C. Caram-Deelder’s thesis explores the potential of secondary data – data that was generated for a different purpose than the research itself - to answer questions regarding safety and efficacy of... Show moreC. Caram-Deelder’s thesis explores the potential of secondary data – data that was generated for a different purpose than the research itself - to answer questions regarding safety and efficacy of blood products. By combining datasets of several hospitals, she demonstrated that receiving red cell transfusions from a female donor who has been pregnant is associated with increased mortality among male patients under the age of 50. Also using data from hospitals she demonstrated that old platelets shorter the time between platelets transfusions, resulting in an increased total number of transfusions on a population level. This increase is, however, unlikely to outweigh the benefit of reduced outdating and wastage. By meta-analysing studies it is shown that old platelets are inferior to fresh platelets for platelet related counts, time between transfusions and the need of additional platelet transfusions. Additionally the thesis discusses the methodological issue of the use of the terms ‘prospective’ and ‘retrospective’ in clinical observational research. These terms are still broadly used in spite of the recommendation to refrain from using them by guidelines and journals’ editorial boards. The usage of the terms was, however, not associated with the quality of the report. Show less
Several studies during the past decade have shown that patients with venous thrombosis have an increased risk of subsequent arterial thrombosis, thus suggesting a link between the two diseases. The... Show moreSeveral studies during the past decade have shown that patients with venous thrombosis have an increased risk of subsequent arterial thrombosis, thus suggesting a link between the two diseases. The aim of this thesis was to investigate the associations of traditional cardiometabolic risk factors with risk of a first and recurrent venous thrombosis. We showed that levels of major lipids, i.e. total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides, were not associated with a first venous thrombosis. In contrast, low levels of apolipoproteins B and A1 were associated with an increased risk of a first event. Regarding recurrence, tests for lipid levels, glucose levels and hematologic variables did not identify patients at an increased risk of recurrent venous thrombosis, and these tests should not be done for this indication nor influence decisions on duration of anticoagulant treatment. In this thesis, we further searched for associations between lipids and hemostatic factors, and found that levels of vitamin K-dependent factors (VKDFs), including factor IX, were associated with triglyceride levels. We hypothesized that this association could be explained by common mechanisms, regulating levels of both VKDFs and triglycerides. Show less
This thesis reports on studies that have investigated the role of several factors on the risk of arterial thrombosis. The thesis is organised in two sections. The first section (Chapters 2-5)... Show moreThis thesis reports on studies that have investigated the role of several factors on the risk of arterial thrombosis. The thesis is organised in two sections. The first section (Chapters 2-5) deals with risk factors for the first arterial thrombotic event whereas the second section (Chapters 6 and 7) concerns risk factors for recurrence. The investigations touch several aspects of epidemiology, and make use of several observational study designs, encompassing case control, cohort and meta-analysis. Several statistical models were also applied ranging from logistic regression models, Cox proportional hazards time to event regression models as well as non-parametric statistics. Because of the heterogeneous nature, each investigation had specific problems in study design, data collection and analyses. A common line, however, is the haemostatic balance and its markers. Taken together, the findings of this thesis lead to the conclusion that there are differences in the aetiology of the two main forms of arterial thrombosis. Indeed, they support the hypothesis that hypercoagulability plays a greater role in the pathogenesis of ischaemic stroke than in that of myocardial infarction. Show less
The overall goal of this thesis was to identify patients who are at high risk for major bleedings during anticoagulant treatment and to reduce the number of major bleeds. The first part looks... Show moreThe overall goal of this thesis was to identify patients who are at high risk for major bleedings during anticoagulant treatment and to reduce the number of major bleeds. The first part looks into methodology of observational studies. It shows that biases in observational studies may be an explanation why statins seem to have many unintended effects. The second part looks into bleeding complications and shows that patient with three concomitant anticoagulants experience high major bleeding rates. Also, a study was performed in which plasma and DNA of participants was collected, to identify risk factors for major bleeds in the future. The first results show that damage to vessel walls increases the risk of major bleeding. Interventions to reduce the number of bleeding events were to dose nadroparin od instead of bid. In addition, multi-dose drug dispensing may increase adherence of medication. Also, vitamin K1 tablets are easier to ingest and this thesis shows that the tablets are as effective in reducing the INR as the oral solution. Show less
Patients with deep vein thrombosis or pulmonary embolism remain at risk for recurrent venous thrombosis. This risk is pronounced in the first months after the acute episode and declines in... Show morePatients with deep vein thrombosis or pulmonary embolism remain at risk for recurrent venous thrombosis. This risk is pronounced in the first months after the acute episode and declines in subsequent years. Although the existence of an extensive list of risk factors may seem reassuring, it does not come close to give us all the answers: many people have several of these risk factors but never develop thrombosis; others suffer from thrombosis but have none. Therefore, the challenge that we are facing today is not to just add more risk factors to this list but rather to integrate them all in a causal model that allows us to understand how and when thrombotic disease develops. The idea behind “the thrombosis potential model” is that an individual is at risk for venous thrombosis throughout life, which is reflected in the ‘thrombosis potential’ and that each risk factor contributes to increase the potential. Only when the combination of thrombosis risk factors reach a certain potential, venous thrombosis will occur. In this thesis, the thrombosis potential model will be applied to several known risk factors for venous thrombosis to better understand why first and recurrent venous thrombosis can develop in an individual patient. Show less
