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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)
We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations(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)
Activated protein C (APC) resistance, determined with a thrombin-generation-based APC resistance test, may explain risk differences of venous thrombosis in users of second- and third-generation oral contraceptives (OC). To clinically validate this test, we analysed the Leiden thrombophilia case-control study (474 patients with a first episode of deep vein(More)
We report a C/T dimorphism in the thrombomodulin (TM) gene that predicts an Ala455----Val replacement in the sixth EGF-like domain of TM. This dimorphism has allelic frequencies of 82 (Ala) and 18% (Val) in a normal population. In a group of protein C deficient patients and in a group of subjects with unexplained thrombophilia the allelic frequencies were(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)
We investigated whether the occurrence of venous thrombosis in young women who use oral contraceptives might be explained by the factor V Leiden mutation, which leads to resistance to activated protein C and enhances susceptibility to thrombosis. We compared 155 consecutive premenopausal women, aged 15 to 49, who had developed deep venous thrombosis in the(More)
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen(More)
BACKGROUND A genetic variation located in the 3'-untranslated region of the prothrombin gene (prothrombin 20210 G-->A) was recently described as a risk factor for venous thrombosis. We examined how the presence of this mutation affected the risk of myocardial infarction in a population-based case-control study. Furthermore, we studied the risk of myocardial(More)
I n vivo, a delicate balance exists between fibrin formation and fibrinolysis. Reduced blood flow, changes in the vessel wall, and changes in blood composition (hypercoagulability) 1 may all result in a disturbance of this balance, which favors fibrin formation and ultimately may lead to the formation of occlusive thrombi. Venous thromboembolism is the(More)