Isolated distal deep vein thrombosis (IDDVT) is a condition recently suggested to be a different entity to that of proximal disease. There is currently little evidence defining the clinical importance of detection and treatment. International guidelines vary regarding management advice.An observational cohort study, prospective service evaluation and pilot randomised controlled trial were performed within a United Kingdom ambulatory thrombosis service. This project aimed to describe the burden of disease and explore three poorly researched aspects of IDDVT assessment and management: whole-leg compression ultrasound (CUS) performed by non-physicians within an ambulatory framework as a principal diagnostic modality; clinical presentation data and risk profile in comparison to that of proximal disease; the feasibility of further interventional randomised research and the risk/benefit profile of therapeutic anticoagulation.Within this ambulatory cohort, IDDVT accounted for 49.7% of acute thrombosis and differed significantly to proximal disease regarding provocation and symptomatology at clinical presentation. A negative whole-leg CUS excluded deep vein thrombosis with an adverse event rate (diagnosis of symptomatic venous thromboembolism during the 3 month follow up period) of 0.47% (95% CI 0.08 to 2.62). Future interventional research was proved feasible within an ambulatory setting.The randomised controlled trial conducted within this project is the largest to date comparing therapeutic anticoagulation against conservative strategy for the management of acute IDDVT. Patients allocated to therapeutic anticoagulation had significantly less overall propagation of thrombus (Absolute risk reduction [ARR] 25.7%, 95% Confidence interval 5.9 to 44.3 p<0.01), less short-term symptomatic progression (ARR 16.7%, 95% CI 2.6 to 32.1 p=0.05) and a result trending towards significance for reduction in serious thromboembolic complications (ARR 11.4%, 95% CI -1.5 to 26.7 p=0.11).IDDVT is a condition of equal prevalence to proximal venous thrombosis, which varies significantly regarding risk profile and clinical presentation. Using a single whole leg CUS reported by a non-physician within an emergency department pathway is associated with a low adverse event rate. This contemporary data also suggests that therapeutic anticoagulation is beneficial for reduction of short-term complications in IDDVT. The risk of false positive diagnosis and excess anticoagulation remains.This data can inform and direct future design of adequately powered randomised studies, in order to attempt external validation of these findings.

by Liu Kin Hung. / Thesis submitted in: Dec, 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 87-95). / Abstract also in Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Literature Review --- p.3 / Chapter 2.1 --- Venous anatomy --- p.3 / Chapter 2.2 --- Arterial anatomy --- p.6 / Chapter 2.3 --- Deep vein thrombosis --- p.8 / Chapter 2.3.1 --- Clinical Examination --- p.11 / Chapter 2.3.2 --- Contrast Venogram --- p.12 / Chapter 2.3.3 --- Color duplex ultrasound --- p.13 / Chapter 2.4 --- Arterial resistance --- p.24 / Chapter 2.5 --- Basis for study --- p.28 / Chapter 3 --- Method --- p.30 / Chapter 3.1 --- Subjects --- p.30 / Chapter 3.2 --- Equipments --- p.30 / Chapter 3.3 --- Procedure --- p.31 / Chapter 3.4 --- Data analysis --- p.38 / Chapter 4 --- Results --- p.40 / Chapter 4.1 --- Arterial resistance changes in different groups --- p.40 / Chapter 4.1.1 --- Symptomatic with no DVT versus asymtomatic with no DVT --- p.40 / Chapter 4.1.2 --- Symptomatic with DVT versus symptomatic with no DVT --- p.43 / Chapter 4.1.3 --- Symptomatic acute DVT versus symptomatic chronic DVT --- p.46 / Chapter 4.1.4 --- Symptomatic proximal-DVT versus symptomatic calf-DVT --- p.49 / Chapter 4.1.5 --- symptomatic occlusive DVT versus symptomatic non- occlusive DVT --- p.52 / Chapter 4.2 --- Diagnosis of DVT by arterial resistance changes --- p.57 / Chapter 4.2.1 --- Detection of presence of symptomatic DVT --- p.57 / Chapter 4.2.2 --- Differentiation of characteristics of symptomatic DVT --- p.60 / Chapter 5 --- Discussion --- p.64 / Chapter 5.1 --- Investigation of arterial resistance changes --- p.64 / Chapter 5.1.1 --- Symptomatic with no DVT versus asymtomatic with no DVT --- p.66 / Chapter 5.1.2 --- Symptomatic with DVT versus symptomatic with no DVT --- p.69 / Chapter 5.1.3 --- Symptomatic acute DVT versus symptomatic chronic DVT --- p.72 / Chapter 5.1.4 --- Symptomatic proximal-DVT versus symptomatic calf-DVT --- p.74 / Chapter 5.1.5 --- symptomatic occlusive DVT versus symptomatic non- occlusive DVT --- p.76 / Chapter 5.2 --- Detection and differentiation of DVT by arterial resistance --- p.80 / Chapter 5.2.1 --- Detection of symptomatic DVT --- p.80 / Chapter 5.2.2 --- Differentiation of occlusive DVT from non-occlusive DVT --- p.82 / Chapter 6 --- Conclusion --- p.85 / Chapter 7 --- References --- p.87

No description available.

Superficial venous thrombosis (SVT) is a common inflammatory and thrombotic pathology occurring within a superficial vein. SVT can result in distressing symptoms of redness and pain in the affected area and exposes patients to a risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Various therapeutic options are available to patients including anti-inflammatories, anti-coagulation and surgical procedures, however which of these therapies is the best first line treatment remains unknown. Several randomized controlled trials have been conducted addressing this question, yet methodological and design flaws have limited the translation of their results into a change of clinical practice. The following thesis consists of a multi-step process of reviewing the evidence to date followed by a process of engaging with clinician stakeholders with the goal of designing a randomized control trial that would provide a meaningful answer to patients and their clinicians. In the first step of this process, a systematic review of the literature was performed, including a meta-analysis to estimate pooled risk of developing symptomatic venous thromboembolic (VTE) complications in patients with isolated SVT following various treatments. These results were then presented to expert Canadian clinicians in a series of surveys using a Delphi process to determine the clinical trial design that would have the greatest impact on changing clinical practice. An additional survey of expert clinicians was conducted to determine current practice variation in the diagnosis, management, and follow up of patients with SVT, in order to design a clinical trial that best reflected current standard Canadian clinical practice. Our systematic review identified 15 articles and including 5775 patients. Quality and assessment of risk of bias was moderate for most included studies. The findings of our meta-analysis identified that Fondaparinux, at prophylactic dose, to had the lowest event rate of 2.0 events per 100 patient years of follow-up (95% CI 0.4 to 4.7, I2=33%) for the primary outcome of deep vein thrombosis (DVT) or pulmonary embolism (PE) during follow-up. Pooled event rates ranged from 8.6-16.6 events per 100 patient-years across other treatment categories, including placebo/observation only, with an event rate of 10.5 events per 100-patient years (95% CI 3.0 to 22.0). Heterogeneity was moderate to high for most pooled estimates, limiting the interpretation of these findings. Our survey of practice variation among expert Canadian clinicians revealed wide practice variation in in diagnosis and therapeutic management including sub-groups (e.g. cancer). There was agreement that clinical equipoise exists for the optimal treatment of SVT (77% of respondents), supporting the need for further research. Two rounds of surveys were performed using Delphi process methods, resulting in consensus for the design of a future randomized control trial (RCT). The agreed on design was for a randomized control trial comparing a direct oral anticoagulant (DOAC) such as Rivaroxaban, to Non-Steroidal Anti-Inflammatories (NSAIDs), using a non-inferiority RCT design with a non-inferiority margin of 3%. Future direction of this research will be to continue stakeholder engagement by engaging patients in the clinical trial design, followed by development of a pilot RCT protocol and application for peer-reviewed funding.

Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.

Background. Growth-arrest specific 6 (gas6) is a novel vitamin-K dependent protein whose role in venous thromboembolism was recently characterized in murine models. Gas6 is suggested to be a prothrombotic protein capable of mediating thrombus stability. However, the association between gas6 and venous thromboembolism has yet to be elucidated in humans. The present work aims to delineate the existence of such an association in humans and propose a mechanism by which gas6 expression is related to venous thromboembolic disease. / Methods. To analyze the association between gas6 and venous thromboembolism, a highly specific ELISA method was used to measure plasma gas6 levels in 306 patients with a history of deep-vein thrombosis (DVT) and 89 control volunteers. Medication history, comorbid conditions and DVT characteristics were documented for the purposes of statistical analyses. Median gas6 levels were compared between the subgroups, and prevalence rate ratios were calculated. Human umbilical vein endothelial cells were used to measure the effect of gas6 treatment on the expression of various mediators of coagulation. Murine thrombosis models were developed to serve as in vivo models for thrombosis. / Results. The median levels of gas6 were 28.21 ng/ml in patients compared to 26.15 ng/ml in controls (p=0.01). After adjustment for age, sex, comorbidity and medications, DVT patients had a PRR of 2.5 (95% CI 1.36 to 4.61, p=0.003) compared with controls. Within the DVT subgroup, median gas6 levels were significantly higher in those with cancer-associated (vs. unprovoked or secondary) DVT (p&lt;0.001) and in those with more extensive DVT (p=0.037), while levels were significantly lower in those taking warfarin (vs. no warfarin) (p=0.03). Preliminary results with endothelial cell cultures are inconclusive with regards to the effect of gas6 on endothelium derived mediators of coagulation. / Conclusions. Elevated plasma gas6 is associated with venous thromboembolism. The etiology of the clot influences detected levels of gas6, with the highest levels seen in cancer-patients. Furthermore, increasing clot burden correlates with elevated levels of gas6. A mechanistic explanation for how gas6 modulates this association is in its preliminary stages, and is worth pursuing.

Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Background: Up to 40% of trauma patients die during the first 24 hours after injury due to massive hemorrhage. In patients who survive this critical time period, no information is available on rates of delayed major bleeding or factors associated with delayed major bleeding. Methods: A retrospective chart review of 150 critically ill adult trauma patients was used to determine the incidence of delayed major bleeding events. Cox proportional hazards multivariate analysis was performed to assess for risk factors associated with delayed major bleeding events. The anticipated rate of delayed major bleeding events was 10%. Results: The incidence of delayed major bleeding in this cohort of critically ill trauma patients was 44%. Predictors that were statistically significantly associated with delayed major bleeding included: male gender, pre-injury use of the antiplatelet agents aspirin and/or clopidogrel, presence of intracranial bleeding, higher injury severity scores, requirement of massive transfusion, and low pH values. Use of anticoagulant prophylaxis was not associated with delayed major bleeding. Conclusion: The rate of delayed major bleeding was higher than estimated. Larger retrospective and prospective cohorts are needed to confirm these findings.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Pharmacy Johannesburg 2001. i / The use of a low molecular weight heparin, enoxaparin was evaluated in the prevention and treatment of deep vein thrombosis. Patterns of use were analysed and measured against pre-determined criteria with a view to promoting optimal use and identifying those factors, which may contribute to safer use of the drug. / IT2018