the risk of a venous thromboembolic event. In this study, we leverage electronic health record data to determine, at a population level, whether individuals with SCD hospitalized for COVID-19 have higher VTE rates when compared to hospitalization for any other cause.Method: Using electronic health record data from a multisite research network, TriNetX (years 2010 - 2020) we identified two mutually exclusive cohorts of individuals with SCD between Jan 20, 2020 - Dec 31, 2020: 1) those with hospitalizations related to a diagnosis of COVID-19 and 2) those with hospitalization for other causes. COVID-19 related hospitalizations were defined as admissions occurring within a month of COVID-19 diagnosis. Overall, individuals were considered to have SCD if they had 3 or more instances of ICD coding for SCD during the time frame of years 2010 - May 20, 2021 and did not have any ICD code for sickle cell trait. The outcome of interest was VTE, which included either deep venous thrombosis (DVT), pulmonary embolism (PE) or both. We determined the VTE rates at 1 month, 3 months and 6 months post hospitalization. The VTE rates between the two groups were compared using measures of risk difference and risk ratios, along with the respective 95% confidence intervals. We also matched the groups using propensity scores based on the prevalence of VTE prior to the index event of hospitalization and compared the respective outcomes.Results: Within the TriNetX network, there were 223 (59% females) individuals with SCD hospitalized due to COVID-19, and 3,591 (54% females) hospitalized for causes other than COVID-19. Individuals with SCD hospitalized for COVID-19 were older than individuals with SCD hospitalized for other causes (mean age: 29.4 yrs, sd = 16.4 vs 26.3 yrs, sd = 16.8, p value = 0.006). A significantly higher proportion of individuals hospitalized for COVID-19 had a prior history of portal vein thrombosis (4% vs ~0%, p-value <0.001), phlebitis/thrombophlebitis (4% vs 2%, p-value = 0.026) and other VTE (16% vs 10%, p-value = 0.008). There were no significant differences in sex or proportion of those with prior history of PE between the two groups. Table 1 shows the VTE rates observed in the two groups 1, 3 and 6 months post-hospitalization, respectively. VTE rates were higher among individuals with SCD hospitalized for COVID-19 than among individuals with SCD hospitalized for other causes. After matching for previous history of VTE, individuals with SCD hospitalized for COVID-19 infection did not have significantly higher VTE rates compared to individuals with SCD hospitalized for other causes at any of the time points evaluated.Conclusions: These data suggest that immunothrombosis accompanying SARS-COV-2 infection in individuals with SCD does not exacerbate the underlying known thrombophilia associated with SCD and provide support for current clinical guidelines in this population. Future prospective studies controlled for anticoagulant therapy exposures may provide more direct evidence to guide thromboprophylaxis in this unique population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.