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)

We studied both inherited and acquired activated protein C (APC) resistance in a group of 22 patients with primary antiphospholipid syndrome (APS). The APC resistance genotype was assessed using a PCR-based analysis for the factor V R506Q (Leiden) mutation. One patient with primary APS was found to be heterozygous for the factor V Leiden mutation. He and other family members were affected by severe thrombophilia and had a familial form of primary APS. The APC resistance phenotype was assessed by measuring the prolongation of the activated partial thromboplastin clotting time in response to APC. It was found in five out of six patients with APS, in one of them transiently. We have found that the APC resistance phenotype is more frequent than the genotype in primary APS. It would seem that patients with thrombophilia should be investigated for APC resistance even if found to have antiphospholipid antibodies and/or lupus anticoagulants.
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PMID:Activated protein C resistance phenotype and genotype in patients with primary antiphospholipid syndrome. 873 42

A point mutation in the factor V gene (factor V Leiden) is the most common cause of familial thrombophilia. Patients with factor V Leiden have an increased risk of thrombosis, particularly those homozygous for the mutation. However, the phenotype in individuals with the mutation is variable, suggesting that other factors influence thrombotic risk. We describe for the first time a family in which two independent defects in factor V co-exist: heterozygosity for factor V Leiden and factor V deficiency. Compound heterozygosity for these two defects results in a phenotype similar to a homozygous factor V Leiden state with profound resistance to APC and recurrent thrombosis.
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PMID:Recurrent thrombosis due to compound heterozygosity for factor V Leiden and factor V deficiency. 873 45

Activated protein C (APC) resistance is a common risk factor for venous thromboembolism and is associated with the replacement of Arg 506 by Gln in the factor V gene (factor V Leiden). We investigated the risk of recurrence of venous thromboembolism in APC resistant patients heterozygous for FV Leiden and compared these patient groups with a group of patients, who had a history of venous thromboembolism, but had neither APC resistance nor the FV Leiden mutation. APC resistance was determined in frozen blood samples from patients with a history of venous thromboembolism, who were not receiving oral anticoagulant (OAC) treatment. The plasma samples were collected between 1984 and 1991. Twenty-one patients in whom APC resistance was found in the stored plasma samples were reinvestigated in 1994 (5 males, 16 females, median [m] age 49 years, range 21-71 years). Twenty-one sex and age matched patients with venous thromboembolism (5 males, 16 females, age m = 50 years, range 25-73 years) investigated during the same time period who had a normal APC resistance test served as a control group. Patients with APC resistance as well as controls were reinvestigated for the presence of FV Leiden by genetic analysis in 1994. Of the 21 APC resistant patients, 5 were homozygous and 16 heterozygous for FV Leiden. Before the study entry homozygous patients had a significantly higher recurrence rate (5/5 patients) compared to the control group in heterozygous patients (9/16) and controls (9/21) the recurrence rate was not significantly different. The total observation time was 21 years in patients with homozygous FV Leiden, 83 years in patients with heterozygous FV Leiden and 108 years in controls, excluding the time when patients were on OAC treatment. During the observation time the recurrence rate was highest in patients with homozygous FV Leiden (9.5% per patient per year), but was similar in patients with heterozygous FV Leiden (4.8% per patient per year) and controls (5% per patient per year). Two of five (40%) homozygous patients, 4/16 (25%) heterozygous and 5/21 (24%) controls had a least one recurrent event during the observation period. The probability for development of thrombosis in the Kaplan-Meyer-Plot analysis was not different between the three groups. Bearing limitations of our study in mind (retrospective design, relatively small patient number) we conclude that the risk of recurrence after a thromboembolic event is not higher in patients with heterozygous FV Leiden than in patients without this mutation. Thus, it appears that the identification of heterozygous FV Leiden mutation is not an indication for long-term OAC treatment. Also, long-term OAC treatment cannot generally be recommended for homozygous patients with a single thromboembolic event. More definitive conclusions will require larger prospective studies.
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PMID:Probability of recurrence of thrombosis in patients with and without factor V Leiden. 895 Jul 97

Patients with severe meningococcal infection are characterized by extensive microvascular thrombosis, consumption coagulopathy and secondary hemorrhages. The contribution of the inherited prethrombotic disorders to the severity of the disease course is not established yet. Here, we report on the levels of protein C, protein S, antithrombin and the presence of the factor V Leiden mutation (R506Q) in 50 patients with meningococcal disease, as determined 6 to 58 months after hospital discharge. In addition, we recalled the parents of 16 deceased patients to screen for the mutation in factor V, an abnormality which results in resistance to activated protein C. Among the patients, the prevalence of the genetic risk factors for thrombosis was not higher than expected on the basis of their prevalence in the general population. Moreover, the prevalence of the factor V Leiden mutation was not increased among the parents of the deceased patients. The individual plasma levels of protein C, protein S, and antithrombin did not differ between the patients with or without severe purpura. The present data constitute circumstantial evidence that primary defects in the natural anticoagulant systems do not play a major role in the severity of the disease course. Screening of patients with infectious purpura for inherited thrombotic risk factors is therefore not indicated.
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PMID:Inherited prethrombotic disorders and infectious purpura. 882 83

Although there are numerous risk factors for venous thromboembolic disease, the term 'thrombophilia' refers only to those familial or acquired disorders of the haemostatic system that result in an increased risk of thrombosis. The inherited thrombophilias include antithrombin III deficiency, resistance to activated protein C (factor V Leiden), protein C and protein S deficiencies as well as some rare forms of dysfibrinogenaemia. It is possible that other inherited conditions might also predispose to thrombosis. In contrast, when using the above definition, the antiphospholipid syndrome is the only genuine acquired thrombophilic state. Patients who have thromboembolic disease at a young age with no provoking event or who have a positive family history or whose thrombosis involves an unusual site should be investigated for thrombophilia. The management of a patient identified as having a laboratory abnormality associated with thrombophilia will depend on a variety of factors such as the patient's individual and family thrombotic history, the site of the thrombosis and the presence of other prothrombotic risk factors. The use of prophylactic anticoagulation during pregnancy and the puerperium requires particularly careful consideration in thrombophilic women. As more becomes known about the thrombophilias it will become possible to formulate more exact guidelines as to the management of these conditions.
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PMID:Guidelines for the management of thrombophilia. Department of Haematology, The Royal London Hospital, Whitechapel, London, UK. 887 58

Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.
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PMID:APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method. 887 45

We describe the first case of Budd-Chiari syndrome due to homozygosity for factor V Leiden resulting in resistance to activated protein C. This is now recognized as the most common procoagulant disorder, and may account for many cases of Budd-Chiari syndrome previously though to be idiopathic or due to a latent myeloproliferative disorder. A further unique feature of this case is that the patient required orthotopic liver transplantation following failure of portacaval shunting and progressive hepatic necrosis. We demonstrated that liver transplantation resulted in correction of the serum coagulation abnormality; however, it is unlikely to have cured the disorder as platelet factor V would still be of the Leiden phenotype.
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PMID:Acute Budd-Chiari syndrome treated by liver transplantation in a woman homozygous for factor V Leiden. 888 63

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. For many years, stasis in the deep veins of the legs has been recognized as being a necessary but not a sufficient cause of thrombosis. The recent demonstration of the high prevalence of a mutation at Arg506 in the factor V gene ('factor V Leiden') in patients presenting with VTE has emphasized the protective role of activated protein C in neutralizing thrombin, and has highlighted the importance of genetic factors in the pathogenesis of venous thrombosis. For many if not most patients, the prothrombotic stimulus of a surgical operation with the accompanying stasis may be a sufficient cause for VTE if endogenous anticoagulant mechanisms are impaired. In populations with a high prevalence of the FV:Q506 allele there is now a strong case for screening individuals for the mutant gene if they have a personal or family history of VTE, especially before surgery, during pregnancy or before prescribing oral contraceptives.
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PMID:Venous thrombosis revisited. 889 45

APC resistance is a common and strong hereditary risk factor for venous thrombosis. This plasma abnormality appears to be almost always caused by the same defect in the coagulation factor V gene (a G --> A transition at nucleotide 1691 leading to replacement of 506 Arg by Gln; factor V Leiden). Therefore, it is possible to consider a simple and specific genetic test as an alternative to a plasma APC resistance test that is compromised by treatment and other factors. We have investigated whether a new amplification procedure, NASBA, together with the detection procedure ELGA would provide a simple protocol for the nucleotide specific detection of the factor V mutation.
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PMID:Use of the direct RNA amplification technique NASBA to detect factor V Leiden, a point mutation associated with APC resistance. 889 56

Budd-Chiari syndrome during pregnancy has rarely been reported. This report presents a case of acute hepatic failure in a 20-year-old pregnant woman attributable to Budd-Chiari syndrome with underlying resistance to activated protein C caused by factor V Leiden mutation. The patient delivered a healthy girl by cesarean section in the 31st week of pregnancy. Acute hepatic failure in the 6th week postpartum was successfully treated by emergency liver transplantation, and the patient and her child were doing well at 8-month follow-up. Liver transplantation was lifesaving; normal factor V production by the transplant corrected the underlying coagulopathy. In this patient, latent thrombophilia attributable to activated protein C resistance was apparently aggravated by the hypercoagulable state of pregnancy leading to acute Budd-Chiari syndrome. Activated protein C resistance should be sought as an etiologic factor in patients with Budd-Chiari syndrome.
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PMID:Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation. 894 48


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