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)

Hemostasis is a highly controlled system of associated biophysical and biochemical events requiring a number of molecular and cellular interactions, among which molecular assembly at surfaces is an obligatory mechanism. The exposure of flowing blood to subendothelial components results in platelet adhesion, activation, and aggregation with simultaneous exposure of negatively charged phospholipids, which serves as a template for the formation of enzyme-cofactor-substrate complexes. The locally formed proteases activate surface-bound zymogens in a sequence culminating in the formation of thrombin. Fibrinogen is transformed into fibrin by thrombin, which may also activate protein C on phospholipid membranes when bound to TM. Activated protein C is a potent anticoagulant that inactivates coagulation-activated cofactors Va and VIIIa. During this process, proteins bound to the phospholipid surfaces may adopt new configurations and expose neoepitopes, which may elicit an immunologic response giving rise to the generation of antiphospholipid antibodies. These antibodies may then interfere with the procoagulant or anticoagulant activities of the target protein-phospholipid complexes. The apolipoprotein beta 2GPI and prothrombin are the most frequently found cofactors for antiphospholipid antibodies. Components of the protein C pathway have also been identified as cofactors. The pathophysiologic effects of antiphospholipid antibodies on the thrombotic accidents observed in patients with the antiphospholipid syndrome have not been established yet.
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PMID:Antiphospholipid antibodies and the coagulation cascade. 1153 61

Sneddon syndrome is characterized by livedo reticularis and multiple cerebral infarctions. Skin and central nervous system symptoms usually have a synchronous onset and at times initial symptoms affect one of them, the other lagging several years behind. We here report a patient with Sneddon syndrome who developed multiple cerebral infarctions more than 10 years after the onset of livedo reticularis. While the neurological symptoms were apparent, the patient did not display active skin manifestations. Laboratory findings excluded collagen diseases, antiphospholipid antibody syndrome, and inherited quantitative deficiency of protein C, protein S and antithrombin III. Abnormal findings included extremely elevated levels of beta-thromboglobulin and platelet factor-4 in the blood, although these acute phase markers of thrombosis were examined several years after the onset of cerebral infarctions. Platelet activation may have caused Sneddon syndrome in the present case.
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PMID:Sneddon syndrome with multiple cerebral infarctions 12 years after the onset of livedo vasculitis: a possible involvement of platelet activation. 1160 94

We present the case of a 42-year-old female patient with the diagnoses of autoimmune hepatitis type I and autoimmune thyroiditis. Furthermore this patient had an unusual combination of coagulation disorders with homozygous Factor V Leiden mutation (APC resistance) and presence of antiphospholipid antibodies, leading to deep vein thromboses and miscarriages. Only few cases with the combination of autoimmune hepatitis and antiphospholipid antibodies have been described and almost all of them had become symptomatic with the antiphospholipid syndrome. As both autoimmune phenomenons furthermore share similar HLA-patterns, their coincidence is probably not as uncommon as the limited number of case reports suggests. Therefore attention in patients with autoimmune hepatitis should be focused on thrombophilia.
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PMID:Autoimmune hepatitis associated with coagulation disorders and immunethyreopathy. 1160 52

We report the case of a female patient who had severe thrombotic complications in peripheral (V. jugularis, subclavia, brachialis, poplitea) and visceral (portal and splenic) veins 4 years after the first diagnosis of severe ulcerative pancolitis. A thrombolysis therapy for subclavian and jugular vein thrombosis was performed without complication, but she soon developed acute thrombosis of the hepatic veins (acute Budd-Chiari syndrome). She quickly recovered after liver transplantation and now - 6 years later - she lives a normal life with continuous anticoagulation and medical therapy of the colitis.3 possible causes for the severe coagulation defect in this patient can be supposed: Thrombocytosis, protein C deficiency and an antiphospholipid antibody syndrome.
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PMID:Acute Budd-Chiari syndrome, portal and splenic vein thrombosis in a patient with ulcerative colitis associated with antiphospholipid antibodies and protein C deficiency. 1160 54

Venous thrombosis, whose main clinical presentations include deep vein thrombosis and pulmonary embolism, represents a major health problem worldwide. Numerous conditions are known to predispose to venous thrombosis and these conditions are commonly referred to as risk indicators or risk factors. Generally accepted or "classically" acquired risk factors for venous thromboembolism include advanced age, prolonged immobilisation, surgery, fractures, use of oral contraceptives and hormone replacement therapy, pregnancy, puerperium, cancer and antiphospholipid syndrome. In addition to these well-established risk factors for venous thrombosis, several lines of evidence that have emerged over the past few decades indicate a role of novel genetic risk factors, mainly related to the haemostatic system, in influencing thrombotic risk. The most significant breakthrough has been the confirmation of the concept that inherited hypercoagulable conditions are present in a large proportion of patients with venous thromboembolic disease. These include mutations in the genes that encode antithrombin, protein C and protein S, and the factor V Leiden and factor II G20210 A mutations. Moreover, plasmatic risk indicators, such as hyperhomocysteinemia and elevated concentrations of factors II, VIII, IX, XI and fibrinogen, have also been documented. This extensive list of genetic and acquired factors serves to illustrate that a single cause of venous thrombosis does not exist and that this condition should be considered as a complex or multifactorial trait. Complex traits can be understood by assuming an interaction between different mutations in candidate susceptibility genes. The risk that is associated with each genetic defect may be relatively low in isolation but the simultaneous presence of several mutations may dramatically increase disease susceptibility. Moreover, environmental factors may interact with one or more genetic variations to add further to the risk. The analysis of genetic risk factors and plasmatic factors, together with private life style and environmental factors, has contributed significantly to our understanding of the genetic predisposition to venous thrombosis.
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PMID:Genetic risk factors of venous thrombosis. 1170 18

The family of autoantibodies known as antiphospholipid antibodies (aPL) and the lupus anticoagulant (LA) are associated with a spectrum of clinical manifestations including life-threatening thrombosis. While our current knowledge of thrombosis is imperfect and the mere presence of aPL is imprecisely associated with clinical events, our knowledge in this area has greatly expanded in recent years. It is clear that high levels of IgG aPL are associated with an increased risk of thrombosis. In 1990, investigators demonstrated that some aPL are directed against the beta2-Glycoprotein I (beta2-GPI) 50 kDa subunit and reported that these showed concordance with risk of clotting in certain groups of patients. Studies have also demonstrated that aPL reacted with antigens other than beta2-GPI, namely prothrombin, annexin V, protein S, protein C and high molecular weight kininogen. We review the clinical features of the antiphospholipid syndrome (APS), including vascular occlusion, pregnancy loss, thrombocytopenia and catastrophic APS. We also review the role of antibodies in the pathogenesis of APS as well as the spectrum of autoantibodies that have been found in APS.
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PMID:Antiphospholipid antibodies in systemic lupus erythematosus and the antiphospholipid syndrome. 1172 83

Painful bilateral ophthalmoparesis, marked proptosis, increased intraocular pressure, and blindness developed in a 29-year-old woman with protein C deficiency and catastrophic antiphospholipid syndrome. Magnetic resonance imaging of the orbits showed bilateral proptosis, globe tenting, and tethering of the optic nerves consistent with an orbital ischemic syndrome. Despite aggressive therapy for antiphospholipid syndrome, the patient died. The autopsy showed necrosis of orbital tissues. This is the first report of orbital ischemic syndrome from protein C deficiency and antiphospholipid syndrome.
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PMID:Catastrophic antiphospholipid antibody syndrome manifesting as an orbital ischemic syndrome. 1175 55

Object of the study are women with a history of unexplained recurrent embryo, fetal and early neonatal death, severe preeclampsia, fetal growth retardation, abruptio placentae, puerperal thromboses. Quite often placental insufficiency is linked to abnormal vascular system and hemostatic disturbancies. In about 65% of the women with a complicated and in 18% of the women with a normal pregnancy are observed different genetic anomalies that lead to a hypercoagulative state. A major place is taken by the Leiden mutation of hemostasis factor V, by protein C and protein S deficiency, etc. Another disease that leads to arterial and venous thromboses and is most often linked to recurrent miscarriage is the antiphospholipid syndrome. Many authors confirm the findings of large placental infarctions and thromboses in women who are positive for antophospholipid antibodies.
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PMID:[Frequency of antiphospholipid antibodies and Leiden mutation of hemostasis Factor V in unexplained recurrent fetal and embryo loss]. 1178 58

Venous thromboembolism is a multifactorial disease that is defined by multiple interactions between genetic and environmental components. Inherited thrombophilia may result in a hypercoagulable state that causes an increased tendency to thrombosis. We assessed the prevalence of factor V Leiden, factor II 20210A, antithrombin III, protein C and protein S deficiency, and the presence of antiphospholipid syndrome among 325 thrombosis patients from the East Bohemian region with a first episode of thrombosis under the age of 45 years. The average age of the first thrombotic event was 34 years (age range, 14-45 years). These data are not known yet from this part of the Czech Republic. Factor V Leiden was found in 40%, factor II 20210A in 6%, antithrombin III deficiency in 4%, protein C deficiency in 6%, and protein S deficiency in 11% in this cohort. Lupus anticoagulant was detected in 8% and anticardiolipin antibodies in 6%. Our results confirm the usefulness of thrombophilia work-up in patients with venous thrombosis before the age of 45 years in our region. The diagnosis of inherited thrombophilia is important for further management of these patients.
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PMID:Prevalence of inherited thrombophilia in young thrombosis patients from the East Bohemian region. 1219 10

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.
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PMID:Prothrombotic States that Predispose to Stroke. 1235 68


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