Patients with lower leg cast immobilization or who had knee arthroscopy have an increased risk of venous thrombosis. Because of this increased risk, thromboprophylaxis was given to the majority of... Show morePatients with lower leg cast immobilization or who had knee arthroscopy have an increased risk of venous thrombosis. Because of this increased risk, thromboprophylaxis was given to the majority of these patients in the Netherlands, despite insufficient evidence for its effect. In this thesis, two large randomized controlled trials (including 1500 patients each, in which half of patients were randomized to prophylaxis with Low Molecular Weight Heparin (LMWH) and half of patients to no treatment) are described. Despite having an increased VTE risk, routine thromboprophylaxis with low dose LMWH did not decrease VTE risk in these patients. Therefore, we recommend no routine thromboprophylaxis with anticoagulants to these patients. Identification of high-risk patients and selective treatment of patients can be beneficial. Therefore, prediction models for the development of VTE in these patients were developed. The prediction models had good predictive value and were validated in two other studies. Hence, identification of high-risk patient can help to optimize prophylactic treatment: providing a higher dose or longer duration of anticoagulant treatment to patients with an additionally increased risk, whilst patients with a low risk will not be needlessly exposed to the burden and risk of anticoagulants. Show less
Cancer patients have a four- to sevenfold increased risk of developing cancer-associated thrombosis (CAT), which is associated with a strong increase in morbidity and mortality. Not all cancer... Show moreCancer patients have a four- to sevenfold increased risk of developing cancer-associated thrombosis (CAT), which is associated with a strong increase in morbidity and mortality. Not all cancer patients receive thromboprophylaxis as this may lead to adverse events in a cancer population that is already at increased risk for major bleedings. Different risk prediction models have been developed to identify cancer patients at high risk of developing CAT that may be selected for thromboprophylaxis. However, risk models using the currently established biomarkers and clinical parameters perform poorly, particularly when validated in independent cohorts. Discovery of new and better biomarkers are therefore urgently needed. This review describes how aberrations in the genetic profile of the tumor and host influence a hypercoagulable state, and explores how these can be used as novel biomarker to improve CAT risk prediction. Show less
Background: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to... Show moreBackground: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study.Methods: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat.Results: In multivariable adjusted analyses a 1 mu g/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses.Discussion: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant. Show less
