Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common and preventable cause of morbidity among individuals and hospital in-patient mortality. Further, it imposes a substantial burden upon the community and its health care system and economy. Studies performed in Western societies suggest that the annual incidence of DVT is about 0.8 to 1.2 per 1,000, PE about 0.3 to 0.6 per 1,000, and VTE about 1.0 to 1.8 per 1,000. However, it is not known if these estimates can be generalised to the Australian population because of differences in ethnic composition and other risk factors for VTE among the different populations. In this thesis, I undertook a prospective, community-based cohort study over a 13-month period in 2003 – 2004 to determine the incidence and crude event rate of symptomatic, objectively verified VTE in north-east metropolitan Perth. The study population was broadly representative of the national Australian population in terms of age, sex and ethnic distribution. Cases were identified through multiple overlapping sources. The incidence of DVT, PE and VTE in the community were 0.52 (95% confidence interval, CI: 0.41 – 0.63), 0.31 (95% CI: 0.22 – 0.40) and 0.83 (95% CI: 0.69 – 0.97) per 1000 per year, respectively. The annual incidence of DVT, adjusted to the World Standard population, was 0.35 (95% CI: 0.26 – 0.44) per 1000, PE 0.21 (95% CI: 0.14 – 0.28) per 1000 and VTE 0.57 (95% CI: 0.47 – 0.67) per 1000. The crude event rate for VTE was 0.85 (95% CI: 0.71 – 0.99) per 1000 per year. These findings suggest that the incidence of DVT, PE and VTE are lower than in other Western societies studied. Possible reasons include a lower prevalence of exposure to causal risk factors (genetic and environmental) and incomplete case ascertainment. Knowledge of the local incidence and event rate allows health planners to allocate appropriate resources and evaluate cost-effective preventive measures.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (leaves 64-74).

INTRODUÇÃO: A literatura demonstra que tromboembolismo venoso permanece como uma doença subdiagnosticada entre os pacientes hospitalizados, com aproximadamente 25% dos casos associados à internação. OBJETIVOS: Avaliar as doenças associadas ao desenvolvimento de tromboembolismo pulmonar (TEP) diagnosticado em autópsias, e demonstrar a frequência de TEP como causa do óbito ou fator contributivo. MÉTODOS: Estudo caso-controle retrospectivo, realizado no Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1995 a 2004. Revisamos os relatórios diagnósticos das autópsias, identificando TEP fatal, quando TEP foi a causa de morte, e TEP não fatal, quando TEP foi doença associada. RESULTADOS: 1.506 pacientes (502 casos e 1.004 controles), 18.359 óbitos no período, média 2.040; 71,2% desses submetidos a autópsias. Observou-se importante declínio nas taxas de autópsias. De 1995-1999 (87,2%) e 2000-2004 (54,4%); p = 0,016. Dos 502 casos (3,8%), em 328 (2,5%) TEP foi causa de morte e 174 (1,3%), causa contributiva. Gênero: 51,6% homens e 48,4% mulheres. Idade: TEP fatal (328) vs controles (1.004), diferença estatisticamente significativa (p = 0,013). Condições prevalentes: câncer grupo, 31,4%, pós-operatório grupo, 17,2%, infecção grupo, 11,7%, e AVC grupo, 11%. Câncer de pulmão, 3,5%, câncer de cérebro e linfoma, 2,8%. Tempo de internação foi utilizado como indicador de imobilização. Outras doenças: AVCH (7,7%), pós-operatório de abdome (6,7%), pneumonia (5,9%), AVCI (3,1%) e pós-operatório vascular (4%) foram frequentes no grupo controle. Em contrapartida, aterosclerose (1,4%), ITU (1,2%), pós-operatório de ginecologia (0,8%), pós-operatório de obstetrícia (0,6%) e doença falciforme (0,6%) foram frequentes no grupo TEP. Cirrose, média de 14,9 dias de internação dos controles vs TEP com 4,4 dias (p < 0,001). Análise multivariada incluiu as condições com p 0,20 da univariada, idade e tempo de internação. Fator protetor para TEP: aneurisma de aorta (OR 0,02, IC 95% 0,46-0,56; p = 0,004), cirrose (OR 0,16, IC 95% 0,08-0,34; p < 0,001) e SIDA (OR 0,44, IC 95% 0,23-0,84; p = 0,013). Entretanto, AVCI (OR 1,82, IC 95% 1,04-3,19; p = 0,035), câncer de cérebro (OR 2,47, IC 95% 1,28-4,78; p = 0,007), câncer indeterminado (OR 3,12, IC 95% 1,01-9,68; p = 0,049), DPOC (OR 2,83, IC 95% 1,47-5,43; p = 0,002), ICC (OR 1,71, IC 95% 1,11-2,62; p = 0,015) e ITU (OR 4,34, IC 95% 1,05-17,82; p = 0,042) mostraram associação positiva com TEP. Idade vs TEP (OR 1,10, IC 95% 1,04-1,16; p = 0,001). Tempo de internação vs TEP (OR 1,19, IC 95% 1,05-1,36; p = 0,008). DISCUSSÃO: A porcentagem dos pacientes com TEP permanece inalterada, ocorrência de 4,1% e 3,4% no primero e no segundo períodos, com uma média de 3,8%. Em 50,4% dos pacientes não foi realizado o diagnóstico clínico de TEP. CONCLUSÃO: Constatou-se AVCI, câncer de cérebro indeterminado, DPOC, ICC e ITU com significância estatística e associação com TEP. Algumas fraquezas do presente estudo devem ser apuradas, e talvez explicarão as discordâncias com a literatura para algumas doenças. A identificação de fatores associados a TEP auxiliarão no diagnóstico precoce / INTRODUCTION: Literature shows that venous thromboembolism (VTE) remains as a sub-diagnostic disease among hospitalized patients, approximately 25% of all cases are associated to hospitalization. PURPOSE: Evaluate diseases associated to pulmonary thromboembolism (PE) development diagnosed in autopsies, and demonstrate the frequency of PE as cause of death or as a contributive factor. METHOD: The reports performed from 1995 to 2004 in a Brazilian tertiary referral medical school we reviewed for a retrospective study the autopsies diagnosis, identified as fatal PE, when PE was the cause of death and nonfatal PE, when PE was an associated disease. RESULTS: 1,506 patients (502 cases and 1004 controls), 18,359 deaths during the period, average 2,040; 71.2% of these were submitted to autopsies. It was observed an important decline in the autopsies rates. From 1995-1999 (87.2%) and 2000-2004 (54.4%) p = 0.016. From 502 cases (3.8%), 328 (2.5%) PE was the cause of death and 174 (1.3%) PE was contributive cause. Gender: 51.6% males and 48.4% females. AGE: fatal PE (328) vs controls (1,004) significant statistic difference (p = 0.013). Prevalent Conditions: cancer group, 31.4%, postsurgical group, 17.2%, infectious group, 11.7%, and CVA group, 11%. Pulmonary Cancer, 3.5%, Brain cancer and Lymphoma, 2.8%. Hospitalization period was taken as immobilization indicator. Other diseases: HCVA (7.7%), abdomen postsurgical (6.7%), pneumonia (5.9%), ICVA (3.1%) and vascular postsurgical (4%) were frequent in the control group. On the other hand, atherosclerosis (1.4%), UTI (Urinary Tract Infection) (1.2%), gynecology postsurgical (0.8%), obstetrics postsurgical (0.6%) and sickle cell anemia (0.6%) were frequent in the PE group. Cirrhosis, average of 14.9 hospitalization days of the controls vs PE with 4.4 days (p < 0.001). Logistic regression analysis includes the in univariated analysis with p 0.20, age and the hospitalization period. Protector factor for PE: Aortic aneurysm (OR 0.02, 95% CI 0.46-0.56; p = 0.004), cirrhosis (OR 0.16, 95% CI 0.08-0.34; p < 0.001) and SIDA (OR 0.44, 95% CI 0.23-0.84; p = 0.013). However, ICVA (OR 1.82, 95% CI 1.04-3.19; p = 0.035); brain cancer (OR 2.47, 95% CI 1.28-4.78; p = 0.007); undetermined cancer (OR 3.12, 95% CI 1.01-9.68, p= 0.049), COPD (OR 2.83, 95% CI 1.47-5.43; p = 0.002), CHF (OR 1.71, 95% CI 1.11-2.62; p = 0.015) and UTI (OR 4.34, 95% CI 1.05-17.82; p = 0.042), showed positive association with PE. Age vs PE (OR 1.10, 95% CI 1.04-1.16; p = 0.001). Hospitalization Period vs PE (OR 1.19, 95% CI 1.05-1.36; p = 0.008). DISCUSSION: The percentage of patients with PE remains unchanged, occurrence of 4.1% and 3.4% in the first and second periods, with an average of 3.8%. In 50.4% of the patients, the clinical diagnosis of TEP was not performed. CONCLUSION: We certified ICVA, brain cancer, undetermined cancer, COPD, CHF and UTI with significant association with PE. Some weaknesses of the present study should be refined, and maybe will explain the disagreement with the literature to some diseases. The identification of factors associated to PE will help in precocious diagnosis

OBJECTIVES: Clot in transit represents a life-threatening manifestation of venous thromboembolism of which we have limited understanding. This study was designed to describe the risk factors, clinical characteristics and outcomes associated with the development of a clot in transit as well as death within clot in transit patients. METHODS: We enrolled 1,093 consecutive patients into our single-center Pulmonary Embolism Response Team Registry. We compared 76 patients who had a clot in transit to 589 pulmonary embolism patients who did not have a clot in transit. RESULTS: Clot in transit was present in 11.4% of patients who received an echocardiogram to look for it. Multivariate analysis showed congestive heart failure (OR 2.954, 95% CI 1.349 – 6.467, P = 0.0068), a pre-existing inferior vena cava filter (OR 2.777, 95% CI 1.204 – 6.407, P = 0.0167), and hemodynamic collapse (OR 3.495, 95% CI 1.129 – 10.823, P = 0.0300) to be independent predictors of clot in transit. All-cause mortality by 30 days was higher in clot in transit patients (24.3% vs 9.7%, P < 0.001). All-cause mortality by 7 days within clot in transit patients was associated with hemodynamic collapse (45.5% vs 12.3%, P = 0.018) and mental status change (63.6% vs 21.5%, P = 0.008). CONCLUSIONS: The presence of congestive heart failure, a pre-existing inferior vena cava filter, and hemodynamic collapse are independent predictors of clot in transit and should alert physicians to patients who may require an echocardiogram. The mortality for clot in transit is high even when compared to a more severe pulmonary embolism population. Clot in transit represents a high-risk finding that may require more aggressive interventions. / 2020-06-14T00:00:00Z

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.