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Activated protein C (APC) is a serine protease with potent anticoagulant properties, which is formed in blood on the endothelium from an inactive precursor. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa (ref. 2). To do this efficiently the enzyme needs a nonenzymatic cofactor, protein S (ref. 3).(More)
BACKGROUND A successful outcome of pregnancy requires an efficient uteroplacental vascular system. Since this system may be compromised by disorders of haemostasis associated with a prothrombotic state, we postulated that maternal thrombophilia might be a risk factor for fetal loss. We studied the relation between heritable thrombophilic defects and fetal(More)
CONTEXT Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN,(More)
Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70(More)
BACKGROUND The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of(More)
This article continues the review begun in a previous issue of the Journal, which considered the molecular basis and epidemiology of thrombophilia. In order to evaluate the contribution of genetic defects in the patho-genesis of thrombosis, the laboratory investigation should include a functional APC-R lest, determination of the factor V genotype and(More)
The risk factors for venous thrombosis differ from those for arterial vascular disease. During the past 5 years, knowledge about the aetiology of venous thrombosis has advanced with the discovery of several factors that contribute to the incidence of thrombosis, particularly the role of coagulation abnormalities. These abnormalities are common in the(More)
To elucidate the roles of the ABO blood group, von Willebrand factor (vWF), and clotting factor VIII in the process of deep-vein thrombosis we undertook a population-based patient-control study in which 301 consecutive patients younger than 70 with a first, objectively diagnosed episode of venous thrombosis and without an underlying malignant disorder were(More)
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes:(More)
We undertook a population-based case-control study to test the clinical importance of a hereditary abnormality in the coagulation system, characterised by poor anticoagulant response to activated protein C (APC), which is associated with familial thrombophilia. The abnormality was detected in 64 (21%) of 301 unselected consecutive patients younger than 70(More)