Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.

Thèse d'exercice : Médecine. Médecine générale : Nantes : 2007. / Bibliogr.

Reproduction de : Thèse d'exercice : Chirurgie dentaire : Nantes : 2008. / Bibliogr.

Background: Advance in cardiac intervention improved the survival of patients with congenital heart diseases (CHD). However, they may have propensity of thromboembolism and the use of antithrombotic agents was generally based on small studies and consensus opinion. Objective: To systematically review the current literature on the efficacy and safety of various antithrombotic agents in patients with CHD. Methods: Studies published in English during the period 1990 – 2012 were identified using keyword search from PubMed, Medline, EMBase, and Cochrane Library. Additional search from reference sections of the articles and clinical trial registry was performed. Data extracted included: type of studies, number of patients, follow-up period during which the patients were on the antithrombotic agents, number of thromboembolic (TE) events, and all, major and minor bleeding events. Event rate as the proportion of events of the patients and event per 100 patients-year were obtained for respective antithrombotic agent in each study. Composite event rate and event per 100 patients-year were estimated after weighting. Results: Forty studies consisted of 5144 patients were reviewed. Observation period of 8916.6 years was available in 25 studies. Diagnostic categories included: Fontan operation 15, systemic-to-pulmonary artery shunt 7, mechanical valve 8, atrial septal defect occlusion device 2, cyanotic heart 1, mixed 7. Antithrombotic prophylaxis was not used in 13 studies, warfarin in 26, aspirin alone in 22, combined aspirin and dipyridamole in 2. Clopidogrel with concomitant antithrombotic agents was reported in 5 studies. Overall composite TE event rate was 3.9% (95% CI 2.3 – 5.4%) and that of all bleeding rate was 2.8% (95% CI 0 – 5.5%), with 1.4% (95% CI 0.0 – 2.6%) for major and 2.2% (95% CI 0.0 – 4.3%) for minor bleeding. Composite TE rate for no prophylaxis (9.6%; 05% CI 3.7 – 15.5%) was significantly greater than that of warfarin (1.7%; 95% CI 0.1 – 3.3%) and aspirin (1.3%; 95% CI 0.0 – 3.0%). Both TE and all bleeding rate showed no difference between warfarin and aspirin, while major bleeding tended to be higher in warfarin than aspirin(0.9% vs 0.0%, p=0.06). Fontan patients had overall TE rate of 2.7% (95% CI 0.1 – 5.4%). Patients with no prophylaxis (10.2%; 95% CI 9.2 – 18%) had significantly greater TE rate than warfarin (1.4%; 95% CI 0.0 – 0.4%) or aspirin (1.2%; 95% CI 0.0 – 3.0%). All bleeding rate in Fontan patients was 0.5% (95% CI 0.0 – 4.3%). Both TE ad bleeding rates showed no difference between warfarin and aspirin. Overall TE rate for shunt was 7.2% (95% CI 3.7 – 14.3%), being similar between aspirin group and no antithrombotic group. Patients with mechanical valves had TE rate of 7.3% (95% CI 2.9 – 11.6%) and all bleeding rate of 7.2% (95% CI 4.2 – 10.2%). There was no statistical difference between warfarin and APA group. Patients with ASD occlusion device has TE rate of 0.1% (95% CI 0.0 – 0.2%). No bleeding event was reported in the studies. Conclusion: Patients with congenital heart diseases were at risk of developing thromboembolism which justified the use of anti-thrombotic prophylaxis. Further studies relating the thromboembolic risk profile of patients with CHD to the efficacy of anti-thrombotic agents might help in selection of anti-thrombotic agents. / published_or_final_version / Community Medicine / Master / Master of Public Health

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 5 uppsatser.

Thesis (M. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 177-207) Also available in print.

Thesis (M.S.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 45-49). Also available on the World Wide Web.

Thesis (Ph.D.)--University of Melbourne, School of Nursing and Social Work, Dept. of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, 2009. / Typescript. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1948. / Typescript. Vita. With this is bound: Studies on the hemorrhagic sweet clover disease : XIII. Anticoagulant activity and structure in the 4-hydroxycoumarin group / By Ralph S. Overman ... David G. Doherty, et. al. Reprinted from Journal of biological chemistry, vol. 153, no. 1 (Apr. 1944), p. 5-24. Includes bibliographical references.

Thèse--Méd.--Reims, 1973. N°: N° 13. / Bibliogr. ff. 52-60.