BACKGROUND:Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors.METHODS:100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics / patient knowledge and attitudes regarding SCDs / and patient self-reported bother with SCDs.RESULTS:Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1-3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance.CONCLUSIONS:Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety.

Background As a major cause of morbidity and mortality treatment of venous thromboembolism is important, with the correct use of anticoagulants it is possible to greatly reduce both mortality and morbidity. Warfarin is among the most widely used anticoagulants being effective in treatment and prevention of venous thromboembolism with few negative side effects other than bleeding complications. With a narrow therapeutic window warfarin treatment requires constant monitoring and adjustments to stay effective without an increased bleeding risk. The aim of this thesis was to study the efficacy and safety of warfarin treatment in venous thromboembolic disease. Methods Using AuriculA, the Swedish national quality register for atrial fibrillation and anticoagulation, a cohort was created of patients registered with warfarin treatment during the study time January 1st 2006 to December 31th 2011, including all different indications for anticoagulation. In all four studies the study design was retrospective with information added to the cohort from the Swedish national patient register about background data and endpoints in form of bleeding complications in all studies and thromboembolic events in study 1 and 2. In study 3 and 4 information was added from the cause of death register about occurrence of death and in study 3 cause of death. In study 3, information from the prescribed drugs register about retrieved prescriptions of acetylsalicylic acid was added. Results In study 1 the mean TTR was found to be high both among patients managed at primary healthcare centres and specialised anticoagulation clinics at 79.6% and 75.7%. There was no significant difference in rate of bleeding between the two types of managing centres being 2.22 and 2.26 per 100 treatment years. In study 2 no reduction in complication rate with increasing centre TTR was seen for patients with atrial fibrillation with few centres having centre TTR below 70% (2.9%), in contrast to previous findings by Wan et al(1). For those with warfarin due to VTE where a larger proportion of the centres had centre TTR below 70% (9.1%) there was a reduction in complication rate with increasing centre TTR. Among the 13859 patients with treatment for VTE in study 3 age (HR 1.02, CI 95% 1.01-1.03), hypertension (HR 1.29, CI 95%1.02-1.64), Cardiac failure (HR 1.55, CI 95% 1.13-2.11), chronic obstructive pulmonary disease (HR 1.43, CI 95% 1.04- 1.96), alcohol abuse (HR 3.35, CI 95% 1.97-5.71), anaemia (HR 1.77, CI 95% 1.29-2.44) and a history of major bleeding (HR 1.75, CI 95% 1.27-2.42) increased the risk of bleeding during warfarin treatment. In study 4 both those with high iTTR and those with low INR variability had a low rate of bleedings at 1.27 (1.14-1.41) or 1.20 (0.94-1.21) per 100 treatment years compared to those with low iTTR and high INR variability having a rate of bleeding at 2.91 (2.61-3.21) or 2.61 (2.36-2.86) respectively. Those with the combination of both low iTTR and high INR variability had an increased risk of bleeding, hazard ratio HR 3.47 (CI 95 % 2.89-4.17). The quartile with both the lowest iTTR and the highest INR variability had an increased risk of bleeding with a hazard ratio 4.03 (3.20-5.08) and 3.80 (CI 95%, 3.01-4.79) compared to the quartile with the highest iTTR and lowest INR variability. Conclusion It is possible to achieve a safe warfarin treatment both in specialised anticoagulation centres and in primary health care. At initiation of treatment some of the patients at high risk of bleeding can be identified using knowledge about their background. With the use of quality indicators as TTR and INR variability during treatment those at high risk of complications can be identified and analysing treatment quality on centre level gives an opportunity to identify improvement areas among managing centres. With the addition of new treatment options warfarin can still be the most suitable option for some patients, being safe and effective when well managed.

Background: Pulmonary embolism (PE) accounts for almost 40% of perioperative deaths after bariatric surgery. Placement of prophylactic inferior vena cava (IVC) filter before bariatric surgery to improve outcomes has shown varied results. We performed a meta-analysis to evaluate postoperative outcomes associated with the preoperative placement of IVC filters in these patients. Methods: A systematic review was conducted by three investigators independently in PubMed, EMBASE, the Web of Science and Scopus until February 28, 2013. Our search was restricted to studies in adult patients undergoing bariatric surgery with and without IVC filters. Primary outcomes were postoperative deep vein thrombosis (DVT), pulmonary embolism (PE), and postoperative mortality. Meta-analysis used random effects models to account for heterogeneity, and Sidik-Jonkman method to account for scarcity of outcomes and studies. Associations are shown as Relative Risks (RR) and 95% Confidence Intervals (CI). Results: Seven observational studies were identified (n=102,767), with weighted average incidences of DVT (0.9%), PE (1.6%), and mortality (1.0%) for a follow-up ranging from 3 weeks to 3 months. Use of IVC filters was associated with an approximately 3-fold higher risk of DVT and death that was nominally significant for the former outcome, but not the latter (RR 2.81, 95%CI 1.33-5.97, p=0.007; and RR 3.27, 95% CI 0.78-13.64, p=0.1, respectively); there was no difference in the risk of PE (RR 1.02, 95%CI 0.31-3.77, p=0.9). Moderate to high heterogeneity of effects was noted across studies. Conclusions: Placement of IVC filter before bariatric surgery is associated with higher risk of postoperative DVT and mortality. A similar risk of PE in patients with and without IVC filter placement cannot exclude a benefit, given the potential large imbalance in risk at baseline. Randomized trials are needed before IVC placement can be recommended. / Revisión por pares

Diana.sobieraj@hhchealth.org / Objective To systematically review the literature and to quantitatively evaluate the efficacy and safety of extended pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA). Methods A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, through September 2014) and searching of reference lists of included studies and relevant reviews was conducted to identify randomized controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding). A random-effects Frequentist approach to NMA was used to calculate relative risks with 95% confidence intervals. Results Ten trials (n=11,079) were included. Risk of bias (assessed with the Cochrane tool) was low in most domains assessed across the included trials. Apixaban (2.5mg and 5mg), dabigatran, rivaroxaban, idraparinux and vitamin K antagonists (VKA) each significantly reduced the risk of VTE recurrence compared to placebo, ranging from a 73% reduction with idraparinux to 86% with VKAs. With exception of idraparinux, all active therapies significantly reduced VTE recurrence risk versus aspirin, ranging from a 73% reduction with either apixaban 2.5mg or rivaroxaban to 80% with VKAs. Apixaban and aspirin were the only therapies that did not increase composite bleeding risk significantly compared to placebo. All active therapies except aspirin increased risk of composite bleeding by 2 to 4-fold compared to apixaban 2.5mg, with no difference found between the two apixaban doses. Conclusion Extended treatment of VTE is a reasonable approach to provide continued protection from VTE recurrence although bleeding risk is variable across therapeutic options. Our results indicate that apixaban, dabigatran, rivaroxaban, idraparinux and VKAs all reduced VTE recurrence when compared to placebo. Apixaban appears to have a more favorable safety profile compared to other therapies. / Revisión por pares

Malignancy is associated with a hypercoagulable state manifested clinically by an increased incidence of venous thromboembolism (VTE). Colorectal cancer (CRC) patients who develop VTE have reduced survival. This increased mortality extends beyond the acute VTE event, suggesting that VTE is associated with aggressive tumour biology. Tissue factor (TF) and other clotting factors have been implicated in this process. However, the significance of clotting factors in the tumour microenvironment (TME) remains unknown. The aim of this thesis is to i) determine if a procoagulant TME is a biomarker for poor prognosis and VTE in patients undergoing resectional surgery for CRC and ii) determine the effect of TF, thrombin and FXa on proliferation and migration in vitro in CRC and if their inhibitors have potential as anticancer therapies. In the in vitro studies, epithelial expression of TF had a modest effect on proliferation and migration when quantified using the PrestoBlue proliferation and transwell migration assays. Exogenous TF, FXa and thrombin all increased migration in DLD-1 wild type cells. In addition, exogenous thrombin increased proliferation amongst SW620 wild type cells. This suggests that coagulation factors from the TME, rather than epithelial expression, may influence tumour biology. Moreover, dabigatran, a direct thrombin inhibitor, abrogated the pro-proliferative effects of thrombin, which highlights its potential role as an anticancer therapy. In a multicentre, prospective cohort study of 159 CRC patients undergoing resectional surgery, rates of duplex screen detected deep vein thrombosis (DVT) were correlated to plasma and tumour markers of hypercoagulability. TF is upregulated in the stroma of cancer compared to normal tissue. However, stromal TF expression decreased in more advanced (T4) tumours. This suggests that a procoagulant TME has a role in early tumourigenesis. In total, 5.4%, 7.0% and 9.1% of patients had an asymptomatic DVT pre- operatively, at six weeks post-surgery and after the commencement of adjuvant chemotherapy respectively. The development of a post-operative complication was a risk factor for DVT, whilst locally advanced tumours resulted in a prolonged hypercoagulable state i.e. raised D-dimer at six weeks. This highlights a possible role for pre- and post- operative screening duplex ultrasonography and super-extended VTE prophylaxis in selected patients. In conclusion, this thesis establishes a role for exogenous coagulation factors in promoting tumour biology in CRC. VTE is more common amongst patients undergoing resectional surgery for CRC than previously estimated. The utility of tumour and plasma hypercoagulabilty as biomarkers for survival in CRC will be further analysed when long term follow-up data is available.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

Intro/Aims: Venous thromboembolism (VTE) is a common complication in cancer patients. The role of thrombophilic polymorphisms in cancer related VTE remains poorly explored. Aim 1 of this study was to determine if Factor V Leiden (G1691A), Prothrombin (PT) G20210A or methylenetetrahydrofolate reductase (MTHFR) C677T are associated with the increased occurrence of VTE in adult oncology subjects compared to nononcology subjects. Aim 2 of this study was to determine if cancer patients with the MTHFR C677T polymorphism who are treated with antimetabolite therapy have an increased incidence of VTE compared to cancer patients who are treated with other chemotherapy.Setting/Methods: A descriptive, comparative, retrospective chart analysis was utilized for this study in an outpatient hematology, oncology clinic in Southern Arizona. Enrolled were 100 adult subjects (age 18 - 85) with documented history of VTE (27 subjects with cancer and 73 noncancer). Subjects were evaluated for Factor V Leiden, PT G20210A, and MTHFR C677T prior to the study. Eleven subjects were treated with antimetabolite chemotherapy and 8 subjects were treated with other chemotherapy.Results: The overall polymorphism frequency for Factor V Leiden was 21%, PT G20210A 4%, and MTHFR C677T 50%. Factor V Leiden was found in 11.1% of cancer subjects and 24.7% of noncancer subjects. Prothrombin G20210A was found in 3.7% of cancer subjects and 4.1% of noncancer subjects. MTHFR C677T was present in 25.9% of cancer subjects and 58.9% of noncancer subjects. No statistical significance was observed between subjects treated with an antimetabolite and positive for MTHFR C677T compared with those treated with other types of chemotherapy.Conclusion: Analysis of the data collected in this study demonstrated overall higher rates than the expected frequencies of all polymorphism for both the cancer and noncancer patients with documented VTE. In this small retrospective study, the only significant finding was that the MTHFR C677T polymorphism was more prevalent in the noncancer group.Currently, there are no specific guidelines for VTE prevention in the outpatient oncology setting. Identification of risk factors, including prothrombotic mutations may reduce risk of VTE and provide guidance for prophylactic treatment recommendations in the outpatient setting.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post-discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post-order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.