Thromboprophylaxis Strategies Research Articles

Thromboprophylaxis with intermediate dose enoxaparin during asparaginase containing induction for young adults with acute lymphoblastic leukemia

Thrombosis rates among young adults receiving asparaginase (ASP) for acute lymphoblastic leukemia (ALL) can reach 34%, with highest risk during induction. Our institution implemented a standard practice of 1 mg/kg/day enoxaparin administered to young adults with ALL who are treated with ASP during induction. We performed a retrospective analysis of patients who received thromboprophylaxis with enoxaparin 1 mg/kg/day during ASP-containing induction for ALL at Oregon Health & Science University from 2012 to 2023. The primary outcome was the cumulative incidence of thrombosis during induction. Bleeding events were assessed. Sixty-two patients were included in our analysis. Four patients (6.5%; 95% CI 1.8%-15.7%) experienced a thrombotic event. Three events were catheter-associated and 1 event was a distal lower extremity deep vein thrombosis related to myositis. No cerebral sinus thromboses, thrombosis-related deaths or major bleeding events occurred. Intermediate-dose enoxaparin is a promising thromboprophylaxis strategy and warrants further prospective research.

A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Antithrombin III Levels and Outcomes Among Patients With Trauma

Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma. To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma. This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024. The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality. The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT. In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

Risks of major bleeding and venous thromboembolism in patients undergoing total hip or total knee arthroplasty using therapeutic dosages of DOACs.

About 1.5% of patients undergoing total hip (THA) or total knee arthroplasty (TKA) still develop postoperative venous thromboembolism (VTE), indicating that the current thromboprophylaxis strategy is not optimal. To evaluate the feasibility of therapeutic dosages of direct oral anticoagulants (DOACs) as thromboprophylaxis for high VTE risk patients, we determined the risks of major bleeding and VTE in patients who underwent THA/TKA and were treated with DOACs in therapeutic dosages for atrial fibrillation (AF). We conducted a registry-based cohort study from 2010 to 2018 in Denmark and included AF patients on therapeutic DOACs dose who underwent THA/TKA. AF patients were utilized as proxy since they have a life-long indication for therapeutic anticoagulant medication. The 49-days cumulative incidence (with death as competing risk) of major bleeding was assessed. The same was done for VTE at 49- and 90-days. 1,354 THA and TKA procedures were included. The 49-days cumulative incidence of major bleeding was 1.40% (95%Confidence Interval[CI] 0.88-2.14%). Most bleeding events occurred at the surgical site. The cumulative incidence of VTE at 49-days was 0.59% (95%CI 0.28-1.13%) and 0.74% (95%CI 0.38-1.32%) at 90-days. The incidence of major bleeding in THA/TKA patients on DOACs in therapeutic dosages was in line with previously reported incidences among THA/TKA patients on thromboprophylaxis dosages, while the incidence of VTE was relatively low. These data provide a solid basis for the design of randomized controlled trials to establish the safety and efficacy of therapeutic dosages of DOACs to prevent VTE in high-risk patients.

Deep vein thrombosis: Implications of thromboprophylaxis after lower limb cast immobilisation.

Deep vein thrombosis is a recognised complication of lower limb cast immobilisation and post operative state immobilisation. A national survey revealed that low molecular weight heparin (LMWH) is the favoured strategy for thromboprophylaxis in the latter context. However, clinicians need to be aware of the fact that the use of LMWH might incur the risk of subsequent development of heparin-induced thrombocytopenia, with its attendant life-threatening thrombotic complications. Some of the patients who develop those complications might be admitted under the care of general physicians, hence the importance of raising awareness of this issue.

Monitoring anti-Xa levels in elderly medical patients undergoing thromboprophylaxis: A prospective cohort study.

Given the rising incidence of venous thromboembolism (VTE) and insufficient thromboprophylaxis dosing evidence in certain patients, the precise monitoring of anti-Xa (aFXa) levels is crucial. The aim of this study is to investigate the achievement of prophylactic aFXa levels in medical inpatients who were receiving parenteral anticoagulant and to evaluate the impact of various factors on aFXa levels. This is a single-center observational cohort study conducted on patients admitted to the Department of Internal Medicine at the University Hospital of Heraklion, Greece, from March to August 2023. These individuals received low-molecular-weight heparins thromboprophylaxis owing to an increased risk of VTE. Data regarding demographics, past medical history, and somatometric and laboratory findings were recorded. The established range for peak prophylactic aFXa levels was defined as 0.2-0.5 IU/mL. In this study, we enrolled 150 individuals [91 (60.7%) women] with a mean age of 80.0 ± 14.1 years. Sixty-two (41.4%) patients exhibited non-prophylactic peak aFXa levels. Supratherapeutic levels were observed in all underweight patients and subtherapeutic levels in 12 of 13 obese patients in class II and III. A multivariate linear regression analysis revealed that body weight, cancer, and the Charlson Comorbidity Index (CCI) were independent factors influencing aFXa levels. Our study reveals a substantial portion of medical elderly inpatients on thromboprophylaxis with non-prophylactic aFXa levels, with a notable prevalence among underweight and severely obese patients. Body weight, cancer, and CCI were identified as independent factors influencing aFXa levels, advocating for tailored thromboprophylaxis strategies. Further research is warranted to validate personalized dosing approaches and to enhance clinical decision-making. Geriatr Gerontol Int 2024; 24: 587-594.

Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey.

Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non–Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study

BackgroundVenous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non–small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. Materials and MethodsA nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen–Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. ResultsAmong the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. ConclusionVTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Appropriate thromboprophylaxis strategy for COVID-19 patients on dosage, antiplatelet therapy, outpatient and post-discharge prophylaxis: a meta-analysis of randomized controlled trials.

There was controversy surrounding the optimal thromboprophylaxis strategy for COVID-19 patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and post-discharge. To explore this, we performed a meta-analysis of randomized controlled trials. PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet and post-discharge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. Our study included a total of 25 randomized controlled trials, involving 17,911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95%CI, 0.45 to 0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For non-critically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95%CI 0.34 to 0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95%CI 1.22 to 3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95%CI 0.21 to 0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For post-discharge patients, post-discharge prophylaxis reduced thromboembolism risk (RR, 0.49; 95%CI 0.31 to 0.76) but increased major bleeding risk (RR, 2.63; 95%CI, 1.13 to 6.14). For non-critically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and post-discharge patients, required further investigation and confirmation through rigorous evidence studies.

Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study

BackgroundThis study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures.MethodsThe retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals.ResultsThe overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment.ConclusionsPatients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.

Effectiveness and cost effectiveness of pharmacological thromboprophylaxis for medical inpatients: decision analysis modelling study

ObjectiveTo determine the balance of costs, risks, and benefits for different thromboprophylaxis strategies for medical patients during hospital admission.DesignDecision analysis modelling study.SettingNHS hospitals in England.PopulationEligible adult medical inpatients, excluding patients...

Estimating the value of future research into thromboprophylaxis for women during pregnancy and after delivery: a value of information analysis

BackgroundRisk assessment models (RAMs) are used to select women at increased risk of venous thromboembolism (VTE) during pregnancy and the puerperium for thromboprophylaxis. ObjectivesTo estimate the value of potential future studies that would reduce the decision uncertainty associated with offering thromboprophylaxis according to available RAMs in the following groups: high-risk antepartum women (eg, prior VTE), unselected postpartum women, and postpartum women with risk factors (obesity or cesarean delivery). MethodsA decision-analytic model was developed to simulate clinical outcomes, lifetime costs, and quality-adjusted life-years for different thromboprophylaxis strategies, including thromboprophylaxis for all, thromboprophylaxis for none, and RAM-based thromboprophylaxis. The expected value of perfect information analysis was used to determine which factors are associated with high decision uncertainty. The value of future research studies was estimated using expected value of sample information analysis. Costs were assessed from a health and social services perspective. ResultsThe expected value of perfect information analysis identified high decision uncertainty for high-risk antepartum women (£21.8 million) and obese postpartum women (£13.4 million), which was largely attributable to uncertainty regarding the effectiveness of thromboprophylaxis in reducing VTE. A randomized controlled trial of thromboprophylaxis compared with none in obese postpartum women is likely to have substantial value (£2.8 million; 300 participants per arm). A trial in women with previous VTE would have higher value but would be less acceptable. ConclusionFuture research should focus on estimating the effectiveness of thromboprophylaxis in obese postpartum women with additional risk factors who have not had a previous VTE.

Enoxaparin for VTE thromboprophylaxis during inpatient rehabilitation care: assessment of the standard fixed dosing regimen

BackgroundWe aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation.MethodsThis was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity.ResultsWe found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients’ weight and renal function as defined by creatinine clearance (CrCl) (p<0.05).ConclusionsOur study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function.Trial registrationNo. NCT103593291, registered August 2018.

Venous thromboembolism prophylaxis and multiple myeloma patients in real-life: Results of a large survey and clinical guidance recommendations from the IFM group

Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio.

Venous Thromboembolism in Total Hip and Total Knee Arthroplasty

The optimal pharmacologic thromboprophylaxis agent after total hip and total knee arthroplasty is uncertain and consensus is lacking. Quantifying the risk of postoperative venous thromboembolism (VTE) and bleeding and evaluating comparative effectiveness and safety of the thromboprophylaxis strategies can inform care. To quantify risk factors for postoperative VTE and bleeding and compare patient outcomes among pharmacological thromboprophylaxis agents used after total hip and knee arthroplasty. This retrospective cohort study used data from a large health care claims database. Participants included patients in the United States with hip or knee arthroplasty and continuous insurance enrollment 3 months prior to and following their surgical procedure. Patients were excluded if they received anticoagulation before surgery, received no postsurgical pharmacological thromboprophylaxis, or had multiple postsurgery thromboprophylactic agents. In a propensity-matched analysis, patients receiving a direct oral anticoagulant (DOAC) were matched with those receiving aspirin. Aspirin, apixaban, rivaroxaban, enoxaparin, or warfarin. The primary outcome was 30-day cumulative incidence of postdischarge VTE. Other outcomes included postdischarge bleeding. Among 29 264 patients included in the final cohort, 17 040 (58.2%) were female, 27 897 (95.2%) had inpatient admissions with median (IQR) length of stay of 2 (1-2) days, 10 948 (37.4%) underwent total hip arthroplasty, 18 316 (62.6%) underwent total knee arthroplasty; and median (IQR) age was 59 (55-63) years. At 30 days, cumulative incidence of VTE was 1.19% (95% CI, 1.06%-1.32%) and cumulative incidence of bleeding was 3.43% (95% CI, 3.22%-3.64%). In the multivariate analysis, leading risk factors associated with increased VTE risk included prior VTE history (odds ratio [OR], 5.94 [95% CI, 4.29-8.24]), a hereditary hypercoagulable state (OR, 2.64 [95% CI, 1.32-5.28]), knee arthroplasty (OR, 1.65 [95% CI, 1.29-2.10]), and male sex (OR, 1.34 [95% CI, 1.08-1.67]). In a propensity-matched cohort of 7844 DOAC-aspirin pairs, there was no significant difference in the risk of VTE in the first 30 days after the surgical procedure (OR, 1.14 [95% CI, 0.82-1.59]), but postoperative bleeding was more frequent in patients receiving DOACs (OR, 1.36 [95% CI, 1.13-1.62]). In this cohort study of patients who underwent total hip or total knee arthroplasty, underlying patient risk factors, but not choice of aspirin or DOAC, were associated with postsurgical VTE. Postoperative bleeding rates were lower in patients prescribed aspirin. These results suggest that thromboprophylaxis strategies should be patient-centric and tailored to individual risk of thrombosis and bleeding.

Machine Learning to Predict Risk of Venous Thromboembolism Among Patients with Myeloproliferative Neoplasms in the Intensive Care Unit

INTRODUCTION Myeloproliferative neoplasms (MPN) increase the risk of venous thromboembolism (VTE) and constitute important thrombotic risk factors. VTE risk is especially high if these patients require the intensive care unit (ICU). Precise and user-friendly diagnostic tools that incorporate complex interactions between clinical data and laboratory results to predict VTE among patients with MPN in the ICU are lacking. We hypothesize that machine-learning algorithms could be used to predict VTE and guide thromboprophylaxis in this population. METHODS This was an observational, retrospective study using routine clinical practice data from MIMIC-IV, a freely accessible electronic health record database. We analyzed patients with an MPN diagnosis who were admitted to the ICU. ICD-9 and ICD-10 codes were utilized to identify incident VTE events during ICU stay (I82X, 453X). Descriptive statistics were reported for all variables of interest. Various machine-learning models were utilized to predict the incident VTE as the outcome variable. Patients who had expired as discharge dispositions were excluded. Models accounted for demographic characteristics, laboratory results, comorbidity burden, and other domains. Model performance was evaluated by comparing the accuracy and Area Under the Receiver Operating Characteristic Curve (AUROC) values. RESULTS We analyzed 378 cases that met the inclusion criteria. Among these, 160 (42.3%) were female. The majority were White (65.9%), and 151 (39.9%) had Medicare insurance. The median [Q1, Q3] age of the sample was 64.0 [52.2, 76.8] years. VTE occurred in 27 patients (7.1% incidence). ICU mortality was reported in 26 (6.9%) cases. The proportion of ER admissions was 48.1% among those cases who had VTE and 47.6% among those who didn't have VTE in the ICU (p &amp;gt; 0.05). Patients who developed VTE were more likely males (66.7% vs. 33.3%), but there was no difference in age (median age 61 vs. 64 years; p &amp;gt; 0.05). The machine learning model results showed that the Naive Bayes classifier performed best in predicting VTE in the ICU among patients with MPNs, with an AUROC value of 84.36%, followed by the deep learning model, with an AUROC value of 68.3%. The deep learning model showed that the top ten variables associated with VTE by feature importance were oxygen saturation, length of stay, blood urea nitrogen, other insurance type, anion gap, respiratory rate, bicarbonate, pressure of oxygen, pH value, and race other than White. CONCLUSION Predicting VTE in the ICU among patients with MPNs may be achieved by machine learning methods. The deep learning algorithm outperformed other models in terms of discrimination and calibration. If validated and applied in clinical practice, these methods may optimize thromboprophylaxis strategies. Future research is needed to test this model in more extensive clinical settings.

High Rates of Thrombotic Events in Newly Diagnosed Multiple Myeloma Patients Enrolled on the Maia Trial

Background. Patients with newly diagnosed multiple myeloma (NDMM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Despite the availability of the IMWG and NCCN VTE prophylaxis guidelines and updated risk stratification models such as SAVED and IMPEDE, the optimal thromboprophylaxis strategy is unknown, especially in the age of modern daratumumab-containing regimens. To continue highlighting the importance of appropriate thromboprophylaxis for patients with NDMM, we performed a post-hoc analysis of the randomized phase 3 MAIA trial to identify rates of venous and arterial thromboembolism. Methods. This retrospective study, carried out under YODA Project #2021-4663, used data from the randomized phase 3 MAIA trial that investigated lenalidomide and dexamethasone (Rd) with or without daratumumab (DRd) in 733 transplant ineligible (TIE) patients obtained from the Yale University Open Data Access (YODA) Project, which has an agreement with JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C.. Thrombotic events (TE), including both venous and arterial events (V/ATE) were examined with VTE events including deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial thrombophlebitis (SVT). Arterial events (ATE) included cerebrovascular accidents (CVA) defined as hemorrhagic, ischemic, or verebrobasilar strokes. The incidence and time to event of V/ATE were calculated and graded using the CTCAE v4, with Grade 1 representing nonactionable venous thrombosis, Grades 2-4 representing TEs requiring increasing higher levels of medical intervention, and Grade 5 indicating death was a result of the TE. Rates and time to events were compared between the DRd and Rd arms. Results. Of the included patients, median age was 72 years (range 64-72) and 48% were female. There was no signficant difference between baseline characteristics of sex, race, myeloma subtype, presence of high-risk cytogenetics, or ISS staging between patients that experienced a V/ATE event and those that did not. All grade V/ATE events were 18% (66/363) and 19% (70/365) in the DRd and Rd arms, respectively. Of these, most were VTE events in both arms (16%), with G2-4 actionable VTE event rate of 14.9% vs 14.8% for the DRd and Rd arms, respectively. G5 VTE events were 0.2% in both arms (no G5 ATEs). ATE were 2.2% and 2.7% in the DRd and Rd group, respectively, overall constituting a minority of events. The overall PE rate was higher in the DRd than Rd arm, 6.3% vs 4.7%, DVT was more frequent in the Rd arm, 9.6% vs 7.7%, and rates of SVT rates were similar between both arms at 1.9% and 2.2% for the DRd vs Rd arms, respectively (Table 1). Median time to onset of cumulative TEs was longer in DRd vs Rd arm, 7.15 (0.27 - 63.0) vs 4.65 (0.03 - 58.0) months, respectively. Among these, median time to onset of VTE was similar among the groups [6.57 (0.27 - 63.0) vs 4.48 (0.03 - 52.9) months, respectively] while the median time to onset of ATEs was longer in DRd vs Rd arm, 19.8 (1.70 - 26.6) vs 8.3 (0.67 - 58.5) months. The incidence of VTE events persisted past 24 months and incidence of ATE events increased over time (Figure 1). Analysis regarding prophylactic anticoagulation use and rates of TE based on prophylactic regimen are ongoing. Conclusion. This retrospective study reveals the highest reported rates of VTE in any modern therapy dataset. In patients with transplant ineligible NDMM, we show that the TE risk persists past 24 months of treatment in patients on DRd or Rd therapy. Similar to observations in the GRIFFIN trial, the addition of daratumumab did not increase the risk of TE. Our report highlights the critical need for further investigation of optimal prophylactic strategies and their duration for patients with NDMM.

Anticoagulant prophylaxis in pregnant women with a history of venous thromboembolism: A systematic review and meta-analysis

BackgroundVenous thromboembolism (VTE) remains one of the leading causes of morbidity and mortality during pregnancy and the postpartum period. Despite that, the prevention and management of VTEs in pregnant patients is an area of great debate. ObjectivesThe aim of this systematic review was 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. MethodsMEDLINE and EMBASE were searched between January 2000 to December 2022. We included studies that evaluated pregnant patients with previous personal history of VTE and assessed VTE recurrence with or without thromboprophylaxis. A meta-analysis of proportions was done through a Freeman–Tukey transformation using random effect models. Results30 studies were included in this systematic review. The studies included 5075 pregnant patients with a previous history of DVT or PE. We found a wide variability in thromboprophylaxis strategies. The estimated pooled proportions of VTE recurrence were 2.5% (95% CI 1.8–3.3) in patients who were consistently on anticoagulation during pregnancy (pre- and post-partum), 4.7% (95% CI 1.8–8.8) in patients who received anticoagulation in the postpartum period only, and 13.6% (95% CI 6.5 to 22.8) in patients who were not on anticoagulation. ConclusionsIn 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 lower than for patients who did not receive prophylaxis, however, a direct comparison was not possible. The optimal thromboprophylaxis strategy remains unknown.

PB1476 Occurrence of Hospital-Associated Thrombosis Despite Thromboprophylaxis in the Setting of Current Thromboprophylaxis Strategies: An Observational Cross-Sectional Study

PB1476 Occurrence of Hospital-Associated Thrombosis Despite Thromboprophylaxis in the Setting of Current Thromboprophylaxis Strategies: An Observational Cross-Sectional Study

Adiposity and Coagulation: Predicting Postinjury Coagulation With Advanced Imaging Analysis

IntroductionAnatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. MethodsSegmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. ResultsData from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). ConclusionsSP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.