Use Of Prophylactic Anticoagulation Research Articles

Prior History of Venous Thromboembolism Is a Significant Risk Factor for Recurrence of Thrombosis after Cancer Diagnosis

Introduction: The risk of venous thromboembolism (VTE) is increased in patients with cancer and contributes to significant morbidity, treatment delays and mortality. The Khorana score is the most well-validated VTE risk prediction tool that guides use of prophylactic anticoagulation in patients with cancer. The Khorana score includes cancer type, body mass index (BMI), hemoglobin, platelet count and leukocyte count but not a prior history of VTE which may increase the risk of recurrent VTE. Scant published data have suggested that a personal history of VTE increases the risk of VTE recurrence by 2 to 7-fold after cancer diagnosis. In this study, we examine the impact of history of VTE on VTE recurrence in a large cohort of patients with cancer. Methods: We performed a retrospective cohort study of patients diagnosed with cancer using aggregated de-identified data from electronic medical record of >300 major hospitals in US (IBM Watson Explorys). Patients with a personal history of VTE (deep vein thrombosis and/ or pulmonary embolism) more than one year prior to the diagnosis of cancer were included. Within this cohort, patients who developed recurrent VTE within 180 days of diagnosis of cancer were identified. The primary end-point was the incidence of cancer associated VTE (CVTE) in patients with prior history of VTE as compared to patients without history of VTE. Baseline characteristics including age, race, gender, BMI, prothrombotic mutations (Factor V Leiden, prothrombin gene 20210A mutation), antineoplastic agent use, cancer type and laboratory values (as included in Khorana risk score) were compared in all patients. Results: A total of 4,159,400 patients with a diagnosis of cancer were included. Of these, 138,820 patients (3.3%) had a history of VTE >1 year prior to being diagnosed with cancer. The incidence of CVTE at 180 days was 10-fold higher in those with prior history of VTE compared to those without (36.9% vs 3.66%; OR 15.4, 95% CI 15.22-15.6, P value <0.0001). While the inherent risk of CVTE varied based on cancer type (highest risk of 10.5% in pancreatic cancer), the risk of recurrent VTE in patients with prior VTE history is magnified to a similar degree across all cancer types as shown in Figure 1. Baseline characteristics including age, race, gender and cancer type distribution were similar in all groups, as shown in Table 1. Factor V Leiden mutation or activated protein C resistance (FVL/APC) was more prevalent in patients with prior history of VTE and subsequent CVTE (3%) as compared to all patients with CVTE regardless of history (1%), as shown in Table 1. A higher BMI was noted in patients with prior history of VTE (49% and 71% respectively in patients with and without CVTE) as compared to 41% in all patients with CVTE. Greater use of antineoplastic agents (41%) was noted in the group of patients with prior history of VTE and subsequent CVTE as compared to patients with prior VTE but no CVTE (36%). Conclusion: Our study highlights that a prior personal history of VTE >1 year before cancer diagnosis significantly increases the risk of cancer associated VTE independently, regardless of other established risk factors for VTE suggesting that this group of patients, especially those undergoing anti-cancer treatment may benefit from prophylactic anticoagulation. Increased incidence of FVL/ APC in patients with prior history of VTE and recurrent CVTE may reflect increased testing for prothrombotic mutations in this cohort. Our ongoing efforts include examining the effect of addition of history of VTE to the Khorana score. Finally, large prospective observational studies would be key to assess the impact of history of VTE on cancer thrombosis. Disclosures No relevant conflicts of interest to declare.

Development and Baseline Characterization of a Thrombosis Risk Alert Tool: A Quality Assessment Project

Introduction: The Khorana Score (KS) is a validated tool to assess the risk of thrombosis in cancer patients, prior to initiation of chemotherapy. The AVERT and CASSINI studies evaluated prophylactic anticoagulation with apixaban or rivaroxaban for patients with KS of 2 or higher. Both studies demonstrated that while patients were taking prophylactic anticoagulant, the Hazard Ratio of cancer associated thrombosis was approximately 0.4. The NCCN and other societies are now recommending oral anticoagulant prophylaxis should be considered for up to 6 months, for patients with an intermediate or high-risk score of ≥2. Methods: We have developed a medical record tool, that identifies all MSKCC patients prior to initiation of a new chemotherapy regimen, captures the KS parameters, and generates the KS. Once fully implemented, it is anticipated that this tool and appropriate use of prophylactic anticoagulation, will reduce the burden of cancer associated thrombosis. To accurately document a potential reduction in rates of cancer associated thrombosis, we need to establish current baseline rates of cancer associated thrombosis via a contemporary verification of the KS, reflecting potential changes in oncology in the 12 years since the score was first published. We applied our KS capture tool to a 2-year period (10/17/2017 to 11/29/2019). 13,992 patients were identified with a new chemotherapy order, of whom 13,176 were found to have cancer and had complete parameters for the KS. We tracked all patients for 6 months, to identify possible episodes of Venous Thromboembolism (VTE). VTE episodes were identified by capturing the impressions of all contrast imaging studies, Doppler ultrasounds, and V/Q scans, combined with keyword and phrase computer identification, and manual review. To identify possible VTE events that occurred at an outside emergency department or hospital, we also queried new prescriptions for therapeutic doses of anticoagulants and ICD10 codes. In this analysis we focus on deep vein thrombosis (DVT) and pulmonary embolism (PE). Results: The 6-month rate of VTE (DVT or PE) was 6.4%. The VTE rate was 4.1% in the KS 0 cohort, and >18% for patients with a score of 4 or greater. We assessed the contribution of each parameter of the KS, in univariate analysis. Of the cancers assigned 2 points in the KS, pancreatic cancer had the highest VTE rate of 13.7%, but gastric/esophageal cancer did not have an increased rate. Of the cancers assigned 1 point, germ cell/testis, gynecologic, and lung cancer, also had increased risk of VTE, but bladder and non-Hodgkin lymphoma did not. Renal/urothelial cancers and cholangiocarcinoma/biliary tract cancers were also associated with high rates of VTE, although were not assigned points using the KS. Elevated BMI (≥35 kg/m2) was a weak risk factor. However, baseline anemia (<10 gm/dL), leukocytosis (>11,000/mcL) and thrombocytosis (≥350,000/mcL) were all strong predictors of VTE rate. Conclusions: The purpose of this QA project was to provide contemporary data on baseline cancer associated thrombosis rates, anticipating implementation of a program of targeted primary thrombosis prophylaxis. It remains clear that the KS provides a valuable risk assessment tool, stratifying 6-month VTE risk from 4.1% to >18%. Cancer type is typically the parameter that gets the first consideration. And most of the cancers with 1 or 2 points did predict increased risk. We don't have an explanation as to why, gastric/esophageal cancers and non-Hodgkin lymphoma were not associated with increased risk, but this finding may reflect the stage of their treatment at which patients begin care at MSKCC. Renal/urothelial, and cholangiocarcinoma/biliary tract cancers are associated with a high risk of VTE, and one may choose to include them for consideration of prophylactic anticoagulation. The relative contribution of pre-chemotherapy blood counts has been questioned in the past, but in this cohort, they clearly contributed to appropriate risk assessment. These data will serve as baseline for future assessment of thrombosis risk reduction upon implementation of a program of targeted prophylactic anticoagulation. Table Disclosures Khorana: Leap: Research Funding; BMS: Honoraria, Research Funding; Merck: Research Funding; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria. Mantha:MJH Associates: Honoraria; Physicians Education Resource: Honoraria. Soff:Amgen: Research Funding; Amgen: Honoraria; Janssen Scientific Affairs: Honoraria; Dova Pharmaceuticals: Honoraria; Bristol-Myers Squibb, Pfizer: Honoraria; Janssen Scientific Affairs: Research Funding; Dova Pharmaceuticals: Research Funding.

Venous Thromboembolism Prophylaxis Practices for Patients with Sickle Cell Disease Pre and during the COVID-19 Pandemic

Background: The coronavirus disease pandemic of 2019 (COVID-19) has been associated with coagulopathy and an increased rate of thrombosis in adults. Medical practitioners have been prompted to consider prophylactic anticoagulation in special populations diagnosed with COVID-19. Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state. Despite the concern for development of venous thromboembolism (VTE) in these patients, there are no standardized guidelines for routine thromboprophylaxis in either adults or children with SCD. Thus, VTE management options are often extrapolated from guidelines for the general population.Methods: A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through 7 SCD specific interest groups. Pediatric and adult practitioners were defined as those who medically manage patients 0-21 years of age and >21 years of age respectively. We examined responses to survey questions focused on routine thromboprophylaxis practices in children and adults with SCD prior to the pandemic and in patients with SCD admitted with COVID-19. Chi-square analyses or Fisher’s exact tests for small samples were used to compare proportions as needed.Results: The survey was distributed to approximately 2,550 providers. Of 93 total responses, 14% (N=13) only treat patients >21yo; 38.7% (N=36) only treat patients 0-21yo and 47.3% (N=44) treat both. Nearly all adult practitioners (96.6%) would recommend pharmacologic prophylaxis, mechanical prophylaxis or both for hospitalized adults, but only 76% of pediatric treaters would recommend any prophylaxis (PPX) in hospitalized children (p<0.0001, Figure 1). Only 16% would recommend pharmacologic PPX only for patients 0-21yo, with 36% preferring non-pharmacologic only methods and 24% preferring both forms. In contrast, for the >21yo patients, 51% preferred to use both pharmacologic and non-pharmacologic PPX, 25% preferred pharmacologic alone, with just 5.3% preferring non-pharmacologic PPX only. Enoxaparin was the most frequently used anticoagulant among both pediatric and adult practitioners [78% vs 89% respectively] (Figure 2). Direct oral anticoagulants (DOACS) were infrequently recommended (3.8% for SCD children and 10.9% for adults); of these, rivaroxaban was used most often. The most common indication for starting thromboprophylaxis for both 0-21yo and >21yo patients was history of prior VTE [81% and 81% respectively], followed by hip replacement [57% and 75% respectively].In patients admitted with COVID-19, prophylactic anticoagulation was recommended for adults by 94% of treaters. There was a significant increase in the use of prophylactic anticoagulation in children with COVID-19 vs. those without (84% vs. 40%; p=.0001). Figure 3 shows extended thromboprophylaxis practices upon discharge for COVID related admissions. Almost half of respondents (46%) would not recommend any thromboprophylaxis for children on discharge; 37% would recommend either 2-4 weeks or >4weeks of post-discharge PPX. The majority of adult providers would recommend discharge thromboprophylaxis for adults with 2 weeks post discharge (33%), and 2-4 weeks (30%) being the most common regimens.Conclusion:This pilot survey describes the thromboprophylaxis practices used for adult and pediatric SCD patients by specialty practitioners. In general, practitioners were likely to prescribe pharmacologic thromboprophylaxis for adults while mechanical PPX was preferred for children. However, in the high-risk setting of COVID-19 infection, pediatric practitioners would modify their practice to include pharmacologic thromboprophylaxis. Interestingly, despite the long-term availability of direct oral anticoagulants in adults, and recent completion of pediatric studies, the most commonly used pharmacologic agent pre-COVID in adults and children was enoxaparin. Of note, this survey was conducted prior to release of the International Society on Thrombosis and Haemostasis guidelines regarding discharge PPX in COVID-19. (Spyropoulos AC, J Thromb Haemost, 2020)These results highlight the influence of COVID-19 on the use of pharmacologic thromboprophylaxis, specifically in the pediatric population. Due to frequent hospitalization, studies are needed to guide decision making surrounding VTE PPX for the adult and pediatric inpatient SCD population.DisclosuresDavila:Spire Learning: Speakers Bureau; ATHN: Other: Grant Funding. Minniti:Bluebird bio: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; CLS Bering: Consultancy; Novartis: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Desai:Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Rockpointe Continuing Medical Education Company: Consultancy. O'Brien:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees.OffLabel Disclosure:Enoxaparin used as a form of thromboprophylaxis in children.

Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry

BackgroundSince April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. MethodsWe surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. ResultsAmong the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. ConclusionsThere is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies.

COVID-19 Pneumonia Hospitalizations Followed by Re-Presentation for Presumed Thrombotic Event

COVID-19 Pneumonia Hospitalizations Followed by Re-Presentation for Presumed Thrombotic Event

Head and Neck Microsurgeon Practice Patterns and Perceptions Regarding Venous Thromboembolism Prophylaxis.

Patients undergoing head and neck (H&N) microvascular reconstruction comprise a population at high risk for venous thromboembolism (VTE). Free flap and VTE thromboprophylaxis may coincide but tend to vary from surgeon to surgeon. This study identifies VTE prophylaxis patterns and perceptions among H&N microsurgeons in the United States. An online survey on VTE prophylaxis practice patterns and perceptions was emailed to 172 H&N microsurgeons in the United States using an anonymous link. There were 74 respondents (43% response rate). These surgeons completed residencies in otolaryngology (59%), plastic surgery (31%), and oral maxillofacial surgery (7%). Most underwent fellowship training (95%) and have practiced at an academic center (97%) for at least 6 years (58%), performing an average of 42 ± 31 H&N free flap cases per year (range = 1-190). Most adhered to general VTE prophylaxis guidelines (69%) while 11% did not and 20% were unsure. Nearly all surgeons (99%) would provide prophylactic anticoagulation, mostly in the form of subcutaneous heparin (51%) or enoxaparin (44%); 64% additionally used aspirin, while 4% used aspirin alone. The majority of surgeons (68%) reported having postoperative VTE complications, with six surgeons (8%) reporting patient deaths due to pulmonary embolism. A third of the surgeons have encountered VTE prophylaxis-related adverse bleeding events, but most still believe that chemoprophylaxis is important for VTE prevention (92%). While 35% of surgeons were satisfied with their current practice, most would find it helpful to have official prophylactic anticoagulation guidelines specific to H&N free flap cases. The majority of microsurgeons experienced postoperative VTE complications after H&N free flap reconstruction despite the routine use of prophylactic anticoagulation. Though bleeding events are a concern, most surgeons believe chemoprophylaxis is important for VTE prevention and would welcome official guidelines specific to this high-risk population.

Risk of venous thromboembolism, use of enoxaparin and clinical outcomes in obese patients undergoing laparoscopic adjustable gastric band surgery: A retrospective study.

There is a lack of clear guidance for the prophylactic use of anticoagulants for patients undergoing laparoscopic adjustable gastric banding (LAGB) surgery.This study aimed to evaluate the risk of venous thromboembolism (VTE), prophylactic use of enoxaparin and clinical outcomes in patients undergoing primary and revisional LAGB procedures.A retrospective study evaluated the prophylactic use of enoxaparin in adult patients who underwent primary and revisional (band and port) LAGB procedures. The incidence of VTE and major bleeding was investigated during a 90-day follow-up period. Descriptive and inferential statistics were used for data analysis.We included 112 and 100 patients who had undergone primary and revisional (24 band procedures and 76 port procedures) LAGB surgery, respectively. The majority of patients (97%) had a mild risk of VTE development using a post-discharge VTE risk calculator tool published from the Cleveland Clinic. All primary procedure patients received prophylactic enoxaparin, compared to 79% and 20% of revisional patients who underwent band and port procedures, respectively (P < .001). The overall VTE incidence was 0.9%, with no significant difference between patients who did or did not receive chemoprophylaxis (0.7% and 1.5%, respectively; P = .58). No major bleeding events were observed.Chemoprophylaxis may not be required in all patients undergoing low-risk LAGB surgery unless there are additional risk factors, such as the presence of super-super-morbid obesity or concomitant hormone replacement therapy. More studies are needed on the prophylactic use and dosing of enoxaparin in patients undergoing LAGB procedures to provide high-level evidence.

Prophylactic Anticoagulation While Hospitalized for Premature Prelabor Rupture of Membranes: A Decision Analysis [31L

INTRODUCTION: Premature prelabor rupture of membranes (PPROM) necessitates hospital admission thus limiting activity and theoretically increasing the risk for venous thromboembolism (VTE). While prophylactic anticoagulation decreases the risk of VTE, it may increase the risk for postpartum hemorrhage (PPH) and affect the ability to obtain neuraxial analgesia. This study analyzed the use of prophylactic anticoagulation during hospitalization for PPROM with a decision analysis model. METHODS: The designed decision-analytic model compared the use of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or no anticoagulation in women with a singleton pregnancy admitted to the hospital for PPROM after 24 weeks who remained hospitalized until delivery. Assumptions included: induction of labor at 34 weeks or earlier spontaneous labor; therapeutic use of LMWH in the setting of new onset VTE; and universal desire for neuraxial analgesia. The outcomes of VTE, PPH, spontaneous labor, route of delivery, and type of anesthesia attained were assessed. One and two way sensitivity analyses were performed to interrogate model assumptions and a Monte Carlo probabilistic sensitivity analysis was performed using uniform distributions. RESULTS: No prophylactic anticoagulation is the chosen strategy based on the highest expected value and sensitivity analyses. No prophylaxis was the preferred choice 78% of the time, UFH 20% of the time, and LMWH 2% of the time. CONCLUSION: Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for PPROM. These findings can be used to inform clinical decisions when admitting low risk singleton pregnancies with PPROM.

Novel Coronavirus Infection: A Review on Haematological Markers of Disease Severity

The Corornavirus Disease (COVID-19) virus infection has a wide range of presentation- asymptomatic, mild, severe and critical forms that often lead to death from respiratory failure. There is a strong relationship between the severity of COVID-19 infection and some haematological parameters. Patients often present with lymphocytopenia at diagnosis despite having a normal total white cell count. The degree of lymphocytopenia could predict the progression to pneumonia and subsequent need for ventilator support due to respiratory failure. Apart from lymphocytopenia, thrombocytopenia has been linked with increased severity of COVID-19 symptoms. The lymphocyte-platelet ratio has been found to a better marker for disease severity than isolated lymphocytopenia or thrombocytopenia. COVID-19 patients have been found to be at increased risk of Venous Thromboembolism (VTE). There is elevation of D-dimers, abnormalities of the Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) among hospitalised COVID-19 patients. This has necessitated the use of prophylactic anticoagulation even in the early phases of the infection.

Implementation of a Prophylactic Anticoagulation Guideline for Patients with Traumatic Brain Injury

Patients with traumatic brain injury (TBI) are at an increased risk of developing complications from venous thromboembolisms (VTEs [blood clots]). Benchmarking by the American College of Surgeons Trauma Quality Improvement Program identified suboptimal use of prophylactic anticoagulation in patients with TBI. We hypothesized that institutional implementation of an anticoagulation protocol would improve clinical outcomes in such patients. A new prophylactic anticoagulation protocol that incorporated education, weekly audits, and real-time adherence feedback was implemented in July 2015. The trauma registry identified patients with TBI before (PRE) and after (POST) implementation. Multivariable regression analysis with risk adjustment was used to compare use of prophylactic anticoagulation, VTE events, and mortality. A total of 681 patients with TBI (368 PRE, 313 POST) were identified. After implementation of the VTE protocol, more patients received anticoagulation (PRE: 39.4%, POST: 80.5%, p < 0.001), time to initiation was shorter (PRE: 140 hours, POST: 59 hours, p < 0.001), and there were fewer VTE events (PRE: 19 [5.2%], POST: 7 [2.2%], p = 0.047). Multivariable analysis showed that POST patients were more likely to receive anticoagulation (odds ratio [OR] = 10.8, 95% confidence interval [CI] = 6.9-16.7, p < 0.001) and less likely to develop VTE (OR = 0.33, 95% CI = 0.1-1.0, p = 0.05). Benchmarking can assist institutions to identity potential clinically relevant areas for quality improvement in real time. Combining education and multifaceted protocol implementation can help organizations to better focus limited quality resources and counteract barriers that have hindered adoption of best practices.

Factors associated with pregnancy outcomes in women with a history of cerebral sinus venous thrombosis.

To collect and summarize pregnancy outcomes among women with a history of cerebral sinus vein thrombosis (CSVT). A retrospective multicenter case-control study. The study group comprised all women diagnosed with CSVT during 2004-2018 at four university hospitals, and with follow-up data of pregnancy. A control group of women with a singleton pregnancy was established by matching, four-to-one, according to maternal age. The data of 74 pregnancies of 65 women with CSVT were analyzed. The median time-to-pregnancy interval from the CSVT was 4.2 [2.7-6.8] years. Anticoagulation therapy in the form of enoxaparin was administered in 68 (91.9%) pregnancies. Adjunctive low-dose aspirin was used throughout 12 (16.2%) pregnancies. Overall, 54 (73.0%) of the pregnancies ended in live births and 20 (27.0%) in miscarriage. The use of anticoagulation therapy during pregnancy was positively associated with live birth outcome (P < 0.001). Late adverse outcomes were encountered in 19 (25.7%) pregnancies, including the delivery of a small for gestational age infant (n = 12), gestational hypertensive disorders (n = 6) and placental abruption (n = 3). The use of adjunctive aspirin was associated with a lower rate of late adverse pregnancy outcomes (P = 0.03). No recurrent CSVT, thrombosis at other sites, and major bleeding episodes were observed during pregnancy. Live-birth rate was higher (P = 0.007) and the rate of late adverse outcome was lower (P = 0.01) for the control (n = 296) than the study group. Among pregnant women with a prior CSVT, no recurrent thrombosis events were observed during gestation. The use of prophylactic anticoagulation was associated with live birth. The use of adjunctive aspirin should be further studied in this setting, as its utilization correlated with a lower rate of late pregnancy complications.

Timing of Prophylactic Anticoagulation and Its Effect on Thromboembolic Events After Surgery for Metastatic Tumors of the Spine.

Retrospective cohort study. To investigate the effect of timing of initiation of prophylactic anticoagulation (AC) on the incidence of venous thromboembolism (VTE) after surgery for metastatic tumors of the spine. VTE is a known complication in patients undergoing surgery for metastatic spine disease. However, there is limited data on the use of prophylactic AC in this population and its impact on the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the risk of epidural hematoma. A retrospective review of our institutional neurosurgical spine database for the years 2012 through 2018 was performed. Patients who underwent surgery for metastatic tumors were identified. The development of VTE within 30 days was examined, as well as the occurrence of epidural hematoma. The incidence of VTE was compared between patients receiving "early" (within postoperative days 1-3) and "delayed" prophylactic AC (on or after postoperative day 4). Sixty-five consecutive patients were identified (mean age 57, 62% male). The overall rate of VTE was 16.9%-all of whom had DVTs with a 3.1% rate of nonfatal PE (two patients also developed PE). From the overall cohort, 36 of 65 (56%) received prophylactic AC in addition to mechanical prophylaxis-22 in the early group (61.1%) and 14 in the delayed group (38.9%). The risk of VTE was 9.1% in the early group and 35.7% in the delayed group (26.6% absolute risk reduction; P = 0.049); there was one case of epidural hematoma (1.5%). On multivariate analysis, delayed prophylactic AC was found to significantly increase the odds of VTE development (OR 6.43; 95% CI, 1.01-41.2; P = 0.049). The findings of this study suggest that administration of prophylactic AC between days 1 and 3 after surgery for metastatic tumors of the spine may significantly reduce the risk of postoperative thromboembolic events. 4.

Venous Thromboembolism in Neurocritical Care Patients.

Venous thromboembolism (VTE) is a potentially life-threatening complication among critically ill patients. Neurocritical care patients are presumed to be at high risk for VTE; however, data regarding risk factors in this population are limited. We designed this study to evaluate the frequency, risk factors, and clinical impact of VTE in neurocritical care patients. We obtained data from the electronic medical record of all adult patients admitted to neurological intensive care unit (NICU) at Henry Ford Hospital between January 2015 and March 2018. Venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both diagnosed by Doppler, chest computed tomography (CT) angiography or ventilation-perfusion scan >24 hours after admission. Patients with ICU length of stay <24 hours or who received therapeutic anticoagulants or were diagnosed with VTE within 24 hours of admission were excluded. Among 2188 consecutive NICU patients, 63 (2.9%) developed VTE. Prophylactic anticoagulant use was similar in patients with and without VTE (95% vs 92%; P = .482). Venous thromboembolism was associated with higher mortality (24% vs 13%, P = .019), and longer ICU (12 [interquartile range, IQR 5-23] vs 3 [IQR 2-8] days, P < .001) and hospital (22 [IQR 15-36] vs 8 [IQR 5-15] days, P < .001) length of stay. In a multivariable analysis, potentially modifiable predictors of VTE included central venous catheterization (odds ratio [OR] 3.01; 95% confidence interval [CI], 1.69-5.38; P < .001) and longer duration of immobilization (Braden activity score <3, OR 1.07 per day; 95% CI, 1.05-1.09; P < .001). Nonmodifiable predictors included higher International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) scores (which accounts for age >60, prior VTE, cancer and thrombophilia; OR 1.66; 95% CI, 1.40-1.97; P < .001) and body mass index (OR 1.05; 95% CI, 1.01-1.08; P = .007). Despite chemoprophylaxis, VTE still occurred in 2.9% of neurocritical care patients. Longer duration of immobilization and central venous catheterization are potentially modifiable risk factors for VTE in critically ill neurological patients.

Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications

BackgroundAn increased incidence of thromboembolic events (TE) are reported in nephrotic syndrome (NS) leading to recommendations for prophylactic anticoagulation (PAC). However, as no randomized clinical trial has established the efficacy or risks associated with PAC, guidelines are empiric or substantiated only by estimates of risks and benefits.This study evaluates the risk of TE and hemorrhagic complications in patients with NS treated with PAC and compares to patients not receiving PAC.MethodsWe included patients diagnosed with NS from two Danish nephrology departments with different practices for the use of PAC. Patients were included if presenting with NS from September 2006 to January 2012, a P-albumin < 30 g/L, and renal biopsy confirming non-diabetic, glomerular disease. Patients aged < 16 years, on renal replacement therapy, or administered anticoagulants at the onset of NS were excluded. Bleeding episodes and/or TE were identified from patient records. Bleeding episodes were divided into minor and major bleeding.ResultsOf the 79 patients included, 44 patients received PAC either as low or high dose low-molecular-weight heparin (LMWH) or as warfarin with or without LMWH as bridging, while 35 did not receive PAC. P-albumin was significant lower in the PAC group compared to those not receiving PAC. Significantly more TEs was observed in the non-PAC group compared to the PAC group (4 versus 0 episodes, P = 0.035). The TEs observed included one patient with pulmonary embolism (PE), one with PE and deep vein thrombosis, one with PE and renal vein thrombosis, and one with a stroke. Five patients with bleeding episodes were identified among those receiving PAC, of which two were major and three were minor, while two patients in the non-PAC group experienced a minor bleeding episode (P = 0.45 between groups). The major bleeding episodes only occurred in patients receiving PAC in combination with low dose aspirin.ConclusionsIn patients with NS the use of PAC was associated with a decreased risk of clinically significant TE, but may also be associated with more bleeding episodes although not statistically significant. Only patients treated with PAC in combination with anti-platelet therapy had major bleeding episodes.

SUN-LB025 Superior Mesenteric Artery Thrombosis: An Uncommon Complication of Diabetic Ketoacidosis

Introduction: Diabetic Ketoacidosis (DKA) has been shown to promote a prothrombotic state. Mortality rate in DKA can be as high as 20% due to thromboembolic complications. Acute mesenteric ischemia has mortality rates of 60-80% due to late and difficult diagnosis. Very few cases of superior mesenteric artery (SMA) thrombosis associated with DKA have been described in literature. The presentation of acute SMA thrombosis can be masked by concurrent DKA due to its non-specific signs and symptoms and laboratory markers leading to delay in diagnosis and treatment. Case: A 68-year-old female with Type 2 diabetes since 25 years was hospitalized with nausea, vomiting and abdominal pain of 3 days duration. Initial lab work showed: Serum glucose 631 mg/dl (n 70-140 mg/dl), bicarbonate 11 mmol/L (n 22-28 mmol/L), anion gap 32(n 12-16), lactic acid 3.0 mmol/L (n 0.5-2.2 mmol/L), HbA1c 14.1 % (n 4.6-6.5%) and serum osmolarity of 310 mOsm/kg (n 275-295 mOsm/kg). CECT abdomen on admission was unremarkable. She was adequately managed for DKA with intravenous fluids and insulin. Lactic acid normalized with fluids and anion-gap closed within 24 hours of admission. However, she kept complaining of diffuse abdominal pain described as sharp and deep inside the abdomen. D-dimer and repeat lactic acid were elevated at 1,155 ng/ml (n 150-234 ng/ml) and 2.4 mmol/L (n 0.5-2.2 mmol/L) respectively. CT angiography obtained at 48 hours from the time of admission showed occlusion of SMA at its mid-portion, approximately 7 cm distally from origin with abrupt loss of contrast signal at branch point of the ileocolic artery after several jejunal branches. She underwent urgent SMA thrombectomy, exploratory laparotomy and small bowel resection. Echocardiogram didn’t reveal any cardiac source of embolism or septal defects. EKG showed sinus rhythm and patient didn't have any prior history of thromboembolism or cardiac arrhythmias. Laboratory panel for thrombophilia and screening for auto-immune disorders was negative. Patient recovered well post surgery and was started on anti-coagulation. Discussion: We didn't find any other risk factor for arterial thrombosis in our case other than diabetic ketoacidosis and uncontrolled diabetes. Studies have shown that Free Protein S and Protein C activity levels decrease and von Willebrand factor levels increase during DKA. Platelet hyperreactivity, coagulation activation, hyperosmolarity, endothelial damage and impaired fibrinolysis- all contribute to hypercoagulability during DKA. Routine use of prophylactic anticoagulation in DKA is controversial. Clinicians should maintain a high index of suspicion of thrombosis in DKA. Pain out of proportion to the physical exam findings and persistent abdominal pain and lactic acidosis despite treatment should point towards mesenteric ischemia. Early diagnosis and treatment of mesenteric ischemia in critical in influencing the survival. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

A lung cancer patient with deep vein thrombosis:a case report and literature review

BackgroundVenous thromboembolism (VTE) is a common problem in cancer patients and the incidence is increasing, especially for patients with lung cancer. Common features of these patients, like advanced stage, male gender, old age and chemotherapy, are risk factors of VTE. Here we reported a case in which the patient with lung cancer developed deep vein thrombosis (DVT) when receiving chemotherapy.Case presentationA 53-year-old male who was diagnosed with lung cancer with multiple metastasis developed severe DVT during chemotherapy. Despite the use of aspirin, warfarin and low molecular weight heparin (LMWH) for anticoagulant and thrombolytic therapy, the condition was still deteriorating, resulting in amputation finally.ConclusionsIt’s rare that the conditions of cancer patients who develop venous thromboembolism (VTE) keep deteriorating despite the administration of aspirin, warfarin and low weight molecular heparin. Both early diagnosis and prophylactic use of anticoagulants are suggested for cancer patients to improve the prognosis.

Multi-occupational collaboration in appropriative use of prophylactic anticoagulants for venous thromboembolism in trauma patients

Multi-occupational collaboration in appropriative use of prophylactic anticoagulants for venous thromboembolism in trauma patients

Associations of anticoagulant use with outcome in newly diagnosed glioblastoma

BackgroundTo test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. MethodsWe assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. ResultsAnticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18–1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. ConclusionsAnticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma.

The use of prophylactic anticoagulation during induction and consolidation chemotherapy in adults with acute lymphoblastic leukemia.

Treatment for acute lymphoblastic leukemia (ALL) in adults confers a high risk of venous thromboembolic (VTE) complications. We describe the implementation and results of prophylactic anticoagulation guidelines in adults (18-50years) treated on a Dana-Farber Cancer Institute ALL pediatric inspired consortium protocol from 2007 to 2013. A high rate of asparaginase related toxicity events, including thrombosis, resulted in a protocol amendment adding guidelines for prophylactic anticoagulation and a modified asparaginase dose and schedule. After excluding patients with Philadelphia positive ALL, a cohort of 36 patients were treated after the protocol amendment with prophylactic anticoagulation and compared to 49 patients who received no prophylactic anticoagulation. Bleeding complications were not significantly different in those treated with prophylactic anticoagulation compared with those enrolled prior to the amendment (p = 0.26). No patients on prophylactic anticoagulation had grade ≥ 3 bleeding. Prior to the amendment, the 2year cumulative incidence of VTE post-induction was 41% compared to 28% while on prophylactic anticoagulation (p = 0.32). The 2year cumulative incidence pulmonary embolus pre-amendment was 16% compared with 8% post-amendment (p = 0.34). Prophylactic anticoagulation can be safely administered to adults with ALL without increasing the number or severity of bleeding events and, in addition to modifications in the asparaginase regimen, resulted in a reduction in the cumulative incidence of VTE.

Risk of thromboembolism in cisplatin versus carboplatin-treated patients with lung cancer.

IntroductionCarboplatin is widely used to treat lung cancer in the United States as an alternative to cisplatin. Several studies have demonstrated that cisplatin-based regimen is associated with a high frequency of thromboembolic complications. However, there has been limited investigation directly comparing the risk of thromboembolic events (TEEs) between cisplatin- and carboplatin-treated patients with lung cancer.MethodsAll lung cancer patients treated with cisplatin or carboplatin at Wilmot Cancer Center, University of Rochester between 2011 and 2014 were included. Patient characteristics including exposure (cisplatin vs. carboplatin) and outcome (TEEs between the time of the first dose of cisplatin or carboplatin and 4 weeks after the last dose) were collected by reviewing electronic medical records. A Fisher’s exact test was used to compare the proportion of incident TEEs between cisplatin and carboplatin groups. The risk of TEE associated with carboplatin compared to cisplatin was assessed using multiple logistic regression.ResultsAmong 415 subjects, 317 patients (76.4%) received carboplatin and 98 (23.6%) patients received cisplatin. In the carboplatin group, 10.9% (33/302) of evaluable patients developed treatment-related TEEs vs. 14.7% (14/95) in the cisplatin group. There was no significant difference in the risk of developing TEEs between the two groups (P = 0.32). However, 15.2% of carboplatin-related TEEs were arterial thromboses compared to none in the cisplatin group.ConclusionsThe incidence of carboplatin-related TEEs was high in lung cancer patients without significant difference in the risk of developing TEEs between cisplatin and carboplatin groups. Potential use of prophylactic anticoagulation in all platinum-treated patients should be further investigated.