Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Portal vein thrombosis is one of the main prehepatic causes of portal hypertension. The most frequent causes of thrombosis in this localization, apart from hepatic cirrhosis, are the following: acute inflammatory diseases and abdominal cancers, traumas, proliferative diseases of the hematopoietic system. In recent years attention was given to disorders in hemostasis, such as thrombophilia, in the course of which thrombosis development is particularly common. The authors present 10 patients after an incident of portal vein thrombosis, in which primary hepatic pathology was excluded and tests directed at thrombophilia were performed. In seven patients abnormalities in the examined parameters were found, and what is more, in two cases they had a complex character and involved more than one parameter. In five patients hyperhomocysteinemia was found. Among them, in two patients there was also a decreased protein S activity and in one of them there was also APC-resistance. In the next two patients there were abnormalities in one of the examined parameters - APC-resistance. Hyperhomocysteinemia was found in all patients with idiopathic thrombosis, and in one of them there were concurrent changes in protein S activity and APC-resistance. In patients with the history of portal vein thrombosis diagnostics of thrombophilia should be performed.
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PMID:[Portal vein thrombosis in patients with thrombophilia--own observations]. 1620 49

Testing for laboratory evidence of thrombophilia is now common but it has limited predictive value for the majority of unselected symptomatic patients. So when is testing indicated ? And which one? The term "thrombophilia" describes disorders of the haemostatic mechanisms which are likely to predispose to thrombosis. Thrombophilia may be heritable, acquired or mixed, resulting of the environment interacting with genetic background. To date, a limited number of genetic variants and other defects are proven to be independent risk factors for venous thromboembolism. These include antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia and antiphospholipid antibodies. There is no good evidence currently available to support the hypothesis that heritable thrombophilias increase the risk of arterial disease. But acquired or mixed thrombophilias such as hyperhomocysteinemia and antiphospholipid antibodies have been found in association with both venous and arterial thrombotic disorders. When testing for thrombophilia is indicated, especially in case of venous thromboembolism, it should include assays for heritable, mixed or acquired defects: deficiency of antithrombin, protein C or protein S, factor V Leiden and prothrombin G20210A mutations, elevated factor VIII, hyperhomocysteinemia and for antiphospholipid antibodies. Depending on the site of venous thrombosis, laboratory testing to exclude myeloproliferative disorders should be performed.
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PMID:[Venous thromboembolic disease: which coagulation screening, for whom, when?]. 1624 Aug 80

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.
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PMID:Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. 1628 82

Thrombophilia by definition represents acquired and/or genetic conditions that predispose patients to both venous and arterial thromboembolic events. Thrombosis is the most common cause of death worldwide. On the arterial side, myocardial infarction and stroke result in significant morbidity and mortality. Venous thromboembolic events most commonly involve the deep veins of the lower extremity with potential complications of pulmonary emboli. Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. With the description by Dahlback in 1993 of a condition initially labeled activated protein C resistance, significant advances have rapidly followed. Activated protein C resistance was linked to an underlying point mutation resulting in coagulation factor V (factor V Leiden). Recent attention has focused on certain inherited thrombophilic factors that may predispose to arterial and/or venous thromboses and their possible association with pregnancy complications, including early pregnancy loss. These include a group of mostly autosomal dominant, inherited gene mutations leading to a hypercoagulable state, such as factor V Leiden G1691A, factor II or prothrombin G20210A, and hyperhomocysteinemia associated with methylenetetrahydrofolate reductase C677T mutation. In addition, deficiencies in protein S, protein C, and antithrombin can lead to a hypercoagulable state. Although some studies of recurrent pregnancy loss patients with a positive test for an inherited thrombophilia are conflicting, a case-control study of untreated recurrent miscarriage patients who were heterozygous for the factor V Leiden mutation revealed a lower success rate than the controls who had a history of idiopathic recurrent miscarriage. With the identification of genetic risk factors, there has been synergistic amplification of thrombotic risk when one has an abnormal gene (e.g., factor V Leiden) plus environmental issues (e.g., pregnancy). Current understanding indicates that a combination of risk factors, including multiple inherited thrombophilic defects associated with secondary hypercoagulable states, have a particularly strong association with adverse pregnancy outcome.
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PMID:Thrombophilias and recurrent pregnancy loss. 1641 78

Hereditary thrombophilias are a group of inherited conditions that predispose to thrombosis. Mutations like factor V Leiden, prothrombin gene variant 20210A, and hereditary hyperhomocysteinemia are associated with an increased risk for thromboembolism as compared to mutations in natural inhibitors of coagulation. There is also evidence that multiple defects co-exists in persons with a tendency for thrombosis. We studied prothrombotic determinants, namely protein C, protein S, and AT along with factor V Leiden (1691G-->A), prothrombin gene mutation (20210G-->A), CBS 844ins68 mutation, and MTHFR mutation (677C-->T) in consecutive ethnic Omani patients with first episode of a thrombophilic event, namely, deep vein thrombosis (DVT), and/or pulmonary embolism (PE) or thrombosis at an unusual site. Fasting plasma homocysteine was also analyzed. Factor V Leiden and the prothrombin gene mutation were not seen in any patient nor in any control subject studied. The thermolabile MTHFR mutation (677C-->T) was present in 14 patients (35.89%) whereas the CBS 844ins68 mutation was documented in 6 patients (15.38%); 3 patients were common in both groups. Six patients had low protein C (15.38%), two patients had low protein S (5.12%), but none had low AT levels. Interestingly, one patient had triple abnormality, namely, PC deficiency with both CBS 844ins68 mutation as well as the MTHFR mutation (677C-->T) whereas another two patients had the latter two mutations together. This data set, although small, reflects the importance of multiple screening strategies. The yield appears high, emphasizing the referral pattern to a tertiary health center. Of these patients, 43.58% had either or both the hyperhomocysteinemic mutations studied, whereas in 38.46% of these patients, no underlying cause for thrombophilia could be documented.
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PMID:Hereditary thrombophilia in ethnic Omani patients. 1643 49

Inherited thrombophilia can be defined as a genetically determined predisposition to the development of thromboembolic complications. Since the discovery of activated protein C resistance in 1993, several additional disorders have been described and, at present, it is possible to identify an inherited predisposition in about 60 to 70% of patients with such complications. These inherited prothrombotic risk factors include qualitative or quantitative defects of coagulation factor inhibitors, increased levels or function of coagulation factors, defects of the fibrinolytic system, altered platelet function, and hyperhomocysteinemia. In this review, the main inherited prothrombotic risk factors are analyzed from epidemiological, laboratory, clinical, and therapeutic points of view. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in particular conditions such as childhood and pregnancy.
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PMID:Inherited thrombophilia. 1657 55

Our objective was to characterize the etiologic factors and outcome for stroke in children. We retrospectively reviewed the charts of patients between the ages of 40 days and 94 months (36.5 +/- 23.7 months) with stroke seen at Istanbul Medical Faculty, Department of Pediatrics between January 1995 and December 2003. We found 79 cases of stroke: 57 ischemic and 22 hemorrhagic strokes. Seventeen children had vitamin K deficiency dependent hemorrhage. In 14 children stroke occurred as a complication of cardiac disease, 7 had moyamoya disease, 3 had protein C deficiency, 2 had thalassemia, 2 had hyperhomocysteinemia (methylene tetrahydrofolate reductase gene mutation), 2 were heterozygote for factor V Leiden, 3 had Down's syndrome, 1 was diagnosed with antiphospholipid syndrome, 1 had glycogen storage disease, and in 28 children no underlying cause could be found. Multiple risk factors were found in 4 children. The outcome in all 79 stroke patients was as follows: asymptomatic 60%; symptomatic epilepsy or persistent neurologic deficit 37%; death 3%; and recurrent stroke 5%. Thus, an underlying cause for stroke was identified in 65% of the children in the study group; 40% of the children either died or suffered motor and/or cognitive sequelae.
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PMID:Stroke in childhood: experience in Istanbul, Turkey. 1663 11

The identification of constitutional and/or acquired risk factor is of major importance in the treatment of thromboembolic disease in young people; it contributes to evaluate the risk of recurrence and to define the period of oral prophylactic anticoagulant treatment. Several congenital or acquired abnormalities of haemostasis are actually defined. In this paper, we report the case of a 34-year-old man who developed a deep venous thrombosis, five months before the diagnosis of megaloblastic anemia, probably due to pernicious anemia. The thrombosis was partially explained by the acquired hyperhomocysteinemia induced by vitamin B12 deficiency. Moreover, activated protein C resistance due to factor V Leiden, was revealed in our patient. This latter improved under anticoagulant treatment combined with vitamin B12. Combination in one individual, of different risk factors predisposing to inherited and/or acquired thrombophilia, results in increased risk for thrombo-embolic disease, suggesting synergic interaction between these factors.
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PMID:[Association of tow thrombotic risk factors: factor V Leiden and hyperhomocysteinemia. A case report]. 1670 35

Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects.
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PMID:Inherited and acquired thrombophilia: pregnancy outcome and treatment. 1679 17

Hyperhomocysteinemia is a risk factor for thrombosis, but the mechanisms are not well defined. We tested the hypothesis that hyperhomocysteinemia accelerates arterial thrombosis in mice. Mice heterozygous for a targeted disruption of the cystathionine beta-synthase gene (Cbs+/-) and wild-type littermates (Cbs+/+) were fed either a control diet or a high methionine/low folate (HM/LF) diet for 6 to 8 months to produce graded hyperhomocysteinemia. The time to occlusion of the carotid artery after photochemical injury was shortened by more than 50% in Cbs+/+ or Cbs+/- mice fed the HM/LF diet (P < .001 versus control diet). Carotid artery thrombosis was not accelerated in mice deficient in endothelial nitric oxide synthase (Nos3), which suggests that decreased endothelium-derived nitric oxide is not a sufficient mechanism for enhancement of thrombosis. Cbs+/+ and Cbs+/- mice fed the HM/LF diet had elevated levels of reactive oxygen species in the carotid artery, increased aortic expression of the NADPH oxidase catalytic subunit, Nox4, and decreased activation of anticoagulant protein C in the aorta (P < .05 versus control diet). We conclude that hyperhomocysteinemia enhances susceptibility to arterial thrombosis through a mechanism that is not caused by loss of endothelium-derived nitric oxide but may involve oxidative stress and impairment of the protein C anticoagulant pathway.
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PMID:Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia. 1680 15


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