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)

Cerebral venous thrombosis is a polymorphic clinical entity for which diagnosis has become more frequent with the advent of neuroradiology. The superior sagittal and transverse sinuses are frequently involved, whereas cavernous sinus thrombosis is much less frequent. Inherited resistance to the anticoagulant action of activated protein C (APC resistance), antithrombin deficiency, protein C and S deficiencies, and hyperhomocysteinemia seem to represent major causes of thrombophilia when unusual thromboembolic events (ie, before the age of 45 years) are observed. The authors present the combined occurrence of protein C and protein S deficiencies in a 32-year-old woman, manifested by extensive cerebral venous thrombosis.
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PMID:Cerebral venous thrombosis and procoagulant factors--a case study. 967 56

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from two to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and activated protein C resistance have synergistic effect on the onset of thrombotic disease. Recent studies with animal models for mild hyperhomocysteinemia provided encouraging results in the understanding of the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. These animal models pointed to the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.
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PMID:Relationship between homocysteine and thrombotic disease. 970 66

The proteolytic enzyme activated protein C (APC) is a normal plasma component, indicating that protein C (PC) is continuously activated in vivo. High concentrations of homocysteine (Hcy) inhibit the activation of PC in vitro; this effect may account for the high risk for thrombosis in patients with hyperhomocysteinemia (HyperHcy). We measured the plasma levels of APC in 128 patients with previous venous thromboembolism (VTE) and in 98 age- and sex-matched healthy controls and correlated them with the plasma levels of total Hcy (tHcy) measured before and after an oral methionine loading (PML). Forty-eight patients had HyperHcy and 80 had normal levels of tHcy. No subject was known to have any of the congenital or acquired thrombophilic states at the time of the study. Because the plasma levels of APC and PC were correlated in healthy controls, the APC/PC ratios were also analyzed. Plasma APC levels and APC/PC ratios were significantly higher in VTE patients than in controls (P=0.03 and 0.0004, respectively). Most of the increase in APC levels and APC/PC ratios were attributable to patients with HyperHcy. Patients with normal tHcy had intermediate values, which did not differ significantly from those of healthy controls. There was no correlation between the plasma levels of tHcy or its PML increments and APC or APC/PC ratios in controls. The fasting plasma levels of APC and APC/PC ratios of 10 controls did not increase 4 hours PML, despite a 2-fold increase in tHcy. This study indicates that APC plasma levels are sensitive markers of activation of the hemostatic system in vivo and that Hcy does not interfere with the activation of PC in vivo.
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PMID:Plasma levels of activated protein C in healthy subjects and patients with previous venous thromboembolism: relationships with plasma homocysteine levels. 974 24

Thromboembolic disease results from an hypercoagulable state and multifactorial causes may lead to hypercoagulability. Thrombogenic risk factors can be acquired and/or inherited. For each thrombophilic patient, the main clinical features retained are: the patient age, the familial history, the recurrence of thromboembolic events, an unusual site of thrombosis. Anti-phospholipid antibodies, which are considered as acquired thrombogenic risk factors, can be detected with coagulation tests and/or Elisa methods. The association of antiphospholipid antibodies with thrombosis is defined as the anti-phospholipid syndrome. Last decades, genetic risk factors were identified. First of all, antithrombin, protein C and protein S deficiencies were described. These deficiencies are involved in about 10% of patients who develop thrombosis before the age of 50. In 1993, a new genetic risk factor was discovered: activated protein C resistance which is due to the Q506 mutation in factor V. This defect represents the most prevalent abnormality of inherited thrombophilia, affecting 20 to 40% of thrombophilic patients. Interestingly, hyperhomocysteinemia, known as potentially predisposing to arterial disease, was also recognized as a risk factor for venous occlusive disease. Several genes encoding homocystein metabolism enzymes, such as cystathionine beta-synthase or methylenetetrahydrofolate reductase are concerned. Establishment of a causal association between the presence of a biological abnormality and the occurrence of thrombosis may lead to an adapted prophylaxis whatever the risk situation.
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PMID:[Evaluation of hemostasis in venous thromboembolism pathology]. 975 22

In the past two decades, several mechanisms leading to thrombophilia have been elucidated, and corresponding laboratory tests developed. At a time of financial constraints, it is crucial to distinguish between the tests of proven value (which can modify the therapeutic attitude toward the patient and/or his family) from those of unproven value. We have listed in the first category determination or measurement of factor V Leiden, factor II G20210A, antithrombin, protein C, protein S, as well as antiphospholipid antibodies and hyperhomocysteinemia. A combined clinical and laboratory approach taking into account the history of the patient and his family, the prevalence of the defects, and also the accuracy of the tests should allow tailoring a laboratory testing program to each individual patient. It is essential to keep in mind that the more difficult task is not to perform the tests, but to consider who will benefit from testing both for prevention and therapy of venous thromboembolism. The present review provides answers to some of these issues. These answers should, however, be considered as provisional because new findings and study results will certainly modify them in the future.
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PMID:Screening test for thrombophilic patients: which tests, for which patient, by whom, when, and why? 976 49

Inherited resistance to activated protein C (APC) has been recently recognized as a novel cause underlying venous thrombophilia. In most cases APC resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Factor V Leiden allele is present in about 5% of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is virtually absent in Africans, Asians, and races with Asian ancestry such as Amerindians, Eskimos, and Polynesians; this suggests a single origin of the mutation, which has been proven by haplotype analysis. A low prevalence of the mutation (1%) was noticed in African-Americans for recent racial admixture. Factor V Leiden presents not a major role as risk factor for arterial thrombosis, while it is present in 18% of Caucasian patients with venous thrombosis. This high incidence prevalence mirrors the incidence in the corresponding general populations and can be even higher in some areas according to the ethnic background. Conversely, factor V Leiden is usually not found in non-Caucasian thrombotic patients; this could give reason of the lower incidence of venous thrombotic disease in Africa and Asia in comparison with Europe. Therefore, screening for factor V Leiden is suggested for all Caucasian individuals with previous venous thrombosis; inclusion criteria for the screening should not be stringent because clinical manifestations associated with the mutant genotype can be also mild or secondary to circumstantial risk factors or manifesting at advanced age. Factor V Leiden can act also as concurrent risk factor in individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia. So far, screening for the mutation in individuals with no history of thrombosis is recommended only for relatives of proband patients identified as carriers; the available data do not justify indiscriminate screening before risk situations such as oral contraceptives intake, pregnancy, or high-risk surgery.
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PMID:Epidemiology of factor V Leiden: clinical implications. 976 54

Thrombophilic states are a group of conditions associated with increased predisposition to thromboembolic events. The well-recognized inherited thrombophilic states include resistance to activated protein C (APC) (Factor V Leiden) and deficiencies of plasma antithrombin, protein C, and protein S. These entities are aberrations in the natural anticoagulant systems that exist in plasma and at the endothelial cell level. Other causes of inherited thrombophilia include hyperhomocysteinemia, abnormalities in the proteins of the fibrinolytic system, dysfibrinogenemias, deficiency of heparin cofactor II, abnormal thrombomodulin, and the recently described variation in the prothrombin gene. Most of the inherited abnormalities recognized to date are associated with venous thromboembolism (VTE) rather than arterial thrombosis. Approximately half of VTE episodes in patients with inherited thrombophilias occur in relation to events that are generally recognized as predisposing states, such as surgery, pregnancy, and immobilization. In this review, the risks of VTE associated with inherited risk factors are discussed, and guidelines for the diagnosis and management are presented.
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PMID:Inherited thrombophilic states. 984 Jun 87

The identified main causes of inherited thrombophilia are deficiencies of antithrombin (AT), protein C, or protein S, resistance to activated protein C associated with Factor V Leiden mutation, mutant factor II, and inherited hyperhomocysteinemia. For women from symptomatic families, these defects may be associated with an increased risk of venous thrombosis during pregnancy and/or recurrent fetal loss. Inherited thrombophilia is common and appears to be a multigenic disorder. The thrombotic risk seems to be greatest for women who have AT deficiency or more than one thrombophilic defect. The abnormalities that are now recognized are only part of the genetic predisposition to thrombosis. When assessing thrombotic risk during pregnancy, acquired risk factors as well as genetic predisposition should be considered. Increasing age, obesity, immobility, and delivery by cesarean section are major acquired risk factors. Pregnancy should be planned as far as possible, and each patient should be managed individually. During pregnancy, heparin is the anticoagulant of choice, and treatment with warfarin should be avoided because of risks for the fetus. When patients receive long-term treatment with warfarin, pregnancy should be avoided or planned, and warfarin should be discontinued before conception or as soon as pregnancy is confirmed and before 6-weeks' gestation. For women who have AT deficiency, the incidence of thrombosis during pregnancy is between 20 and 40%. Adjusted-dose heparin throughout pregnancy is recommended, followed by warfarin for at least 3 months postpartum. For patients who have Factor V Leiden, mutant factor II, or a deficiency of protein C or protein S, treatment can be based on personal and family history. Thromboprophylaxis during late pregnancy and postpartum should be considered. Fetal loss may be increased for women with inherited thrombophilia. The risk appears to be greatest for women with AT deficiency and women with more than one thrombophilic defect. For women with recurrent fetal death and inherited thrombophilia, a number of case reports claim that prophylaxis with heparin during pregnancy has resulted in successful pregnancy.
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PMID:Inherited thrombophilia and pregnancy: the obstetric perspective. 984 Jun 92

Inherited thrombophilia due to activated protein C resistance is now recognized as one of the major genetic risk factors in the development of venous thromboembolic disease. Activated protein C resistance is secondary to a point mutation in the factor V gene, factor V Leiden. The high prevalence of this mutation in the general population, mainly in Caucasians of European descent, is a major contributing factor to the high incidence of venous thromboembolic disease in the United States, affecting one in 1000 individuals annually. Heterozygosity and homozygosity for factor V Leiden increase the risk for thrombosis 5- to 10-fold and 50- to 100-fold, respectively, compared with genotypically normal individuals. Factor V Leiden is more common than all other known genetic risk factors for thrombosis, and its presence results in a compounded risk in patients with simultaneous inherited abnormalities such as protein C, protein S, antithrombin III deficiencies, hyperhomocysteinemia, and/or acquired risk factors. Therefore, detection of activated protein C resistance and genotyping for factor V Leiden are important for establishing risk for thrombosis and ultimately for patient management.
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PMID:Inherited Thrombophilia due to Factor V Leiden Mutation. 1009 58

Recurrent venous thrombotic and thromboembolic disease, once thought to be an uncommon entity, is increasingly being recognized. Etiologies of recurrent deep venous thrombosis usually include elements of Virchow's triad. Venous stasis (e.g., immobilization, congestive heart failure, acute myocardial infarction, obesity), hypercoagulability (e.g., malignancy, inflammatory bowel disease, hyperhomocysteinemia, protein C resistance, antithrombin III, protein C or S deficiency) and endothelial trauma (e.g., surgical trauma, venous trauma, in-dwelling venous instrumentation) are risk factors. Diagnosis is dependent on objective testing, including venography duplex Doppler (color) ultrasonography and impedance plethysmography. Treatment is usually started with heparin or low-molecular-weight heparin and advanced to warfarin (adjusted to international normalized ratio). Prophylaxis may continue using low-molecular-weight heparin, warfarin, venacaval interruption (Greenfield filter), or concomitant use of the platelet-active agent indobufen and graduated compression stockings.
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PMID:Clinical therapeutic conference: recurrent venous thrombotic and thromboembolic disease. 1009 38


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