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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)
Protein C is the zymogen of a vitamin K-dependent serine protease involved in blood coagulation. In the absence of protein C the inactivation of activated factors V and VIIIC is impaired, and the fibrinolytic capacity of the circulating blood is reduced. These conditions promote excessive fibrin formation and thus constitute a risk factor for thrombosis.(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)
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)
To analyze the clinical manifestations of protein S deficiency, we evaluated 136 members of 12 families with the disorder. Seventy-one persons were found to be heterozygous for protein S deficiency, which is inherited as an autosomal dominant trait. Venous thrombotic events occurred in 39 patients (55%) and were recurrent in 77%. Most symptomatic patients(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)
A rabbit antibody against human protein C was used for the quantitative estimation of protein C in plasma. In healthy individuals protein C antigen ranged from 0.65-1.45 U/ml. Plasma protein C antigen was found to be independent of either age or sex. Under influence of oral anticoagulant treatment the protein C antigen concentration decreased to 0.47 U/ml(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)