Deep Venous Thrombosis Pulmonary Embolism Research Articles

Arthroplasty at Very High Altitude with Restricted Resources: Our Experience and Review of Literature.

Patients living in high altitudes are often deprived of total knee arthroplasty (TKA) due to logistic reasons, economic, and social challenges in performing surgical procedures for management of knee pain. Surgical procedures in high-altitude dwellers have associated risk of deep venous thrombosis/pulmonary embolism (DVT/PE). In patients undergoing these procedures at lower altitudes, return to high altitudes can cause high-altitude pulmonary edema (HAPE). We share our experience of performing TKA in high-altitude dwellers by setting up a surgical camp at 11,000 feet. A retrospective assessment of patients undergoing total knee arthroplasty at a camp set up at 11,000 feet between 2014 and 2020 was undertaken. Follow-up data of patients which included clinical assessment by the Knee Society Score (KSS) and complications like DVT, infection, residual deformity, etc. were included in the study. Radiographic evaluation to look for evidence of implant loosening was also inculcated. 132 patients (202 knee joints in 50 male and 82 female patients) underwent TKA during annual camps. The average follow-up of patients was 60months. Mean pre-operative KSS was 38, which was increased to 83 at 1-year follow-up post-surgery. There was no evidence of DVT or superficial or deep infection in any patient in the post-operative period. With this study, we want to highlight that total knee arthroplasty can be safely performed at high altitudes and remote areas with limited health facilities. We believe it is a safer and more convenient prospect for the residents of high-altitude regions. III.

Shear wave elastography values of thrombus in patients with lower extremity deep vein thrombosis for pulmonary embolism detection: the ROC analysis

Rationale: Thrombosis of the iliac (IV) and femoral veins (FV) is one of the most common causes of pulmonary embolism (PE). Modern ultrasound scanners are equipped with the technology of shear wave elastography, which gives a quantitative assessment of thrombus stiffness by Young's modulus reconstruction. However, the lack of convincing data on the role of thrombus stiffness for clinical manifestations of PE hinders the active use of shear wave elastography to diagnose the risk of embolism.
 Aim: To determine the threshold values of the venous thrombus Young’s modulus for deep venous thrombosis (DVT) of the lower extremities complicated by massive PE and/or PE with acute cor pulmonale (ACP).
 Materials and methods: This was a single center cross-sectional study in 101 patients who were hospitalized with the diagnosis of acute (duration of less than 2 weeks) or subacute (from 2 weeks to 3 months) IV and FV thrombosis. Doppler ultrasound of the lower extremity veins and echocardiography were done in all patients. Forty eight patients with clinical signs of PE had chest computed tomography. The venous thrombus stiffness was assessed by shear wave elastography with the Young's modulus reconstruction. We performed the ROC analysis for mean values of the Young's modulus for proximal segments of IV and FV thrombi in patients with DVT and massive PE and ACP.
 Results: PE was diagnosed in 40.6% (26/64) of the patients hospitalized with acute DVT and in 54.1% (20/37) of those with subacute DVT. Echocardiographic signs of ACP in massive PE were found in 47.4% (9/19) of the patients, in submassive and minor PE in 55.6% (15/27). In DVT complicated with PE, the ROC analysis of the shear wave elastography results gave the following threshold values of the mean Young’s modulus for the proximal thrombus segment: for acute IV thrombosis + PE and ACP, ≤ 16.7 kPa (AUC 0.714, sensitivity 100%, specificity 42.1%), in subacute IV thrombosis + PE and APC, ≤ 23.7 kPa (0.939, 100 and 90.9%, respectively), in acute FV thrombosis + massive PE, ≥ 9.5 kPa (0.706, 100 and 50%, respectively), in subacute FV thrombosis + massive PE, ≥ 24.4 kPa (0.550, 60.0 and 68.8%, respectively).
 Conclusion: Shear wave elastography of deep vein thrombi of the lower extremities makes it possible to identify patients with PE and ACP during acute and subacute IV thrombosis and to determine massive PE in acute FV thrombosis.

330 Accuracy and Clinical Significance of Neurosurgical Patient Safety Indicator Events Reported by Centers for Medicare Services

INTRODUCTION: Data on patient safety indicator (PSI) events are used by Center for Medicare Services (CMS) for determining reimbursement to hospitals, and public quality reporting. It is unclear whether the process used by CMS to detect PSI events is accurate, and whether PSI events affect clinical outcomes in neurosurgical patients. METHODS: We reviewed CMS reported PSI events in neurosurgical patients at our hospital from July 1, 2018, through December 31, 2019. Discharge billing codes were reviewed in order to assess whether CMS criteria for PSI were met. Charts were reviewed by experienced clinicians in order to assess the accuracy and clinical significance of CMS reported PSI events. For deep venous thrombosis/pulmonary embolism (DVT/PE) PSI events, chart reviews were performed in order to assess whether standard of care prophylaxis was administered. RESULTS: 14 PSI events were reported in 11 patients, representing 1.3% of neurosurgical procedures in fee for service medicare patients. 7 patients underwent spinal surgery and 4 underwent cranial surgery. PSI events included DVT/PE (n = 6), postoperative hematoma (n = 2), postoperative respiratory failure (n = 5), and iatrogenic pneumothorax (n = 1). Only 10/14 PSI events (71%) met CMS criteria based on discharge billing codes, and only 8/14 PSI events (57%) met CMS criteria based on chart review. All PSI events that were confirmed based on chart review required specific medical or surgical treatment, but only 5 (63%) led to increased length of stay, and no patients had residual adverse effects at hospital discharge. 5/6 patients with chart confirmed DVT/PE (83%) received standard of care DVT prophylaxis. CONCLUSIONS: CMS-reported PSI events have significant rates of inaccuracy. PSI events may not correlate with meaningful adverse clinical outcomes. DVT/PE PSI events were not associated with breaches in standard of care.

The efficacy and safety of low-molecular-weight heparin in patients undergoing knee arthroscopic surgery and anterior cruciate ligament reconstruction

PurposeTo inveatigate how effective LMWH was at preventing venous thromboembolism (VTE), major bleeding events, and minor bleeding events after simple knee arthroscopic surgery and anterior cruciate ligament reconstruction (ACLR). MethodsWe conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, and the CNKI database for potentially eligible articles. The outcomes were evaluated in terms of odds ratio (OR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata software and subgroup analyses were performed based on the surgical setting including ACLR and simple knee arthroscopic surgery. ResultsA total of eight studies with 2249 patients and 1794 controls were included in this meta-analysis. In patients undergoing simple knee arthroscopic surgery, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic deep venous thrombosis (DVT), symptomatic pulmonary embolism (PE), symptomatic VTE, and did not increase the risk of major bleeding events, but did have a higher risk of minor bleeding events (OR = 1.95, 95% CI 1.34–2.84, P = 0.000) and a lower risk of asymptomatic DVT (OR = 0.14, 95% CI 0.04–0.53, P = 0.004) in comparison with non-LMWH prophylaxis. In patients undergoing ACLR, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic DVT, symptomatic PE, symptomatic VTE, and did not increase the risk of major bleeding events and minor bleeding events, but did have a lower risk of asymptomatic DVT (OR = 0.43, 95% CI 0.23–0.78, P = 0.006). ConclusionWhen compared to a control group, this meta-analysis found that LMWH had little potential benefit in preventing major VTE (symptomatic VTE, symptomatic DVT, and symptomatic PE) after simple knee arthroscopy and ACLR. As a result, LMWH should not be considered routinely in patients undergoing knee arthroscopic surgery.

C-9 | Outcomes of Extracorporeal Membrane Oxygenation in COVID-19: Updated Meta-Analysis

Due to recent nature of the COVID-19 pandemic, the goals and guidelines for extracorporeal membrane oxygenation (ECMO) in COVID-19 are similar to non-COVID-19 patients and mostly small observational studies have been conducted. Our aim is to analyze the mortality and other outcomes of ECMO in COVID-19 patients using the data available to date. We collected 2239 articles from Cochrane, Embase, and PubMed. Among these, 51 retrospective and observational studies describing outcomes in COVID-19 patients treated with ECMO were included. The primary outcome was mortality, and secondary outcomes were ECMO complications. Random effects model was used for pooled proportions with logit transformation with a 95% confidence interval (CI), and Higgins I-squared statistics were used to evaluate heterogeneity. In 51 studies including 13400 COVID-19 patients on ECMO, pooled proportion for mortality was 0.41 (95% CI 0.36-0.46, I2 89%, p<0.01) (Fig 1). While pooled proportions were 0.4 (95% CI 0.26-0.57, I2 94%, p<0.01) for bleeding, 0.12 (95% CI 0.09-0.15, I2 76%, p<0.01) for stroke, 0.25 (95% CI 0.19-0.33, I2 89%, p<0.01) for pulmonary embolism/deep venous thrombosis (PE/DVT) and 0.34 (95% CI 0.26-0.43, I2 92%, p<0.01) for renal replacement therapy (RRT) (Fig 2). Mortality of COVID-19 patients on ECMO is higher than overall mortality of COVID-19 patients as patient requiring ECMO tend to be sicker with higher co-morbidity burden and poor outcomes. ECMO complications of bleeding, stroke, PE/DVT and RRT were observed in COVID-19 patients on ECMO but due to hypercoagulable state of COVID-19, the rates of the complications are increased.

175 Patient Safety Indicator 04 Does not Consistently Identify Failure to Rescue in the Neurosurgical Population

INTRODUCTION: Patient safety indicator (PSI) 04 is a quality index designed by the Agency for Health Research and Quality to measure Failure to Rescue (FTR). PSI 04 has been scrutinized for inaccurately measuring FTR, a framework developed to capture a hospital’s ability to identify and manage preventable complications and post-operative mortality. METHODS: We conducted a single-center retrospective cohort study. We identified patients from 1/12/2017-6/1/2021 who sustained a PSI 04-attributed complication (pneumonia, deep venous thrombosis/pulmonary embolism (DVT/PE), sepsis, shock/cardiac arrest, or gastrointestinal (GI) hemorrhage/acute ulcer), underwent a neurosurgical procedure, and had inpatient mortality. The primary outcome was whether the attributed PSI 04 designation was the primary driver of mortality. RESULTS: We identified 67 patients who met PSI 04 criteria (median age, 61; female sex, 43.4%). Nearly 20% of patients met the PSI complication criteria prior to admission. Patients who underwent emergent bedside procedures were more likely to present with poor GCS (P = 0.016), more likely to be intubated prior to admission (P = 0.016), and less likely to have mortality due to a PSI 04-related complication (P = 0.002). PSI 04-related complications were identified as the cause of death in only 43.2% of cases. Procedures occurring in the interventional radiology suite (OR, 23.2; 95% CI, 3.5-229.3; P = 0.003) or the operating room (OR, 6.2; 95% CI, 1.25-39.5; P = 0.03) were more likely to have mortality due to a PSI 04-related complication compared to bedside procedures. CONCLUSIONS: Most neurosurgical procedures meeting PSI 04 criteria took place outside of a traditional operating room and may capture a fundamentally different patient population. 65.7% of patients were inappropriately flagged as meeting PSI 04 criteria. PSI 04 currently identifies patients with complications unrelated to operating room procedures. Improvement in patient safety within neurosurgery necessitates the development of a subspecialty specific measure to capture FTR.

Feasibility, effectiveness, and safety of edoxaban administration through percutaneous endoscopic gastrostomy: 12-months follow up of the ORIGAMI study.

Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. ORIGAMI was a prospective, single-arm, observational study (NCT04271293). Patients with PEG and an indication for long-term anticoagulation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. The primary endpoint was the composite of cardio-embolic events consisting of ischemic stroke, systemic embolism, or symptomatic deep venous thrombosis/pulmonary embolism (DVT/PE). Secondary endpoints were the number of bleeding events and edoxaban plasma concentrations at steady state. We here report the 12-month results. A total of 12 patients were enrolled. The main indication for PEG implantation was amyotrophic lateral sclerosis (10/12). The primary endpoint of cardio-embolic events did not occur in any patients at 12 months. All patients were in the therapeutic range of steady-state edoxaban plasma levels. Three minor bleedings were observed, while no major bleedings occurred during the observational period. A total of five patients died. All deaths were from non-cardiovascular causes and were consistent with the natural history of the pre-existing severe disease. Our study suggests that edoxaban administration via PEG is feasible and appears safe and effective in fragile, comorbid patients, resulting in therapeutic plasma concentrations of edoxaban. [ClinicalTrials.gov], identifier [NCT04271293].

Appropriateness of Prescribing Rivaroxaban at King Khalid University Hospital Riyadh.

Background and aimWarfarin is recognized as a first-line treatment for different coagulopathy conditions; however, guidelines also encourage the use of rivaroxaban as an alternative option. The recent approval of the novel oral anticoagulants (NOACs) has led to swift changes in anticoagulant prescribing practices. This study aimed to review rivaroxaban prescribing patterns in adult patients in a large tertiary care setting in the Kingdom of Saudi Arabia (KSA).Materials and methodsA retrospective cross-sectional study was conducted from January 2019 to September 2020 at King Khalid University Hospital, Riyadh, KSA. Data was collected from the patient's medical record. Data analysis was performed with the Statistical Package for the Social Sciences (SPSS) IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.ResultsA total of 309 patients were included in this study. Rivaroxaban use for non-valvular atrial fibrillation (NVAF) was relatively higher than deep venous thrombosis/pulmonary embolism (DVT/PE). 45% of the patients had NVAF, followed by DVT/PE (26%), and DVT/PE prophylaxis (25%). Fifty-six patients, (18%) received an inappropriate dose of rivaroxaban for NVAF.ConclusionThis study found a relatively high percentage of inappropriate rivaroxaban prescribing, predominantly because of inappropriate dosing, which can potentially increase medication-related events. The use of rivaroxaban should be monitored to increase the appropriateness of therapy and improve patient safety.

ASAIO 2021 Annual Meeting Abstracts.

Study: Deep venous thrombosis (DVT) is said to be the most preventable cause of death in hospitals today (Centers for Disease Control, February 2020). This silent killer most frequently starts in the lower extremities as a small thrombus that initially forms in a valve pocket located behind a venous valve leaflet. Failure to initiate preventative measures to reduce the risk of DVT can result in the development of life-threatening pulmonary emboli (PE) and chronic venous insufficiency (CVI). These risks are currently exacerbated by the current SARS-CoV-2 pandemic that has increased the frequency of DVT formation and PE in patients through mechanisms that are not fully understood. The current study is using artificial intelligence (AI) and machine learning (ML) to evaluate changes in blood rheology, venous blood flow, and venous valve configuration that can lead to increased risk of DVT, PE, and CVI. Methods: In our model, AI/ML is used to evaluate previously recorded images of normal and abnormal cadaver veins and venous valves. Using these data, we can predict that previous DVT formation produced the observed leaflet damage and will increase the risk of CVI and future DVT formation. The contribution that changes in blood rheology could make to venous blood flow abnormality will also be assessed. We leverage the latest advances in image processing to quantify the valve leaflet geometry with respect to the susceptibility to recurrent DVT. Results: Based on this data, AI/ML will predict, on a patient-by-patient basis, the probability of deep venous thrombosis formation. This will allow healthcare professionals to determine when preventative measures are most appropriate. It will also allow physicians to assess whether a patient has an increased risk of developing a future DVT and/or CVI insufficiency. With this information patient care can be improved and the debilitating and life-threatening complications of DVT can be substantially reduced.

Supplementing the Subinternship: Effect of E-Learning Modules on Subintern Knowledge and Confidence

Supplementing the Subinternship: Effect of E-Learning Modules on Subintern Knowledge and Confidence

Risk Assessment and Outcome of Venous Thromboembolism in Pediatric Population in an Academic Care Center of a Low-Middle Income Country.

Venous thromboembolism (VTE) is a recognized complication of hospital stay in young patients in many developed countries, but such an information is largely unavailable from a low middle-income country (LMIC). This study aimed at identifying the frequency, risk factors, treatment options and outcome of deep venous thrombosis/pulmonary embolism (DVT/PE) in pediatric population in a tertiary care center from a LMIC. International classification of disease, ninth revision (ICD-9) was used to identify VTE in patients aged 0-18 years during January 2011 to September 2019. In-house computerized system was used to collect data for demographics, clinical and laboratory details. SPSS version 19 was used to analyzed data. The study was approved by Institutional ethical review committee (3872-Pat-ERC-15). During the study period, 134617 pediatric patients were hospitalized, DVT/PE was observed in 77 unique patients (47 males and 30 females) with a median (IQR) age of 14 (5-16) years equivalent to 5.9 VTE events /10,000 hospital admissions. Malignancy, community acquired infections and autoimmune diseases were the predominant risk factors (75%) in adolescent age-group while surgery for congenital heart anomalies was the primary reason (71%) in infants. Overall, lower extremity thrombosis was the most frequent (51%) followed by pulmonary embolism (25%). and upper extremity thrombosis (24%). Enoxaparin and unfractionated heparin were mainly used to treat VTE and all-cause mortality was 13% in the cohort studied. We observed substantial VTE events in pediatric patients during their hospital stay in a tertiary care center of a low-middle income country.

1776P - High incidence of venous thromboembolic events (VTE) in patients with diffuse large b-cell lymphoma

BackgroundIncidence of venous thromboembolic events (VTE) is higher among cancer patients, especially while on chemotherapy. Diffuse large B-cell lymphoma (DLBL) is the most common lymphoma. Studies that specifically evaluated the risk of VTE in patients with different kinds of lymphomas reported a risk ranged from 1.5% to 14.6%. In this study, we specifically address VTE in a unified lymphoma population. MethodsMedical records and hospital databases were searched for patients with a diagnosis of DLBL and VTE. All patients were diagnosed, treated and followed up at our institution. The Khorana and “Throly” risk assessment models (RAM) were applied on all patients and known risk factors for VTE were studied. ResultsA total of 393 patients (52.4% males), median age: 49 (range: 18-90) years were included. At diagnosis, 163 (41.5%) were stage IV, 116 (29.5%) had bulky disease and 197 (50.1%) had high LDH. All patients were treated on a unified guidelines using R-CHOP chemotherapy; 285 (72.5%) achieved CR while 72 (18.3) had salvage chemotherapy. Venous thromboembolic events were reported in 57 (14.5%) patients. Pulmonary embolism (PE) with or without deep venous thrombosis (DVT) was reported in 24 (42.1%), 8 of them (33.3%) were incidental. Upper extremity DVT were seen in 18 (31.6%); only 4 (22.2%) were associated with a vascular device. Thrombosis was diagnosed in ambulatory sitting in 30 (52.6%) and majority of the VTE occurred while on active chemotherapy; 20 (35.1%) while on initial induction and 15 (26.3%) while on salvage chemotherapy, however, 19 (33.3%) occurred before the initiation of any chemotherapy. Among the 35 patients on active chemotherapy, only 6 (17.1%) had high Khorana risk score. In a multivariate analysis, significantly higher rates of thrombosis were associated with stage-IV disease, high LDH and high International Prognostic Index (IPI). Sex, age, BMI, and the Khorana risk score were not. ConclusionsIncidence of VTE in patients with DLBL is high and majority of such events occurred in ambulatory setting were VTE prophylaxis is not offered. Upper extremity DVT and incidental PE were exceptionally high. Stage at diagnosis, IPI score and LDH are important in predicting the risk for thrombosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Assessment of Non-vitamin K Oral Anticoagulants Use in a Tertiary Care Center in the USA: A Chart Review of 909 Patients.

Non-vitamin K oral anticoagulants (NOACs) have emerged as an attractive alternative to vitamin K antagonists for various thromboembolic indications. However, prescribed NOAC doses are often inconsistent with drug labeling and prescribers might not consider the potential risks associated with concomitant use of other drugs, which can compromise NOACs' safety and effectiveness. A retrospective chart review was conducted in a tertiary care center in USA over a 4-month period. We studied patients whose home medications included NOACs and assessed the appropriateness as per drug labeling, taking into consideration relevant clinical factors and concomitant drug intake. A total of 909 patients with a mean age of 70.6 ± 13.1years, out of which 51.6% were males, were included. The majority of patients received NOACs for stroke prevention in atrial fibrillation (AF) (70.5%), or deep venous thrombosis/pulmonary embolism (DVT/PE) treatment (13.5%). The most common drug prescribed was apixaban (57.8%) followed by rivaroxaban (34.0%), and less frequently dabigatran (7.7%). Inappropriate dosing was significantly more frequent among older patients, those taking NOACs for AF, those taking a higher number of home medications, and those with a lower creatinine clearance. Seven hundred and six patients (77.67%) had at least one drug-NOAC interaction, out of which 515 were rated major interactions. Antiplatelets, amiodarone, non-steroidal anti-inflammatory medications, and calcium channel blockers were the most commonly interacting drugs. A significant number of patients received NOACs at doses inconsistent with the package labeling or had clinically significant drug-drug interactions with NOACs. Efforts are warranted to improve appropriate dosing and avoid significant drug interactions.

Risk of pulmonary embolism and deep venous thrombosis in patients with asthma: a nationwide case-control study from Sweden.

Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma.We conducted this nationwide case-control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sex- and education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders.Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37-1.50), for DVT of 1.56 (95% CI 1.47-1.65) and for combined PE and DVT of 1.60 (95% CI 1.32-1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT.Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE.

Evaluation of Rivaroxaban and Dalteparin in Cancer Associated Thrombosis

Introduction: Venous thromboembolism (VTE) in the form of deep venous thrombosis (DVT) or pulmonary embolism (PE) is a complication of malignancy. Several studies have demonstrated the superiority of dalteparin (Fragmin®), a low molecular weight heparin (LMWH), in comparison to oral vitamin K antagonists in preventing VTE recurrence in the setting of active cancer. LMWH is the preferred treatment of cancer associated thrombosis. However, the cost of LMWH can be prohibitive and the need for daily subcutaneous injections can decrease patients' quality of life. While rivaroxaban (Xarelto®), a Factor Xa inhibitor, has been approved for the treatment and secondary prevention of DVT and PE, there is limited data regarding its use in cancer patients. The objective of our study is to determine the efficacy and safety of rivaroxaban compared to dalteparin in cancer associated thrombosis.Methods: This is a retrospective chart review of cancer patients greater than age 18 treated at H. Lee Moffitt Cancer Center between May 3, 2010 and June 30, 2015 on anticoagulation with rivaroxaban or dalteparin. Patients were excluded if the length of anticoagulant therapy was < 30 days, anticoagulant therapy was initiated > 6 months after VTE diagnosis, the indication for treatment was not DVT/PE, if patients had contraindications to either LMWH or rivaroxaban, or patients were not on treatment doses of therapy. Out of 459 patients identified, 226 patients (107 in the rivaroxaban group, and 119 in the dalteparin group) were eligible for analysis based on our exclusion criteria. Efficacy was determined by the incidence of recurrent VTE, such as recurrent DVT, new fatal or non-fatal PE within 30 days. The secondary endpoint of the study was to determine the safety of rivaroxaban compared to dalteparin in cancer patients for the treatment of VTE. Safety was determined by the incidence and severity of bleeding. Major bleeding was defined as clinically overt if it was associated with a fall in hemoglobin of 2 g/dL or more, required transfusions of ≥ 2 units of packed red blood cells, involved retroperitoneal, intracranial, or critical site bleeding, or if it contributed to death. Minor bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of anticoagulation treatment, or associated with any other discomfort such as pain or impairment of activities of daily life. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. All data was analyzed using SPSS version 21.0 statistical software.Results: Rivaroxaban had a similar rate of DVT and PE failure with 1 event versus 2 with dalteparin (p = 0.625). The rivaroxaban group had 0 major and 8 minor bleeds compared to 3 major and 8 minor bleeds in the dalteparin group with p values of 0.09 and 0.86 respectively. Comorbidities and risk factors for thrombosis were similar in both groups as summarized in Table 1.TableRivaroxaban vs. Dalteparin: No Significant Differences in the Efficacy and Safety Profile in Cancer Associated ThrombosisRivaroxabanN = 107DalteparinN =119P valueDVT Failure within 30 days1 (0.93%)2 (1.68%)0.625PE Failure within 30 days1 (0.93%)1 (0.84%)0.94Major Bleeding0 (0 %)3 (2.5%)0.09Minor Bleeding8 (7.5%)8 (6.7%)0.864Median Age (Yrs)61650.93MaleFemale58 (54.2%) 49 (45.8%)60 (50.4%) 59 (49.6%)0.596Active Cancer96 (86.5%)111 (93.2%)0.350Surgery within 30 Days14 (13.1%)13 (10.9%)0.684Hypertension58 (54.2%)61 (51.3%)0.69Diabetes14 (13.1%)14 (11.8%)0.84Coronary Artery Disease6 (5.61%)11 (9.2%)0.326History of Previous DVT12 (11.2%)5 (4.2%)0.074BMI >3039 (36.4%)48 (40.3%)0.585Creatinine Clearance (Cr Cl) 30 - 50 Cr Cl 50 - 707 (6.5%) 100 (93.3%)7 (5.9%) 112 (94.1%)0.837Conclusions: Our study evaluated the safety and efficacy of rivaroxaban compared to dalteparin in patients with predominantly active cancer treated at a large comprehensive cancer center and found rivaroxaban to be comparable to dalteparin in this cohort. There were no significant differences in regards to recurrent VTE or major/minor bleeding with patients on rivaroxaban or dalteparin in our cohort of patients. Large randomized trials evaluating the efficacy and safety of rivaroxaban in the oncology population are needed to further validate our findings. DisclosuresNo relevant conflicts of interest to declare.

Testosterone therapy, thrombophilia, and hospitalization for deep venous thrombosis–pulmonary embolus, an exploratory, hypothesis-generating study

Our hypothesis was that testosterone therapy (TT) interacts with previously undiagnosed thrombophilia–hypofibrinolysis, leading to hospitalization for deep venous thrombosis (DVT)–pulmonary emboli (PE). We determined the prevalence of DVT–PE associated with TT 147 men hospitalized in the last 12months for DVT–PE. Of the 147 men, 2 (1.4%) had TT before and at the time of their DVT–PE. Neither had risk factors for thrombosis. Neither smoked. Case #1 (intramuscular T 50mg/week) had 2 PE, 6 and 24months after starting TT. DVT–PE in case #2 (T gel 100mg/day) occurred 24months after starting T. Both men were found to have previously undiagnosed familial thrombophilia (protein S deficiency, homocysteinemia, high Factor VIII). In case #2, on 100mg T gel/day, serum estradiol was high, 51pg/ml (upper normal limit 42.6pg/ml). At least 1.4% of men hospitalized for DVT–PE were on TT and had previously undiagnosed thrombophilia, suggesting a thrombotic interaction between exogenous T and thrombophilia–hypofibrinolysis. Given the increasing use of TT, our preliminary findings should facilitate design of a much-needed, multi-center, prospective study of pro-thrombotic interactions between T therapy and thrombophilia for subsequent thrombotic events including DVT–PE.

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Introduction: Subdural hematoma (SDH) affects >100,000 patients/year in the US and leaves >50% of its victims dead or severely disabled. Coagulopathy is an independent predictor for death and disability after SDH. Optimal treatment for coagulopathy-associated SDH remains controversial. Prothrombin complex concentrate (PCC) may rapidly reverse coagulopathy in warfarin-associated SDH (wSDH) but may increase thromboembolic (TE) complications. We hypothesize that PCC use in wSDH may decrease time to surgery from rapid coagulopathy reversal and therefore decrease mortality, but may increase in-hospital TE complications Methods: From a single center prospective database we identified 82 consecutive acute wSDH patients from 2008–2012 with admission INR>1.4. All patients were treated per standardized protocol for rapid warfarin reversal with conventional therapy (FFP+IV vitamin K). Additional 3-factor PCC may be used at treating physician’s discretion. Patients with “do-not-resuscitate” orders within 24 hours of admission, multiple anticoagulant use, chronic SDH, SDH associated with multisystem trauma, and with GCS of 3 and fixed and dilated pupils on presentation were excluded. Primary endpoint was in-hospital and 6-months mortality. Secondary endpoints were time to surgery and incidence of deep venous thrombosis/pulmonary embolism (DVT/PE) and troponin elevation. Propensity scores adjustment was used to reduce confounding. PS for PCC use were modeled using age, gender, mean arterial pressure, admission INR, presence of fixed dilated pupils, GCS, presence of multiple SDH, SDH diameter, SDH location, and midline shift as covariates. Conditional logistic regression models matched on quartiles of propensity score were used to compare in-hospital and 6-month all-cause mortality between PCC-treated and conventional therapy groups. Results: PCC-treated (n=38) and conventional therapy groups (n=44) had similar mean age, gender, baseline hypercoagulable conditions, and median initial INR on presentation. PCC-treated group had lower median GCS on presentation compared with conventional therapy group (14 vs. 15, p<0.0001). PCC-treated group received fewer units of FFP transfusion compared with conventional therapy (median 4 vs. 6 units, p=0.003). Overall in -hospital (OR: 1.61 [0.19–13.62], p=0.66) and 6-month mortality (OR: 3.24 [0.85–12.41], p=0.09) were not different between PCC-treated and conventional therapy group after PS adjustment. PCC use was independently associated with reduced time to surgery (-1.92 [(-2.70)–(-1.20)] after PS adjustment. Univariate analysis showed PCC group had higher incidence of DVT/PE (16% vs. 0%, p=0.006) and troponin elevation (32% vs. 14%, p=0.04) compared to conventional therapy. However, after PS adjustment there were no between-group differences in the incidence of DVT/PE or troponin elevation. Conclusions: Warfarin reversal with PCC reduced time to surgery and decreased the number of FFP transfusion needed but did not reduce in-hospital or 6-month mortality in wSDH. PCC use was not independently associated with increased TE complications in wSDH. Future prospective randomized studies are necessary to determine the risk versus benefit of PCC use in wSDH, and to determine whether rapid correction of coagulopathy leads to better neurological outcome and decreased mortality in wSDH.

Testosterone Therapy, Thrombophilia–Hypofibrinolysis, and Hospitalization for Deep Venous Thrombosis-Pulmonary Embolus

In our study of 596 men hospitalized in the last 3 years for deep venous thrombosis-pulmonary emboli (DVT-PE), we determined the prevalence of exogenous testosterone (T) use with subsequent development of DVT-PE. Of the 596 men, 110 were now dead, 97 had cancer thought to cause DVT-PE, 250 could not be contacted, leaving 139, of whom 7 had taken T before and at the time of their admissions, 1.2% of the total cohort, a conservative estimate of the prevalence of T-associated DVT-PE. In all, 5 of the 7 DVT-PE events occurred within 3 months of initiation of T, with mean and median intervals between initiation of T and hospitalization with DVT-PE 6.7 and 2 months. Of the 7 men treated with exogenous T, all 5 men who had evaluation of thrombophilia-hypofibrinolysis were found to have previously undiagnosed familial or acquired thrombophilia or hypofibrinolysis, suggesting a thrombotic interaction between exogenous T and thrombophilia-hypofibrinolysis.

Low-dose recombinant factor VIIa for trauma patients with coagulopathy

Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothetising that it would be effective and safe. We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation. Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0 s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome. Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.

An study on screening the gene clusters associated with pulmonary embolism-deep venous thrombosis by oligo microarray

To find out the gene clusters associated with pulmonary embolism-deep venous thrombosis (PE-DVT) and elucidate the molecular genetic mechanism of PE. Peripheral venous blood samples were collected from 9 PE patients and 33 normal controls. The total RNA was extracted and purified. Nine PE cRNA probes labeled with cyanine 3 were constructed, and one standard cRNA probe labeled with cyanine 5 was synthesized based on the total RNA mixture of the controls. Hybridization with Agilent Whole Human Genome Oligo Microarray was performed. Eleven of the genes screened were randomly selected to be amplified by fluorescence quantitative PCR (FQ-PCR). 434 differential expression genes were screened from the 9 microarrays, including 36 gene transcripts. Associated with blood coagulation, 20 with immune or inflammatory response, 29 with metabolism, 26 with cell differentiation and apoptosis, 25 with cell growth/maintenance, 22 with cell-cell signaling or signal transduction, 14 with cytoskeleton or motility, 15 with ion channel or ion transport, 14 with transcription, and 6 with DNA/RNA binding. These 11 of these genes were randomly selected to be amplified by FQ-PCR. The differential expression of the 11 selected genes was consistent with the microarray. The differential expression of a lot of genes in the body may play a role in the process of initiation and development of PE-DVT.