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)

The activated protein C (APC) resistance phenotype associated with an abnormal factor V Leiden (FVL), and the G20210A prothrombin gene mutation are the most common findings in patients with venous thromboembolism (VTE). In a group of 210 patients, we compared the levels of markers of coagulation activation in carriers of FVL (71 heterozygous, 30 homozygous), G20210A prothrombin mutation (88 heterozygous) or both mutations combined (21 heterozygous), in order to assess whether these markers allow identification of a group of patients with a higher risk of thrombosis; they were also compared to normal values. A total of 143 patients had a personal history of VTE and 67 were asymptomatic. None of them had other hereditary causes of thrombophilia or an antiphospholipid syndrome. None were currently treated with either anticoagulant or hormonal treatment. Pregnant women were excluded. No significant difference between the four groups of patients could be found in the levels of F1+2, TAT and DDI. Levels were all significantly higher than the control values (p<0.05). The levels of F1+2 and TAT were similar in patients with or without a history of VTE, regardless of the type of mutation. DDI levels were significantly higher in patients with a history of VTE than in asymptomatic subjects (443+/-248 vs. 333+/-222 ng/ml, p=0.02) but with only 57% sensitivity and specificity. In conclusion, our study confirms the hypercoagulable state found in mutation carriers and points out the inability of F1+2 and TAT assays to identify a group of subjects at higher risk of thrombosis, within carriers of genetic risk factors. Although the sensitivity and specificity of DDI assay are low, high DDI concentrations tend to be associated with the risk of VTE.
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PMID:Markers of activated coagulation in patients with factor V Leiden and/or G20210A prothrombin gene mutation. 1241 82

We treated three thrombophilia-complicated pregnant women (two antiphospholipid antibody syndrome, one protein C deficiency) with low molecular weight heparin (dalteparin). All three pregnancies including one twin pregnancy ended in live births without a decrease in bone mineral density. This treatment modality was effective and safe preventing thrombosis during their pregnancies.
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PMID:Thromboprophylaxis with low molecular weight heparin in thrombophilia-complicated pregnancy. 1242 94

Anti-beta -glycoprotein I antibody (abetaGPI) has been recognized in raising the risk of cerebral ischemia in patients with antiphospholipid antibody syndrome (APS), especially by protein C (PC) axis perturbation. Although a high potential is also seen in non-APS patients, the mechanism is substantially unknown. In the present study, we examined the effect of abetaGPI on PC and antithrombin-III (AT-III) activity in non-APS patients with non-cardiac cerebral ischemia (NCCI). A total of 111 NCCI patients and 30 healthy controls were enrolled. They were free of APS manifestation, and their anticardiolipin antibody and lupus anticoagulant tests were within normal range. There were 14.4% patients found to have an abnormal increase of blood abetaGPI. The PC, AT-III, albumin, aminotransferases, creatinine, prothrombin time and activated partial thromboplastin time did not differ between our patients and controls, or patients with or without increased abetaGPI. However, a marked decrease of the PC/AT-III ratio was found in patients with increased abetaGPI. The correlation between PC and AT-III activity was highly significant in patients with an increase of abetaGPI (P = 0.001), only marginal in controls (P = 0.042), and was insignificant in patients with a normal abetaGPI (P = 0.277). The abetaGPI did not correlate to PC or AT-III activity in either patients or controls. These findings suggest that high PC/AT-III coupling may relate to NCCI in non-APS patients associated with an increase of abetaGPI. This coupling effect seems not to be caused by abetaGPI directly.
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PMID:A perturbation of antithrombin-III and protein C coupling associates with an increase of anti-beta2-glycoprotein I antibody in non-antiphospholipid antibody syndrome cerebral ischemia. 1244 9

Clinical and laboratory studies were carried out in 38 pregnant women with antiphospholipid syndrome. Increased functional activity of platelets and decreased protein-producing function of the placenta were observed starting from the early terms of gestation. These disorders were followed by the development of hypercoagulation in the plasma component of hemostasis, appearance of intravascular blood clotting markers, and inhibition of AT III and protein C. This led to the progress of disorders in the microcirculatory bed, fetoplacental insufficiency, decrease in trophoblastic beta1-glycoprotein level, chronic hypoxia, and fetal death. Infection accelerated this process. Measurements of trophoblastic beta1-glycoprotein every 2 weeks help to diagnose fetoplacental disorders, predict the course of pregnancy, and evaluate the efficiency of drug therapy.
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PMID:Trophoblastic beta1-glycoprotein and hemostasis system in pregnant women with antiphospholipid syndrome. 1253 70

Although hypercoagulable states are most often associated with venous thrombosis, arterial thromboses are reported in protein S, protein C, and antithrombin III deficiencies, factor V Leiden and prothrombin gene mutations, hyperhomocysteinemia, dysfibrinogenemia, plasminogen deficiency, sickle cell disease, and antiphospholipid antibody syndrome.
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PMID:Coagulopathies and arterial stroke. 1261 91

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear. aCLa were measured by double ELISA in patients with TAO (n = 47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n = 48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p = 0.01) or healthy individuals (2%; p < 0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p = 0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals. TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.
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PMID:Antiphospholipid antibodies in thromboangiitis obliterans. 1271 Aug 39

Inflammatory bowel diseases (IBD)--ulcerative colitis and Crohn's disease--are associated with increased risk for thrombotic complications both in the arterial and venous system. Cerebral sinus thrombosis is a rare but potentially fatal consequence of these diseases. Modern imaging methods made this uncommon complication of IBD more frequently recognized. The link between IBDs and thrombosis has been extensively studied. Inherited coagulation disorders (APC resistance, antithrombin III and protein-S deficiency), acquired diseases (antiphospholipid syndrome), and the frequent use of corticosteroids were suspected. Two cases of ulcerative colitis associated with cerebral sinus thrombosis successfully treated are reported. The connection between IBD and thrombotic complications and the therapeutic risks are discussed as well.
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PMID:[Cerebral sinus thrombosis and ulcerative colitis: two cases]. 1271 83

Protein C (PC), protein S (PS), and antithrombin III (AT-III) are vital thrombin antagonists in circulation. However, the prevalence of these natural inhibitors for cerebral ischemia is barely mentioned in the Chinese population. The prevalence of PC, PS, and AT-III deficiency in Chinese adults with cerebral ischemia is reported. The study subjects were free of antiphospholipid antibody syndrome or systemic lupus erythematosus. Cardiac, liver, and renal function were normal. An overall rate of thrombophilia was 27%. PS deficiency was the most common disorder, followed by PC with PS and PC deficiency. There was only one patient with AT-III deficiency. No gender was specific for thrombophilia. However, PS deficiency was predilected in young adults. A positive correlation between PC and AT-III was achieved in patients with a normal PC activity but not PC deficiency. There was no correlation between AT-III or PS. The odds ratios of PC and PS were 5.29 and 2.86, respectively. Accordingly, an inability for thrombin antagonization by the PC/PS axis may relate to the occurrence of cerebral ischemia in the Chinese population. AT-III seems to display a minor role only.
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PMID:The prevalence of protein C, protein S, and antithrombin III deficiency in non-APS/SLE Chinese adults with noncardiac cerebral ischemia. 1281 86

Hyperactivity of coagulation factor VIII (fVIII) marks hypercoagulation. FVIII enhances activity of factor IX and their combination activates factor X, which is of primary importance in prothrombin transformation into thrombin, on the phospholipid membrane. The activity of fVIII was studied in 28 patients (26 women, 2 men, mean age 49.6 +/- 7.8 years) with Sneddon's syndrome (SS). SS manifests clinically similarly to primary antiphospholipid syndrome (PAS). The leading of them are ischemic disorders of cerebral circulation (IDCC) and advanced livedo present in all the examinees. Hyperactivity of fVIII was registered in 21 (75%) of 28 patients. Most of thrombosis-related symptoms occurred more frequently in patients with high than normal activity of fVIII: ischemic strokes (91% vs 57%, p > 0.05), repeated strokes (71% vs 0%, p = 0.0014), transient IDCC (76% vs 57%, p > 0.05), vascular dementia (43% vs 0%, p > 0.05), ischemic heart disease (43% vs 0%, p > 0.05), thickening of heart valves according to echocardiography (91% vs 57%, p > 0.05), peripheral venous thromboses (24% vs 0%, p > 0.05). In high fVIII activity cardiolipin antibodies occurred more rarely (24% vs 43%, p > 0.05) but lupus anticoagulant was seen more often (47% vs 14%, p > 0.05). High fVIII activity was in 8 of 12 aPL-negative patients. It is demonstrated that elevated fVIII activity is an essential mechanism of thrombosis development in SS. The cause of this enhanced activity is suggested to be special aPL in interaction with which fVIII becomes insensitive to inactivation with protein C. The activity of protein C was normal in all the cases.
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PMID:[Clotting factor VIII in Sneddon syndrome]. 1459 91

Acquired abnormalities in platelets, endothelium, and their interaction occur in sepsis, immune heparin-induced thrombocytopenia (HIT), and the antiphospholipid syndrome. Although of distinct pathogeneses, these three disorders have several clinical features in common, including thrombocytopenia and the potential for life- and limb-threatening thrombotic events, ranging from microvascular (sepsis > antiphospholipid > HIT) to macrovascular (HIT > antiphospholipid > sepsis) thrombosis, both venous and arterial. In Section I, Dr. William Aird reviews basic aspects of endothelial-platelet interactions as a springboard to considering the common problem of thrombocytopenia (and its mechanism) in sepsis. The relationship between thrombocytopenia and other aspects of the host response in sepsis, including activation of coagulation/inflammation pathways and the development of organ dysfunction, is discussed. Practical issues of platelet count triggers and targeted use of activated protein C concentrates are reviewed. In Section II, Dr. Theodore Warkentin describes HIT as a clinicopathologic syndrome, i.e., the diagnosis should be based on the concurrence of an appropriate clinical picture together with detection of platelet-activating and/or platelet factor 4-dependent antibodies (usually in high levels). HIT is a profound prothrombotic state (odds ratio for thrombosis, 20-40), and the risk for thrombosis persists for a time even when heparin is stopped. Thus, pharmacologic control of thrombin (or its generation), and postponing oral anticoagulation pending substantial resolution of thrombocytopenia, is appropriate. Indeed, coumarin-associated protein C depletion during uncontrolled thrombin generation of HIT can explain limb loss (coumarin-associated venous limb gangrene) or skin necrosis syndromes in some patients. In Section III, Dr. Jacob Rand presents the most recent concepts on the mechanisms of thrombosis in the antiphospholipid syndrome, and focuses on the role of beta(2)-glycoprotein I as a major antigenic target in this condition. Diagnosis of the syndrome is often complicated because the clinical laboratory tests to identify this condition have been empirically derived. Dr. Rand addresses the practical aspects of current testing for the syndrome and current recommendations for treating patients with thrombosis and with spontaneous pregnancy losses.
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PMID:Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. 1463 96


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