Prior History Of Venous Thromboembolism Research Articles

Incidence and Potentially Modifiable Risk Factors for Venous Thromboemblism Post Lung Transplant

Venous thromboembolism (VTE) is a frequent complication after lung transplantation. Most VTE occur within 30 days of surgery and consist primarily of upper extremity deep venous thrombosis (DVT). Prior studies have described incidence rates of up to 43%, which is much higher than in other solid organ transplantation. VTE after lung transplantation has been associated with a lower survival post-transplant. Due to the morbidity and costs incurred by this complication, modifiable post-operative risk factors must be identified to improve our outcomes after lung transplantation. Retrospective study population of patients who received a lung transplant at Temple University Hospital, Philadelphia, between 2017 and 2018 (n=197). We collected baseline demographics, laboratory values, intra-operative variables, as well as post-operative care measures such as central line days, pulmonary artery catheter days, days to physical therapy, initiation timing and interruptions in pharmacologic prophylaxis. The primary outcome was VTE event within one year of lung transplantation. 197 lung transplants were performed (R: 73 L: 70, double: 54) with a mean age of 65.5 years, most common indications were IPF (53%) and COPD (32.5%). The incidence of VTE within one year of transplant was 23.5% (n=47), most of which occurred within 30 days of transplant (72%). Most patients had upper extremity DVT (55%) and was treated with systemic anticoagulation (83%). Patients who had VTE after transplant tended to have a higher BMI (p=0.0048) and oxygen requirement (p=0.028) pre-operatively. Patients with VTE had a longer duration of Swan-Ganz catheter (p=0.0145) and the introducer catheter (p=0.0092). VTE patients had a longer time to physical therapy (p=0.06) and time to ambulation (p=0.0471) post-surgery. On multivariate analysis, interruptions in pharmacologic VTE prophylaxis within the first five days post-operatively was the only modifiable risk factor identified (OR, 4.123, % CI, 1.642-10.352, p=<0.0001). Unlike previous studies, we did not find an association between VTE post-transplant and a history of prior VTE, LAS score, diabetes, or age. Any interruption in DVT prophylaxis early post-transplant is a significant "modifiable" risk factor for development of VTE. Every effort should thus be made to avoid any interruption in prophylaxis.

Prediction of Symptomatic Venous Thromboembolism in Critically Ill Patients: The ICU-Venous Thromboembolism Score.

To identify risk factors and develop a prediction score for in-hospital symptomatic venous thromboembolism in critically ill patients. Retrospective cohort study. Henry Ford Health System, a five-hospital system including 18 ICUs. We obtained data from the electronic medical record of all adult patients admitted to any ICU (total 264 beds) between January 2015 and March 2018. None. Symptomatic venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both, diagnosed greater than 24 hours after ICU admission and confirmed by ultrasound, CT, or nuclear medicine imaging. A prediction score (the ICU-Venous Thromboembolism score) was derived from independent risk factors identified using multivariable logistic regression. Of 37,050 patients who met the eligibility criteria, 529 patients (1.4%) developed symptomatic venous thromboembolism. The ICU-Venous Thromboembolism score consists of six independent predictors: central venous catheterization (5 points), immobilization greater than or equal to 4 days (4 points), prior history of venous thromboembolism (4 points), mechanical ventilation (2 points), lowest hemoglobin during hospitalization greater than or equal to 9 g/dL (2 points), and platelet count at admission greater than 250,000/μL (1 point). Patients with a score of 0-8 (76% of the sample) had a low (0.3%) risk of venous thromboembolism; those with a score of 9-14 (22%) had an intermediate (3.6%) risk of venous thromboembolism (hazard ratio, 6.7; 95% CI, 5.3-8.4); and those with a score of 15-18 (2%) had a high (17.7%) risk of venous thromboembolism (hazard ratio, 28.1; 95% CI, 21.7-36.5). The overall C-statistic of the model was 0.87 (95% CI, 0.85-0.88). Clinically diagnosed symptomatic venous thromboembolism occurred in 1.4% of this large population of ICU patients with high adherence to chemoprophylaxis. Central venous catheterization and immobilization are potentially modifiable risk factors for venous thromboembolism. The ICU-Venous Thromboembolism score can identify patients at increased risk for venous thromboembolism.

Administrative codes inaccurately identify recurrent venous thromboembolism: The CVRN VTE study

BackgroundStudies using administrative data commonly rely on diagnosis codes to identify venous thromboembolism (VTE) events. Our objective was to assess the validity of using International Classification of Disease, 9th Revision (ICD-9) codes in identifying recurrent VTE. Materials and methodsAmong 5497 adults with confirmed incident VTE from four healthcare delivery systems in the Cardiovascular Research Network (CVRN), we identified all subsequent inpatient, emergency department (ED), and ambulatory clinical encounters associated with an ICD-9 code for VTE (combined with relevant radiology procedure codes for inpatient/ED VTE codes in the secondary discharge position or outpatient codes) during the follow-up period. Medical records were reviewed using standardized diagnostic criteria to assess for the presence of new, recurrent VTE. The positive predictive value (PPV) of codes was calculated as the number of valid events divided by total encounters. ResultsWe identified 2397 encounters that were considered potential recurrent VTE by ICD-9 codes. However, only 31.1% (95%CI: 29.3–33.0%) of encounters were verified by reviewers as true recurrent VTE. Hospital or ED encounters with VTE codes in the primary position were more likely to represent valid recurrent VTE (PPV 61.3%, 95%CI: 56.7–66.3%) than codes in secondary positions (PPV 35.4%, 95%CI: 31.9–39.3%), or outpatient codes (PPV 20.3%, 95%CI: 18.3–22.5%). PPV was low for all VTE types (29.9% for pulmonary embolism, 38.3% for lower and 37.7% for upper extremity deep venous thrombosis, and 14.1% for other VTE). ConclusionsICD-9 codes do not accurately identify new VTE events in patients with a prior history of VTE.

The risk and prevention of venous thromboembolism in the pregnant traveller.

The average risk of venous thromboembolism (VTE) in long haul travellers is approximately 2.8 per 1000 travellers, which is increased in the presence of other VTE risk factors. In pregnant long-haul travellers, little is known in terms of the absolute risk of VTE in these women and, therefore, there is limited consensus on appropriate thromboprophylaxis in this setting. This review will provide guidance to allow practitioners to safely minimize the risk of travel-related VTE in pregnant women. The suggestions provided are based on limited data, extrapolated risk estimates of VTE in pregnant travellers and recommendations from published guidelines. We found that the absolute VTE risk per flight appears to be <1% for the average pregnant or postpartum traveller. In pregnant travellers with a prior history of VTE, a potent thrombophilia or strong antepartum risk factors (e.g. combination of obesity and immobility), the risk of VTE with travel appears to be >1%. Postpartum, the risk of VTE with travel may be >1% for women with thrombophilias (particularly in those with a family history) and other transient risk factors and in women with a prior VTE. Based on our findings, we recommend simple measures be taken by all pregnant travellers, such as frequent ambulation, hydration and calf exercises. In those at an intermediate risk, we suggest a consideration of 20-30mmHg compression stockings. In the highest risk group, we suggest careful consideration for low-molecular-weight heparin thromboprophylaxis. If there are specific concerns, we advise consultation with a thrombosis expert at the nearest local centre.

D-Dimer As a Prognostic Biomarker for Venous Thromboembolism after Hematopoietic Cell Transplantation

Introduction: D-dimer has been well characterized as a prognostic biomarker for venous thromboembolism (VTE) in both the general population and cancer patients. However, it is unclear if D-dimer has prognostic value after hematopoietic transplantation (HCT) in the context of regimen-related toxicity, immune dysregulation, and infectious complications. In the current study, we examined the utility of biomarkers of coagulation activation and fibrinolysis (D-dimer, PAI-1, and TPA) as prognostic and diagnostic biomarkers for VTE post-transplant. Methods: We performed a prospective cohort study of adult allogeneic or autologous HCT recipients over 4 years at the Fred Hutchinson Cancer Research Center. Plasma samples were collected weekly from pre-transplant to discharge from HCT. Plasma samples were rapidly thawed and concentrations of D-dimer, PAI-1 activity, and TPA antigens were tested by commercially available immunoassays. VTE was defined as radiology confirmed pulmonary embolism (PE), lower extremity (LE) or upper extremity (UE) deep vein thrombosis (DVT) within 1 year after the date of transplant. This outcome was abstracted through a combination of ICD codes and individual patient record review. Cumulative incidence was estimated using the Kaplan Meier failure method. We used the Cox regression model to determine the association between baseline biomarkers and the development of VTE. The prediction accuracy of the model was assessed by the Harrell's C statistic. To explore the utility of D-dimer testing post-transplant, we selected all patients that had clinical suspicion for VTE, underwent radiographic evaluation (chest computed tomography or compression ultrasound), and had available sample for D-dimer testing within a two-week window. We defined the age-adjusted threshold as 500 ng/mL if at or below age 50 and 10 times the age if above age 50. We also repeated the analysis using a higher cut-off of 1000 ng/mL. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were generated from the 2x2 table. Results: We identified 112 HCT adult recipients (97 allogeneic and 15 autologous) who were enrolled in the prospective cohort study and provided baseline plasma samples for biomarker testing. Patients had a mean age of 48, were predominately male and white, and had acute myeloid leukemia (AML) as the most common diagnosis (Table 1). Approximately 8% (9 patients) had a history of prior VTE. During the 1-year follow-up period, a total of 8 patients developed VTE (3 PE, 3 LE-DVT, 2 UE-DVT) with a cumulative incidence of 11.8% (5.8-23.2) by 12 months. There was no association between baseline TPA and PAI-1 and VTE; however, baseline D-dimer was associated with VTE with a HR of 1.91 (p=0.007) in the unadjusted model and a HR of 1.95 (p=0.007) in the model adjusted for history of VTE (Table 2). The predictive model with baseline D-dimer and history of VTE had a Harrell's C statistic of 0.75 for discrimination. For the exploratory analysis of the D-dimer post-transplant, we used a subset of 21 patients that had clinical suspicion of VTE, radiology confirmation, and available plasma sample for D-dimer testing. The sensitivity and NPV for both age-adjusted cut-off and 1000 ng/mL were 100%; however, the sample size was small (Table 3). Conclusions: In this cohort study, we found that baseline D-dimer, but not PAI-1 or TPA, was associated with the development of VTE during the first-year post-transplant. A multivariable model with D-dimer and history of VTE had a modest discrimination for VTE prediction. Similar to many clinical settings, D-dimer testing post-transplant may aid clinicians with prediction and diagnosis of VTE. Larger cohort is needed for validation of the findings. Disclosures No relevant conflicts of interest to declare.

High Rates of Venous and Arterial Thrombotic Events in POEMS Patients: Results from the UK-Based POEMS Registry, Highlighting the Need for Therapeutic Guidelines

Introduction Arterial and venous events are known to occur in patients with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome which may also include myeloproliferation, with a reported rate in the literature of around 20%. This is higher than in the myeloma cohort where the VTE rate from the UK Myeloma XI study was reported as 11.8%. The approach to optimum management of thrombosis in POEMS patients remains undefined. Method The UCLH POEMS Registry is a comprehensive tertiary centre-based UK data repository including patients from 1999 to the present. Data were collated from patients referred in for diagnosis or after treatment and included blood results, neurological and general performance status, previous and active venous thromboembolism (VTE) and arterial events and their management. Results Of the 103 patients in the UCLH POEMS Registry, 20 were excluded due to missing data. Of the 83 patients included, median age was 52 years (31-84) and 54 (65%) were male. Mean haemoglobin at diagnosis was 143 g/L (89-190), platelet count 443 x10^9 (194-741), vascular endothelial growth factor (VEGF) 3536 pg/mL (388-15422), creatinine 75 μmol/L (32-168) and albumin 40 g/L (31-50). Performance status was ≥ 3 in 15 patients. Radiotherapy was used as a treatment modality in 21/83 (25%) and 48/83 (52%) patients received autografts. There were 51 outpatient-based chemotherapy regimens prescribed. Lenalidomide and dexamethasone (LD) was the most common prescription 30/51 (59%), followed by cyclophosphamide and dexamethasone in 10/51 (20%), LD plus cyclophosphamide in 3/51 (6%), melphalan and steroids 3/51 (6%), cyclophosphamide, dexamethasone and thalidomide 2/51 (4%), LD plus ixazomib 1/51 (2%), velcade, thalidomide and dexamethasone 1/51 (2%) and carfilzomib with dexamethasone 1/51 (2%). Of these 51 outpatient-based chemotherapy scripts, 30 received documented thromboprophylaxis (TP). Prophylactic low molecular weight heparin (pLMWH) was prescribed most frequently (17/30) with 16 of these patients receiving an immunomodulatory based chemotherapy regimen. Other TP agents used include: aspirin (6/30), treatment dose LMWH (tLMWH) (2/30), rivaroxaban (2/30), warfarin (2/30) and clopidogrel (1/30). Twenty-five patients experienced a total of 35 clinically apparent arterial or venous events. Seven had more than 1 thrombotic event, 2 of which developed both arterial and venous thromboses. Three patients had a prior history of VTE;1 with historic DVT developed pulmonary emboli, and 2 had arterial events after historic VTE. Eleven patients had 14 VTEs including DVT (6/14), PE (4/14) and 4 PICC-associated DVT occurring during melphalan-based autograft. Most VTEs occurred during active disease with median VEGF 2731 (444-5000). Five venous events occurred on chemotherapy, including 4 during a melphalan-based autograft, and 1 on LD. VTE occurred despite prophylactic LMWH in 3 patients (2 unknown). Treatment comprised LMWH (4), warfarin (4), or the direct oral anticoagulants, rivaroxaban (1) and apixaban (1). One patient did not receive treatment for a PICC-associated DVT. Sixteen patients experienced 21 arterial events including stroke (7/21), peripheral vascular disease (6/21), MI (4/21) and microvascular disease (2/21). Most events occurred during active disease with median VEGF 3155 (637-10640). Three occurred on anti-POEMS therapy: one patient (VEGF 4555) developed a second stroke on LD and LMWH prophylaxis; one patient on LD (VEGF 10640) and prophylactic rivaroxaban 10mg developed PVD, and another on melphalan and prednisolone (VEGF 2000-4000) and warfarin for atrial fibrillation (target INR 2.0-3.0) developed PVD. Conclusion The venous and arterial event rate in this cohort at 35/83 (42%) is over double that previously reported. There were more arterial events than venous, and most occurred in a state of active disease and off anti-POEMS therapy (26/35), suggesting that treatment-related risk factors are less of a driver for thrombosis than the disease itself. There was no discernible relationship with thrombocytosis. Thromboprophylaxis is commonly used in POEMS patients receiving outpatient-based chemotherapy with the most common agent being prophylactic LMWH. With the high incidence of arterial events in the presence of active disease, the role for anti-platelet agents or indeed DOACs remains undefined in this patient group. Disclosures Thomas: Sanofi: Membership on an entity's Board of Directors or advisory committees. D'Sa:Janssen: Honoraria, Research Funding.

Risk Factors for Pediatric Cerebral Sinovenous Thrombosis: A Case-Control Study with Pediatric Neuroradiologist Case Validation

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) is a rare but serious disease process among all patients, with a slightly higher prevalence in pediatric patients. Despite its low frequency, CSVT represents the second most common type of venous thromboembolism (VTE) in children, next to deep vein thrombosis (DVT) of the limbs. Current literature lacks robust evidence on risk factors for CSVT, especially in the pediatric population. We sought to determine risk factors of CSVT in pediatric patients, via a single-institutional case-control study. METHODS: A case-control study was conducted at Johns Hopkins All Children's Hospital from patients admitted between March 31st 2006 and April 1st 2018. Cases were identified based on ICD-9 and ICD-10 codes and confirmed via electronic medical record (EMR) review and neuroradiologist confirmation of radiologic testing. Two controls were then randomly selected for each CSVT case, matched by month and year of admission. Clinical and demographic parameters were collected via abstraction from the EMR, including: age at admission, prior history of VTE, previous hospitalization within 30 days, head/neck surgery, other major surgery, congenital or acquired heart disease, dehydration, cancer, serious infection (included meningitis, sepsis, pneumonia, osteomyelitis, fungemia, pyelonephritis, head/neck infection, abscess involving anatomic sites other than skin or head/neck), prematurity, mechanical ventilation, chronic inflammatory disease, cystic fibrosis, nephrotic syndrome, obesity, and head/neck trauma. Associations between CSVT and putative risk factors were evaluated via logistic regression, using odds ratios (ORs) and 95% confidence intervals (95%CIs). Those risk factors with P-values &lt;0.1 in univariate logistic regression were included in adjusted (multivariate) logistic regression modeling; results of the latter employed a threshold of P&lt;0.05 for statistical significance. RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (and interquartile range in) age was 4.79 years (0.02-13.56 years) for cases and 5.58 years (1.16-10.78 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: presence of central venous catheter; serious infection; mechanical ventilation; chronic inflammatory disease; and head/neck trauma. In the multivariate model, mechanical ventilation (OR=9.01, 95%CI=2.19-37.02) and head/neck trauma (OR=11.52, 95% CI=2.63-50.41) remained independent, statistically-significant risk factors for CSVT. CONCLUSIONS: This single-institutional case-control study reveals that mechanical ventilation and head/neck trauma are independent risk factors for pediatric CSVT. These findings will be further investigated via the multicenter Children's Hospital-Acquired Thrombosis (CHAT) registry dataset, by which a risk model for CSVT in children will be further developed and validated, in order to inform future preventive strategies in pediatric patients at heightened risk of CSVT. Table Disclosures Goldenberg: NIH: Other: research support and salary support.

Extended Mutational Profiling By MSK-IMPACTTM Identifies Mutations Predicting Thromboembolic Risk in Patients with Solid Tumor Malignancy

Background: Cancer-associated thrombosis (CAT) is a leading cause of death in cancer patients after cancer itself. Risk factors for CAT include tumor type/stage, body mass index (BMI), blood cell counts and chemotherapy exposure. These factors form the basis of prediction algorithms for CAT risk, including most notably the Khorana Risk Score. However, significant limitations exist with these currently-available risk prediction models. Emerging data suggest that a tumor's molecular profile can impact venous thromboembolism (VTE) risk. Mutations of ALK, EGFR, IDH1, ROS1, and KRAS for example have been shown to modulate the risk of CAT; however, these studies were limited by the number of mutations and specific tumor types analyzed. We hypothesized that extended molecular testing in a large patient cohort would allow for improved detection of molecular signatures associated with CAT. We analyzed deep-coverage targeted sequencing data (up to 341 genes) of tumor samples from 11,776 cancer patients to identify gene mutations associated with VTE. Methods: Adult patients with any solid tumor diagnosis who had their tumors sequenced using MSK-IMPACT from 1/2014 to 12/2016 were retrospectively assessed for CAT events using redundant algorithmic methods and individual chart reviews. The endpoint was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis (DVT). An episode of upper extremity DVT was considered a competing event. The observation period was limited to 365 days after IMPACT blood control sampling. Cause-specific Cox proportional hazards regression was used to test for an association between gene and CAT risk, adjusting for clinical covariates including age, cancer type, cytotoxic chemotherapy (time-dependent), anticoagulant use, stage (metastatic/non-metastatic) and prior history of VTE. Separate multivariate models evaluated the association for the 60 most frequently-mutated genes identified, along with ALK, MET, ROS1 which were included based on existing literature suggesting an effect on VTE risk. Final p-values were adjusted for false discovery using the Benjamini-Hochberg procedure, and the threshold for statistical significance was set at 0.10. Patients with multiple cancer diagnoses were excluded. Results: Out of 11,776 individuals we observed 727 CAT events (6.2% of cohort). The most commonly represented tumor types were lung (18%), breast (15%) and colorectal cancer (10%); see Figure for a breakdown of CAT incidence by tumor type. Most (72%) of patients were metastatic at time of IMPACT testing and 4% were on anticoagulation therapy. Statistically significant predictors of CAT included cytotoxic chemotherapy (HR 1.61 [1.37-1.9]; p&amp;lt;0.001), history of VTE preceding cancer diagnosis (HR 2.48 [1.62-3.79]; p&amp;lt;0.001), and presence of metastatic disease (HR 2.48 [1.94-3.16]; p&amp;lt;0.001). Molecular profiling of tumors revealed STK11 (HR 1.93 [1.42-2.64]; adjusted p=0.002), KRAS (HR 1.42 [1.17-1.72]; adjusted p=0.012), KEAP1 (HR 1.78 [1.18-2.69]; adjusted p=0.095), and MET (HR 1.8 [1.17-2.78]; adjusted p=0.095) somatic mutations were associated with a significant increase in the risk of CAT, independent of tumor type. However, it should be noted that a majority of these genes were specific to lung cancer highlighting the prevalence of this tumor type within the IMPACT cohort. Additionally, the presence of IDH1 mutations in primary brain tumors correlated with a decreased risk of CAT in comparison to wild-type IDH1 (HR 0.34 [0.16-0.69]; adjusted p=0.068), consistent with previous studies. See Table for an extended report of regression coefficients. Conclusions: This work is the first large-scale analysis to elucidate cancer-specific genomic determinants of CAT. Using a large patient cohort, we found that somatic tumor mutations in STK11, KRAS, IDH1, KEAP1, and MET modulate the risk of venous thromboembolism in solid tumor patients. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types. We hope these findings will ultimately translate into improved risk stratification for patients at risk of CAT. Disclosures Mones: Janssen: Research Funding. Iyengar:Puma Biotechnology: Consultancy; Novartis: Consultancy. Hyman:AstraZeneca: Consultancy, Research Funding; Fount: Consultancy, Equity Ownership; Pfizer: Consultancy; Chugai Pharma: Consultancy; Loxo Oncology: Research Funding; Boehringer Ingelheim: Consultancy; Bayer Pharmaceuticals: Consultancy, Research Funding; Genentech / Roche: Consultancy; PUMA Biotechnology: Research Funding; CytomX Therapeutics: Consultancy. Park:Merck: Research Funding; Parker Institute for Cancer Immunotherapy: Research Funding; Astellas: Research Funding; Ipsen: Consultancy. Khorana:Bayer: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy. Soff:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Mantha:Medical Case Management Group: Consultancy; MJH Live Events: Other: Give CME talk; Heidell, Pittoni, Murphy &amp; Bach, LLP: Consultancy; Daboia Consulting LLC: Equity Ownership; Janssen: Research Funding.

Potential Overuse of Primary Thromboprophylaxis in Medical Inpatients at Low Risk of Venous Thromboembolism

Background: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in the United States. Annually, up to 1 in 120 people develop VTE, approximating the incidence of stroke. Given that hospitalization and acute medical illness increase the risk of VTE, hospital-associated VTE represents a preventable cause of morbidity and mortality. Accordingly, accreditation and regulatory agencies endorse inpatient pharmacologic VTE prophylaxis (PPX) as a quality measure. In order to raise rates of PPX prescribing, many health systems have adopted a default approach to electronic ordering, in which clinicians must "opt-out" of PPX prescription. However, this strategy may cause medical overuse and avoidable harms, which has prompted the American Society of Hematology (ASH) to recommend a risk-adapted approach to PPX. One risk model endorsed by ASH is the IMPROVE-VTE risk assessment model, which can identify patients who are at low risk for VTE and therefore may not warrant pharmacologic PPX. We therefore sought to compare the actual practice of PPX prescribing to the guideline-recommended strategy according the IMPROVE-VTE model in a large, contemporary population of medical inpatients. Methods: In this observational study, we used electronic health record data to identify adult, medical inpatients hospitalized on general medical and subspecialty services at Yale-New Haven Hospital from 1/1/14-12/31/18. We excluded patients who were pregnant, admitted for VTE, taking full dose anticoagulation on admission, admitted for bleeding, or had a platelet count of &lt; 50,000/µL. For each patient, we calculated the IMPROVE-VTE score using the previously validated model weights: 3 points for a prior history of VTE; 2 points for known thrombophilia, lower limb paralysis, or active cancer; 1 point for immobilization, admission to the intensive care unit, or age ≥ 60 years. For each component other than age, we used ICD-9 and ICD-10 codes that were billed either prior to or upon admission to determine the presence of these risk factors. In order to simulate the decision to initiate PPX on hospital admission, we calculated each patient's IMPROVE-VTE score at the time of admission. In accordance with the ASH guidelines, we used an IMPROVE-VTE score of &lt;2 to differentiate patients at low-risk of hospital-associated VTE from those at high-risk. We used inpatient medication order history data to determine receipt of pharmacologic PPX. We used χ2 testing to compare the relative frequency of PPX prescribing on admission between patients at low-risk and high-risk for VTE. Results: We identified 135,288 medical inpatients during the study period, of whom 99,380 met inclusion criteria. The average age was 63.5 years-old (standard deviation 18 years); 51% of patients were female; 68% of patients were white. Of all the included patients, 81% received pharmacologic prophylaxis; of these patients, 78% received unfractionated heparin subcutaneously and 22% received low molecular weight heparin subcutaneously. Among all hospitalized patients, 78% had an IMPROVE-VTE score of &lt;2 (32% had a score of 0 and 46% had a score of 1). Among these patients at low risk of hospital-associated VTE, 81% received pharmacologic PPX. Differences in prophylaxis rates between patients at low vs high risk of VTE were statistically significant (p&lt;0.001). Conclusion: In this contemporary cohort of adult, medical inpatients, &gt;80% of patients who were at low risk of hospital-associated VTE received pharmacologic PPX, representing a group in whom PPX may be unnecessary. Using a risk-adapted approach such as the IMPROVE-VTE risk assessment model, rather than default PPX ordering, may reduce medical overuse and avoidable harms. Disclosures Chaudhry: CVS State of CT Clinical Pharmacy Program: Other: Paid Reviewer for CVS State of CT Clinical Pharmacy Program.

Symptomatic Thromboembolic Complications After Shoulder Arthroplasty: An Update.

Venous thromboembolism (VTE) complications, including deep vein thrombosis and pulmonary embolism, are dreaded complications of orthopaedic surgical procedures that can result in substantial morbidity and mortality. There is a paucity of data examining risk factors for VTE in shoulder arthroplasty. The purpose of the present study was to review the rate of symptomatic VTE, determine patient and operative risk factors for VTE, and report on complications associated with VTE following shoulder arthroplasty. Over a 16-year period, 5,906 patients underwent primary anatomic total shoulder arthroplasty, reverse total shoulder arthroplasty, or hemiarthroplasty. Symptomatic VTE events were identified in 24 shoulders within 90 days of surgery. Patient records were reviewed for surgical indication, patient and operative risk factors, and management of VTE. The rate of symptomatic VTE following shoulder arthroplasty was 0.41%. There were no deaths resulting from VTE events. Compared with patients who did not have VTE, those with symptomatic VTE events were found to be older (74.75 versus 68.51 years; p = 0.0028) and more likely to have had arthroplasty for a traumatic indication (3.31% versus 0.33%; p < 0.001). Age of >70 years and arthroplasty for a traumatic indication were found to be independent risk factors on multivariate nominal logistic regression analysis, whereas body mass index, sex, operative time, and type of arthroplasty performed were not found to be independent risk factors. There were 11 readmissions resulting directly from the VTE events, and patients diagnosed with VTE as inpatients had longer hospital stays than outpatients (13.71 versus 1.94 days; p = 0.0002). The risk of VTE following shoulder arthroplasty is low, and routine use of pharmacologic VTE prophylaxis may not be necessary. However, VTE complications can lead to substantial morbidity, longer hospital stays, readmission to the hospital, and further complications. Therefore, patients with multiple risk factors for VTE such as prior history of VTE, active malignancy, age of >70 years, or arthroplasty for traumatic indications should be considered for pharmacologic VTE prophylaxis. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

57 Risk of Venous Thromboembolism in Acute Necrotizing Pancreatitis: A Population-Based National Study

INTRODUCTION: Studies on the incidence of venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism (PE), in patients with acute pancreatitis (AP) with or without necrosis are scarce. We conducted a population-based national study to evaluate the incidence of VTE and PE in patients with AP using a large database. METHODS: Data were extracted from a large database which incorporates 26 major integrated healthcare systems and over 300 hospitals in the United States (Explorys, Cleveland, OH). Using Systematized Nomenclature of Medicine (SNOMED) codes we identified patients with a diagnosis of acute pancreatitis with and without necrosis in the year 2018. The primary outcome was the incidence of index (first-ever) VTE at 7-days after diagnosis of AP. Patients with a prior history of VTE were excluded. Secondary outcomes included rates of sepsis, mechanical ventilation, intensive care unit admission, acute kidney injury, need for dialysis, and all-cause mortality. Univariate analysis was performed; P value &lt; 0.05 was considered statistically significant. RESULTS: A total of 10,840 cases of acute necrotizing pancreatitis (ANP) and 65,960 cases of AP without necrosis were identified. Cohort demographics and outcomes are shown in Table 1. At 7 days after onset of ANP, VTE occurred at a rate of 18.5%, compared with 5.9% in AP without necrosis (OR 2.75, 95% CI 2.64–2.87, P &lt; 0.01), while PE occurred at a rate of 2.3% in ANP vs. 0.4% in AP without necrosis (OR 6.2, 95% CI 5.20–7.41, P &lt; 0.01) (Figure 1). In the setting of ANP, VTE was associated with a significantly higher all-cause mortality (follow-up 121–485 days) (OR 1.54, 95% CI 1.36–1.73, P &lt; 0.01). In ANP cohort, univariate analysis demonstrated significantly higher associations of VTE with baseline smoking, alcohol consumption, and elevated BMI. Secondary outcomes including sepsis, intensive care unit admission, mechanical ventilation, acute kidney injury, and the need for dialysis, were all significantly associated with the development of VTE in ANP (Table 1). CONCLUSION: Patients with ANP have a near 3-fold risk of VTE, and a 6-fold risk of PE, compared to those with AP without necrosis. The development of VTE in the setting of ANP is associated with higher all-cause mortality. This study was unable to assess whether early pharmacologic VTE prophylaxis would improve outcomes. A large prospective study would aid in investigating the effect of this intervention.

Association of blood group and red blood cell transfusion with the incidence of antepartum, peripartum and postpartum venous thromboembolism

The increased risk of venous thromboembolism (VTE) associated with pregnancy is well-known and prophylaxis guidelines consider a number of risk factors. Although non-O blood group and red blood cell (RBC) transfusion are known to be associated with VTE risk, their contribution to pregnancy-associated VTE has received little attention. This study was conducted in a population-based cohort of 1,000,997 deliveries to women with no prior history of VTE or thrombophilia. The independent contributions of ABO blood type and RBC transfusion to the risks of antepartum, peripartum and postpartum VTE are reported as odds ratios adjusted for risk factors that are considered in current prophylaxis guidelines and other potential confounders. Compared with type O, A and B blood types have higher risk of antepartum and postpartum VTE, with odds ratios between 1.4 and 1.8. Transfusion around delivery has the largest increased risks and a dose-response effect, with adjusted odds ratios from 2.60 (1.71–3.97) for 1–2 units to 3.55 (1.32–9.55) for more than 5 units. ABO blood type and RBC transfusion were found to be independent risk factors for pregnancy-associated VTE. Further research is required to understand the underlying mechanisms and to conduct a risk-benefit assessment of the small volumes of RBCs transfused around delivery.

Peripherally Inserted Central Catheters Lead to a High Risk of Venous Thromboembolism in Children

Background: The incidence of venous thromboembolism (VTE) in children has seen a sharp increase in recent years with the majority of cases secondary to central venous catheters (CVCs). Among CVCs, the number of peripherally inserted central catheters (PICCs) placed in children has risen significantly. Methods: In this multi-center, prospective, observational cohort study, we enrolled patients aged 6 months to 18 years with newly placed PICCs or tunneled lines (TLs) and compared the incidence of VTE between them. We also evaluated the incidence and risk factors of CVC-related VTE, central line associated bloodstream infections (CLABSIs) and catheter malfunctions in PICCs and TLs. Findings: A total of 1967 CVCs placed in 1742 unique subjects were included in the analysis. The incidence of catheter-related VTE was 5.9±0.63%. The majority of the cases, 80%, were in subjects with PICCs which had a significantly higher risk of catheter-related VTE than subjects with TLs (HR=8.5, 95%CI, 3.1-23, p<0.001). PICCs were also significantly more likely to have a CLABSI (HR=1.6, 95%CI: 1.2-2.2, p=0.002) and CVC malfunction (HR=2.0, 95%CI: 1.6-2.4, p<0.001) compared to TLs. Increased risk of CVC-related VTE was found in patients with a prior history of VTE (HR=23, 95%CI: 4-127, p<0.001), multi-lumen CVC (HR=3.9, 95%CI: 1.8-8.9, p=0.003) and leukemia (HR=3.5, 95%CI: 1.3-9.0, p=0.031). Interpretation: Children with PICCs had a significantly higher incidence of catheter-related VTE, CLABSI and CVC malfunction over TLs. The results suggest that pause be taken prior to placing a CVC, especially PICCs, due to the serious complications they have been shown to cause. Funding Statement: The authors state: there was no funding source for this study. Declaration of Interests: The authors declare that they do not have any conflicts of interest. Ethics Approval Statement: This study was approved by the ethics committee at each participating institution.

Safety profile of midline catheters in patients with active malignancy.

e18046 Background: Patients with malignancy often require a safe and reliable intravascular access for disease management along the spectrum of diagnosis to end-of-life care. Despite a growing interest on the use of midlines, there is a scarcity of data on their safety in cancer patients. Data from observational studies suggest a lower rate of thrombotic and infectious complications when compared to peripherally-inserted central catheters (PICCs). However, there are no formal recommendations tailored to oncologic patients on when to prefer one type of vascular access versus another. Methods: We retrospectively gathered data from all midline catheters inserted in patients with active cancer at our institution from January 2016 to June 2017, totaling 159 procedures. Our primary analysis sought to determine the incidence of venous thromboembolism (VTE), CRBSI and bleeding. Results: Out of a total of 159 procedures performed in patients with solid tumor and hematologic malignancies, chemotherapy infusion was the indication in 17 (10.69%), with difficult intravenous access being the indication in 97 patients (61%) and prolonged antibiotic therapy in 44 patients (27.6%). Only one patient got a midline for peripheral parenteral nutrition. The mean dwell time of midline catheters was 9.4 days. A total of 5 patients (3.14%) developed catheter-associated thromboembolic episodes. All of them had metastatic solid tumors. No events were reported in patients with hematologic malignancies. Of note, 2 of these 5 patients had a prior history of VTE. The number of days from device insertion to VTE ranged from 2-14 days, with an average of 9.5 days. Catheter-related infection occurred in 1 patient (0.62% or 0.66 per 1000 catheter-days). No bleeding complications were reported. Conclusions: Midline catheters appear to be a safe and cost-effective alternative for secure vascular access, especially in patients with non-metastatic solid tumors and hematologic malignancies. Caution and close monitoring for occurrence of VTE are advised for those with high metastatic burden and prior history of VTE. The rate of infectious complications are low, which is in concordance with previous literature.

Comparison of pharmacologic prophylaxis in prevention of venous thromboembolism following total knee arthroplasty

BackgroundAnticoagulants are used following total knee arthroplasty (TKA) to prevent venous thromboembolism (VTE). These drugs reduce VTE risk but may lead to bleeding-related complications. Recently, surgeons have advocated using antiplatelet agents including aspirin (ASA). However, there is no consensus regarding which medication has the optimal risk/benefit profile. The purpose of this study was to compare rates of VTE using different anticoagulants in anticoagulation-naïve patients being discharged home after TKA. MethodsA national private insurance database was used to identify patients undergoing unilateral TKA. Patients with a prior history of VTE were excluded. Anticoagulants included ASA, low molecular weight heparin (LMWH), warfarin, factor Xa inhibitors (XaI), and fondaparinux. Postoperative complications, including VTE, blood transfusion, myocardial infarction, and hematoma, were identified using ICD-9 diagnosis codes. Risk of each complication was compared between groups using multivariate logistic regression controlling for demographics, length of stay, and comorbidities. ResultsOf 30,813 patients, 1.82% were diagnosed with VTE. Using ASA as a baseline, there was significantly decreased risk of VTE with LMWH (OR 0.47), XaI (OR 0.50), and fondaparinux (OR 0.32). There was significantly higher risk of transfusion with LMWH (OR 1.56) and fondaparinux (OR 1.84), but no difference in hematoma between medications. ConclusionsThis study shows that there is a decreased risk of VTE with LMWH, XaI, and fondaparinux compared to ASA. However, these medications also had higher rates of bleeding-associated complications. The choice of pharmacologic prophylaxis should be made based on a balance of the risk/benefit profile of each medication. Level of evidenceIII.

Improving Rates of Venous Thromboembolism Prophylaxis in Multiple Myeloma Patients on Immunomodulatory Drugs

BACKGROUND: Multiple myeloma patients who receive immunomodulatory drugs (IMiDs: lenalidomide, thalidomide, and pomalidomide) have an increased risk of developing venous thromboembolism (VTE). Guidelines for thromboprophylaxis are based on additional patient and disease characteristics. We describe our single-institution experience with VTE prophylaxis and an intervention to improve VTE risk assessment and prophylaxis.METHODS: A retrospective review using an internal patient database assessed VTE in multiple myeloma patients being treated with IMiDs from 2000-2016. VTE risk factors for each patient were assessed to determine alignment with thromboprophylaxis guidelines.A Quality Improvement (QI) phase from April 1, 2017 to December 31, 2017 added pharmacy oversight to perform an independent VTE risk assessment. Every patient started on an IMiD during this period underwent a separate VTE risk assessment by a pharmacist or hematologist. Each patient was categorized as high or low VTE risk based on NCCN guidelines. The results and recommendations for VTE prophylaxis were given to the myeloma provider.Results: In the initial retrospective review, 107 patients were identified who developed VTE during treatment of multiple myeloma with an IMiD despite thromboprophylaxis in 91 patients (85% of total; 78% on aspirin). The most common VTE risk factors per NCCN guidelines included cardiac disease (n=70), obesity (n=32), chronic kidney disease (n=27), and prior history of VTE (n=18). Eight patients received anticoagulant-based thromboprophylaxis.In the QI phase, 39 multiple myeloma patients were started on IMiDs. The risk assessment classified 17 as low-risk and 22 as high-risk. Of the high-risk patients, 14 (64%) were placed on an anticoagulant for thromboprophylaxis. Eleven (79%) of the anticoagulants used were direct oral anticoagulants (DOACs), 2 (14%) were a low-molecular weight heparin, one (7%) warfarin.The number of thromboembolic events that occurred were 6 (15%): 4 were high-risk on aspirin and 2 were low-risk on aspirin. The 2 low-risk patients who developed VTE had additional provoking factors (active infection, central line placement, smoking, a long driving trip).Eight high-risk patients were given aspirin. Out of the 8, 3 patients developed VTE and were then switched to anticoagulation. One high-risk patient received aspirin because of moderate thrombocytopenia and subsequently developed a VTE. No patients on anticoagulation developed a VTE. The number of complications attributed to thromboprophylaxis were 2 (5%). Two minor bleeding events occurred in patients who were on DOACs (1 epistaxis and 1 grade 1 GI bleed). Both patients continued DOAC anticoagulation after the event resolved.Conclusions: This two-phase QI study showed that multiple myeloma patients at high risk for VTE benefit from guideline-based thromboprophylaxis facilitated through a pharmacy-based system. DOAC's ease of use offer patients and providers an agreeable option that may improve compliance of VTE guidelines. However, prospective studies with DOACs in multiple myeloma are urgently needed to support this. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Peripherally Inserted Central Catheters (PICCs), the Leading Cause of Central Venous Catheter Associated Thrombosis in Children

IntroductionCentral venous catheters (CVC) are necessary for medically complex and acutely ill children, but come with the risk of venous thromboembolism (VTE) or central line associated blood stream infection (CLABSI). The rate of VTE in pediatrics has increased, most likely due to the increased use and placement of CVCs, and questions remain regarding VTE risk factors for CVC associated thrombosis.MethodsThis prospective, multi-center study compared the incidence and risk factors for VTE between peripherally inserted central catheters (PICCs) and centrally inserted tunneled lines (TLs) in patients 6 months to <18 years from 4 pediatric hospitals from September 2013 to April 2018. Data were collected through medical record review regarding demographics, medical history and specific CVC data including insertion technique and catheter specifications. Subjects were prospectively monitored via medical record review for CVC complications including VTE, CLABSI or malfunction (use of tissue plasminogen activator, malposition, blockage, etc).Cumulative incidence rates of VTE, CLABSI, CVC malfunction and removal were estimated and compared between PICCs and TLs. These analyses focused on the first 6 months from CVC insertion using parametric survival models assuming a Weibull survival distribution. The association between occurrence of VTE and subject/CVC characteristics was first assessed in univariate analyses, and then assessed by a minimal multivariable model.ResultsA total of 1,969 CVCs from 1,744 unique patients were included. Median age at CVC insertion was 6.4 years (range: 0.6-17.9) with the majority, 1048 (53%) placed in males. PICCs made up 1,259 (64%) of the CVCs and 710 (36%) were TLs.Among 1,969 CVCs, 100 had a VTE with a cumulative incidence rate of 5.4±0.5%, and median time to VTE from CVC insertion was 0.6 months (range 0-5.8 months). Eighty percent of the VTEs were in PICCs and median time to VTE was 0.5 months (range 0-5.3 months) in PICCs compared to TLs with a median time to VTE of 1.4 months (range 0-5.8 months). The incidence rate of VTE was 2.9±0.6% for TLs, and 6.8±0.7% for PICCs (Figure 1). In univariate analysis, subjects with TLs had a significantly lower risk of developing a VTE than patients with PICCs (HR=0.14, 95%CI: 0.05-0.4, p<0.001).The incidence of CLABSI was 14±1.3% for TLs compared to 7.9±0.9% for PICCs and in univariate analysis CVCs with a CLABSI were 4 times (95%CI: 1.3-13) as likely to develop a VTE. The cumulative incidence of malfunction in all CVCs was 25±1.0%, and univariate analysis revealed CVCs with a malfunction were 10 times (95%CI: 3.6, 28) as likely to develop a VTE.In the multivariable analyses (Table 1), subjects with TLs were significantly less likely to develop a VTE compared to PICCs (HR=0.16, 95%CI: 0.06-0.4, p<0.001); subjects with leukemia were more likely to have a VTE than subjects without cancer or other cancer diagnosis (HR=3.6, 95%CI: 1.3-9.9, p=0.050); subjects with a previous history of VTE were significantly more likely to develop a new VTE (HR=36, 95%CI: 6.3-210, p<0.001); and compared to CVCs with 1 lumen, CVCs with 2-3 lumens resulted in a higher risk of developing a VTE (HR=4.4, 95%CI: 1.9-10, p=0.002). Diagnosis of a CLABSI (HR=6.3, 95%CI: 2.1-18, p<0.001) as well as CVC malfunction (HR=5.7, 95%CI: 2.3-14, p<0.001) were also associated with higher risk of developing a VTE.ConclusionThis study represents the first prospective evaluation of the incidence and risk factors of VTE for TLs and PICCs placed in children. Almost 2,000 CVCs are included in this final analysis, which revealed a significant increase in VTE risk for children who have a PICC placed compared to a TL. The greatest risk factor for CVC associated VTE was a prior history of VTE. Additional risk factors included CLABSI, CVC malfunction, leukemia and having a multi-lumen CVC.Even though the ease of placing a PICC is enticing to avoid repeat peripheral intravenous (PIV) insertions or surgical intervention with TL placement, the increased risk of VTE in PICCs should give practitioners pause. When CVC placement is unavoidable, limiting the number of lumens is a modifiable VTE risk factor and efforts to prevent CLABSI may reduce VTE incidence. Interestingly, no insertion characteristics (e.g. placement vein, access side, catheter brand or material, tip location, insertion attempts) were associated with an increased risk of VTE. [Display omitted] DisclosuresJaffray:Octapharma: Consultancy; CSL Behring: Consultancy, Research Funding; Bayer: Consultancy. Young:Kedrion: Consultancy; Genentech/Roche: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; Bayer: Consultancy; Novo Nordisk: Consultancy, Honoraria; Shire: Consultancy, Honoraria.

Clinical Outcomes of Isolated Distal Deep Vein Thrombosis Associated with Cancer: The Cleveland Clinic Experience

Introduction:Although a randomized trial showed no difference in progression of VTE in patients with isolated distal deep vein thrombosis (IDDVT) treated with anticoagulation vs. serial ultrasound monitoring, cancer patients were excluded from this study and remain a high risk population. Furthermore, studies to evaluate the long-term clinical outcomes of IDDVT in cancer patients have been limited. Here we report patient outcomes from our experience in treating cancer-associated IDDVT.Methods:We evaluated a prospective cohort of patients referred to our centralized cancer-associated thrombosis (CAT) clinic at the Cleveland Clinic Taussig Cancer Institute from 8/2014-5/2018. We evaluated clinical characteristics, anticoagulation prescription, venous thromboembolism (VTE) recurrence rate, major bleeding, hospital admission, and overall survival in patients diagnosed with IDDVT compared to those with proximal events. Statistical methods included t-tests, chi-squared tests, Cox model and competing risks model where appropriate. Multivariable analysis was performed to identify risk factors associated with overall survival and recurrence rate.Results:Data from 1100 patients were included in the analysis. After excluding upper extremity DVT, a total of 302 (27.5%) VTE events were diagnosed, 122 (40.4%) of which were IDDVT. Of patients diagnosed with IDDVT, 14 (11.7%) had a history of prior VTE and 48 (55.8%) had documented stage 4 cancer (see table 1). Low molecular weight heparin (LMWH) was the most commonly prescribed anticoagulant (50.8%) followed by rivaroxaban (35.2%). Seven patients (5.7%) did not receive anticoagulation due to contraindication. Proximal events were seen more often in males vs. females (110/180 (61.1%) vs. 70/180 (38.9%), p=0.027 and in those with stage 4 disease vs. stage 0-3 (95/120 (79.2%) vs. 25/120 (20.8%), p=0.001. Rate of VTE recurrence (see figure 2) in patients initially diagnosed with IDDVT was similar to the rate of VTE recurrence in proximal DVT or pulmonary embolism (PE), with 1-year incident rate of 12.7% and 8%, respectively, (HR 1.31, 95% CI, 0.54 - 3.15, p= 0.55). There was no difference in rate of major bleeding 6 months after the initial event between patients with IDDVT and proximal events, 4/17 (23.5%) vs. 7/30 (23.3%), respectively, p=1.0. There was no difference in subsequent hospital admission between those with IDDVT and proximal events 48/122 (39.3%) vs. 73/175 (41.7%), respectively, p=0.77. After multivariable analysis, there was no difference in overall survival between IDDVT vs. proximal events HR 1.43 (95% CI 0.88-2.32), p=0.15 (see figure 1). Overall survival was negatively impacted in patients with stage 4 disease, hematologic malignancy, male gender, and symptomatic VTE.Discussion:This study demonstrates that cancer patients with IDDVT have a similar rate of VTE recurrence, subsequent hospital admission, rate of major bleeding, and overall survival compared to those with proximal events. These findings, if validated, suggest that treatment of cancer-associated IDDVT should mirror treatment of proximal events. DisclosuresKhorana:Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy.

Development of a Clinical Prediction Rule for the Risk of Venous Thromboembolism in Patients with Acute Leukemia

Background: The impact of venous thromboembolism (VTE) on morbidity and mortality is significant in hematological cancer patients, including acute leukemia (AL). However, VTE in AL receives little attention in comparison to other more frequently occurring complications. Identifying risk factors for the development of VTE among patients with AL will enable clinicians to stratify their patients according to their VTE risk and consider them accordingly for tailored surveillance or prophylaxis strategies.Methods: We aimed to derive a prediction rule for assessing VTE risk in AL patients. We conducted a retrospective cohort study of consecutive adult patients diagnosed with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) diagnosed between June 2006 and June 2017 at the London Health Sciences Centre, a tertiary care center in London, Ontario, Canada. Included participants were followed from diagnosis until last follow up, the occurrence of VTE, or death. Potential predictors were compared between groups using χ2 or Fisher's exact tests for categorical variables and T tests for continuous variables. Potentially significant predictors were evaluated using logistic regression and Cox regression analysis. A risk score was derived based on weighed variables included in the final model and compared using Kaplan-Meier survival analysis.Results: A total of 396 patients with AL (335 AML and 61 ALL) were included in the preliminary analysis. Population characteristics are shown in the Table. VTE occurred in 68 (17%) patients. Median time to VTE was 3 months (Interquartile range 1-5). In univariate analysis a diagnosis of ALL, prior history of VTE, platelet count at presentation and the number of attempts for line insertion were potential predictors. However, in multivariate analysis only ALL diagnosis and prior history of VTE remained significant. A score was derived based on these predictors (ALL 1 point; Prior VTE 2 points). Kaplan-Meier analysis showed good discrimination between categories (Figure; Log-rank p<0.001).Conclusion: We derived a score predictive of VTE in acute leukemia patients. Further confirmatory and validation studies are ongoing.Disclaimer. FA-A is a fellow of the CanVECTOR Network; ALL-L is an investigator of the CanVECTOR Network. This study was funded by the CanVECTOR Network which receives grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prospective Study of Apixaban for Primary Prevention of Venous Thromboembolism in Patients with Multiple Myeloma Receiving Immunomodulatory Therapy

IntroductionImmunomodulatory/cereblon-binding drugs (IMiDs), including lenalidomide and pomalidomide, have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic foundation at all phases of therapy. While these agents are generally well-tolerated, their increased risk of venous thromboembolism (VTE), in particular deep vein thrombosis and pulmonary embolism, presents a major clinical challenge for the treatment of MM. Apixaban, a direct oral anticoagulant which directly blocks Factor Xa, has been approved for treatment in patients with VTE. Apixaban has not been prospectively evaluated for thromboprophylaxis in MM in the US. In this phase IV single-arm study (NCT02958969), we prospectively evaluate the safety and efficacy of apixaban for primary prevention of VTE in patients with MM receiving IMiD therapy.MethodsFifty patients with MM on IMiD therapy received apixaban 2.5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for 6 months. Patients requiring therapeutic anticoagulation or with history of prior VTE were excluded. Patients stopped aspirin while on apixaban. Primary safety outcomes were rates of major hemorrhage and clinically relevant non-major hemorrhage over 6 months. Major bleeding was defined as overt bleeding associated with a decrease in hemoglobin of ≥ 2 g/dL, requiring transfusion of ≥ 2 units of blood, occurring in a critical site, or contributing to death. Clinically relevant non-major bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, surgical intervention, or interruption of the study drug. The primary efficacy outcome was the rate of symptomatic VTE over 6 months.ResultsBaseline characteristics are listed (Table). Median age was 63 years (range 51-74) with 50% of patients being male. Patients had received a median of 2 lines of therapy (range 0-8), and the majority (82%) had received prior autologous stem cell transplantation (AutoSCT). Patients received apixaban thromboprophylaxis in combination with lenalidomide (58%) or pomalidomide (42%). The majority (66%) received IMiDs for post-autoSCT consolidation or maintenance therapy. Most (80%) had traditional cardiovascular (CV) risk factors prior to initiation of apixaban, including hypertension (50%), obesity (46%), history of smoking (34%) and hyperlipidemia (32%).At planned interim analysis at 3 months (range 23-149 days) with data still being collected for planned 6 month study duration, no patients had experienced major hemorrhage or VTE. Two patients experienced clinically relevant, non-major hemorrhage, including one patient with unprovoked epistaxis lasting more than 5 minutes and another patient with mechanical trauma. These events were medically managed, and both patients were able to resume apixaban. One patient stopped therapy shortly after initiation due to allergic reaction to apixaban manifesting as generalized edema. No patients experienced stroke, myocardial infarction (MI), or death.ConclusionsIn this pilot study of 50 patients, low-dose apixaban was safe and well tolerated as thromboprophylaxis for patients with MM receiving IMiDs. No patients experienced VTE, major hemorrhage, stroke, or MI. Further randomized studies are needed to validate apixaban as a standard primary prevention anti-thrombotic strategy for patients with MM receiving IMiDs. [Display omitted] DisclosuresMoslehi:Bristol-Myers Squibb: Consultancy, Research Funding. Jagasia:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.