1. Resistance To Activated Protein C activated protein c resistance Molecular mechanisms based on studies using purified Gln506factor V. Blood 1995; 85 3405-3411. http://www.jr2.ox.ac.uk/bandolier/bandopubs/keeling.html

@import "../styles/advanced.css"; Resistance to activated protein C due to Factor V R506Q (Factor V Leiden) David Keeling BSc MD MRCP MRCPath Consultant Haematologist Oxford Haemophilia Centre, Churchill Hospital, Oxford. The Discovery of Resistance to Activated Protein C and Identification of the Mechanism. The phenomenon of resistance to activated protein C (APC) was discovered only three years ago. Dahlback and colleagues identified a middle aged man with a personal and a family history of thrombosis whose APTT did not show the expected prolongation when exogenous APC was added to his plasma [1]. The same phenomenon was found in several of the patient's relatives. The mechanism was unknown but inheritance of a deficiency of a cofactor for APC was hypothesised. This proved not to be the case and one year later the molecular defect was identified as a point mutation in factor V (FV) [2]. The mutation was a G to A substitution at nucleotide position 1,691. This results in the arginine at position 506 (coding triplet CGA) being replaced by a glutamine (coding triplet CAA). Using the single letter amino-acid code the mutant FV can therefore be written as FV R506Q but is more often referred to as FV Leiden (Figure 1). Figure 1. The G to A point mutation results in the arginine at the protein C cleavage site being replaced by glutamine.

2. Activated Protein C Resistance January 2001. activated protein c resistance. Andrea Cortese Hassett, Ph.D The phenomenon of activated protein c resistance (APCr) was first reported by Dahlback (1) et al http://www.itxm.org/TMU2001/tmu1-2001.htm

January 2001 ACTIVATED PROTEIN C RESISTANCE Andrea Cortese Hassett, Ph.D. Franklin A. Bontempo, M.D. INTRODUCTION The phenomenon of activated protein C resistance (APCr) was first reported by Dahlback (1) et al. in 1993 and refers to the ability to mount an effective anticoagulant response. Clinically this results in an increased risk of thrombosis. Most cases of APC resistance are associated with a single point mutation in the factor V gene (Leiden mutation), which results in the substitution of arginine at position 506 by glutamine. Cleavage of this site by APC is necessary for exposure of the two additional cleavage sites needed for inactivation. The rate of inactivation of factor V Leiden (FVL) is therefore slower than that of normal factor V. In vivo this manifests as an 8 fold increased risk of thrombosis in heterozygotes and a 50 to 100 fold increased risk of thrombosis in homozygotes (2,3). LABORATORY METHODOLOGY The presence of the FVL allele is the major cause of APCr and a well-documented risk factor for venous thrombosis. APC resistance testing is performed on citrated plasma (blue tops) preferably away from the time of the acute event, when the patient is not on treatment with anticoagulants. The first generation, original assay consists of a standard APTT test performed in the absence and presence of commercially available activated protein C.

3. Template For Redirect Center for Disease Control's page discussing the background of this disorder including study results, testing, and complications. http://www.cdc.gov/genetics/info/reports/research/protein_C.html

If there is a problem with the automatic redirect, this page now exists at http://www.cdc.gov/genomics/info/reports/research/protein_c.html . Please reset your bookmarks.

4. November1994 - The Activated Protein C Resistance Test THE activated protein c resistance TEST. A New Test for Patients with Thrombosis The activated protein C (APC) resistance test is a recently described clotting assay that is an http://www.itxm.org/Archive/tmu11-94.htm

November, 1994 THE ACTIVATED PROTEIN C RESISTANCE TEST A New Test for Patients with Thrombosis Franklin A. Bontempo, M.D., Medical Director, Coagulation Services Andrea Cortese Hassett, Ph.D., Scientific Director, Coagulation Services Description The activated protein C (APC) resistance test is a recently described clotting assay that is an important new diagnostic tool to define a cause of hypercoagulability in patients with thrombosis. Defects affecting APC appear to be the most common cause of systemic tendency for excessive clotting. This review will summarize current information as to the incidence and significance of this abnormality. Protein C, in the presence of its cofactor thrombomodulin and thrombin, is enzymatically cleaved to its active form, Activated Protein C. APC is an important natural anticoagulant which functions by inactivating the critical coagulation factors FVa and FVIIIa. The many causes of thrombosis include both hereditary and acquired conditions. Inherited predispositions to thrombosis are perhaps the most disturbing clinically, because they affect patients at a younger age. Currently, only about 5-10% of patients with thrombosis have a definable cause of their thrombotic tendency. In the past year, however, groups working independently in California and Europe have found that failure of the APTT to prolong with the addition of activated protein C occurs in 30-40% of patients with an otherwise unknown cause of thrombosis. Further studies have shown that in 80% of these patients the cause of the APC resistance is a mutant factor V molecule, recently designated factor V Leiden, which is able to clot in the classic coagulation cascade but is resistant to activation by activated protein C.

5. Activated Protein C Resistance Information Diseases Database activated protein c resistance APC resistance Factor V Leiden disease, Disease Database Information 3 synonyms or equivalents were found. activated protein c resistance. aka/or. APC resistance http://www.diseasesdatabase.com/ddb154.htm

Diseases Database Index Sponsors Contact ... Previous Page Activated protein C resistance Information Search 3 synonyms or equivalents were found. Activated protein C resistance aka/or APC resistance aka/or Factor V Leiden disease may cause or feature (Follow link for list) may be a risk factor for (Follow link for list) may be allelic with (Follow link for list) belong(s) to the category of (Follow link for list) Activated protein C resistance: Definition(s) via UMLS Code translations and terms via UMLS Activated protein C resistance: specific sites Send Activated protein C resistance to medical search engines (JavaScript enabled browsers only) If your browser has no JavaScript you can still use these: Search using Internet medical databases Search using Internet search engines (non-specialist) We subscribe to the HONcode principles of the Health On the Net Foundation i-medicine.info - the evidence based medicine, informatics and audit portal Valid XHTML 1.0 Served 2004-06-02 08:06:37 Metadata Updated 2004-05-22

6. FVL: Activated Protein C Resistance FVL activated protein c resistance. A brief primer for those who are new to the subject of FVL is* possible to have activated protein c resistance without having FVL. http://www.naturalchildbirth.org/natural/resources/prebirth/prebirth31.htm

FVL: Activated Protein C Resistance A brief primer for those who are new to the subject of FVL: "Factor V Leiden" (FVL) is a description of a specific mutation. What that mutation causes is "Activated protein C resistance." All people with FVL have activated protein C resistance to one degree or another. However, it *is* possible to have activated protein C resistance without having FVL. There are probably certain other populations where APCR (Activated Protein C Resistance) is "acquired" through disease or environmental problems. The most common cause of APCR is FVL. Activated Protein C resistance means that when your body forms clots, those clots are more durable than they should be, which means they don't break down as easily as they ought to and they grow faster than they should. One hematologist said he thinks of it as "clot formation not slowing down the way it is supposed to." Activated Protein C is a natural anticoagulant in the blood. There are many, many other causes of thrombophilia (tendency to clot excessively), many of which are genetic. Some people have more than one

7. ACTIVATED PROTEIN C RESISTANCE ASSAY activated protein c resistance Assay. The Blood Center of Southeastern Wisconsin Hemostasis Reference Laboratory has implemented a new method for its activated protein c resistance Assay. http://www.clinlabs.org/activatedproteincresistanceassay.htm

Activated Protein C Resistance Assay The Blood Center of Southeastern Wisconsin Hemostasis Reference Laboratory has implemented a new method for its Activated Protein C Resistance Assay. BACKGROUND: Resistance to activated protein C (APCR) is the most common inherited condition associated with increased risk for thrombosis. APCR is present in 3 to 5% of asymptomatic Caucasians, and is found in about 20% of unselected patients with venous thrombosis. A single point mutation (Factor V Leiden , encoding for substitution of amino acid glutamine for arginine in the factor V protein) accounts for 95 to 99% of cases of observed activated protein C resistance. APCR/Factor V Leiden have become associated with multiple disease states including: venous thromboembolic disease, stroke in children, preeclampsia and fetal wastage. REASONS FOR REFERRAL: Evaluation of patients with hypercoagulable state, patients with a history of preeclampsia or recurrent fetal loss, and for prediction of disease risk in individuals with a positive family member. METHOD dRVVT based clotting time ratio. Patient plasma is incubated with snake venom (to activate endogenous protein C) or saline, and the dRVVT is determined for each sample. Results are expressed as the ratio of dRVVT when venom is present to the dRVVT with saline only.

8. Page Not Found Features articles about blood coagulation disorders including activated protein c resistance, von Willbrand's disease, and hypercoagulability. http://www.beckmancoulter.com/Coulter/Techpubs/coagulation/

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9. Page Not Found Discusses the thrombotic risks of this inherited disorder, also known as Factor V Leiden. http://www.beckmancoulter.com/Coulter/Techpubs/coagulation/APC.asp

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10. FamilyPractice.com - References activated protein c resistance The Most Common Risk Factor for Venous Thromboembolism of morbidity and mortality. Although activated protein c resistance (APCR) is the most http://www.familypractice.com/references/referencesframe.htm?main=/journal/2000/

11. The Role Of Activated Protein C Resistance In The Pathogenesis Of Venous Thrombo The Role of activated protein c resistance in the Pathogenesis of Venous Thrombosis. Activatedprotein C resistance in cancer patients. http://www.cdc.gov/genomics/info/reports/research/protein_c.html

Your browser does not support script Journal Publication This review was published with modifications in Am J Med Sci. 1998 Aug; 316(2): 120-128 The Role of Activated Protein C Resistance in the Pathogenesis of Venous Thrombosis by W. Craig Hooper and Bruce L. Evatt Introduction Pathophysiology APC-R and Factor V Leiden: Clinical Features FV Leiden in Women ... References Introduction Following myocardial infarction and stroke, venous thromboembolism (VTE) is the third most common cardiovascular disease in the United States. The mortality and morbidity of VTE is significant with an annual incidence of approximately 1:1000 individuals and pulmonary embolism is a leading cause of in-patient hospital deaths (1,2). It has been estimated that venous thrombosis is responsible for between 300,000-600,000 hospitalizations and up to 100,000 deaths annually (3,4). The clinical consequences of venous thrombosis such as chronic venous insufficiency with skin ulceration affects up to 500,000 individuals per year. Studies have reported that as many as 90% of patients with venous thrombosis suffer significant disabilities at 2-5 year follow-up intervals (5). The current health costs associated with VTE are significant and are expected to rise as the prevalence of VTE increases in the aging population (6,7). The purpose of this review is to briefly re-acquaint the reader with the pathobiology of the anticoagulant protein system and to review the clinical implications of APC-R.

12. Entrez PubMed The discovery of activated protein c resistance. Publication Types Review; Review, Tutorial. MeSH Terms activated protein c resistance/genetics*; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1

13. Entrez PubMed Click here to read Reactions to awareness of activated protein c resistance carriership a descriptive study of 270 women. Lindqvist http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1

14. UAB Health System | Search The ballgame isn t over, and right now we re ahead. Elvin Stanton. activated protein c resistance. activated protein c resistance. http://www.health.uab.edu/show.asp?durki=35992

15. Activated Protein C Resistance activated protein c resistance (Factor V Leiden) I. Review of Protein C and Factor V. Factor V is a proenzyme that is activated to Factor Va, whose function is to catalyze the activation of prothrombin to thrombin. can now cleave and activate Protein C. Activated Protein C in conjunction with a cofactor called Protein S inactivates http://www.medinfo.ufl.edu/year2/coag/apc.html

16. NEJM -- Resistance To Activated Protein C As A Basis For Venous Thrombosis Original Article from The New England Journal of Medicine Resistance to Activated Protein C as a Basis for Venous Thrombosis Tosetto, A. ( 1999). activated protein c resistance and Factor V Leiden Mutation Are Independent Risk Factors for http://www.nejm.org/cgi/content/abstract/330/8/517

HOME SEARCH CURRENT ISSUE PAST ISSUES ... HELP Please sign in for full text and personal services Volume 330:517-522 February 24, 1994 Number 8 Next Resistance to Activated Protein C as a Basis for Venous Thrombosis Peter J. Svensson, and Bjorn Dahlback Full Text Letters Add to Personal Archive Add to Citation Manager ... PubMed Citation ABSTRACT Background In three families with various forms of venous thrombosis, we observed an apparently inherited poor response to the anticoagulant activated protein C (APC). The condition was due to a deficiency in a previously unrecognized anticoagulant factor that functioned as a cofactor to activated protein C. Methods We conducted the present study to determine the prevalence of resistance to APC in patients with venous thrombosis. We compared 104 consecutive patients with venous thrombosis confirmed by objective tests with 130 controls. In addition, 211 members of 34 families of persons with resistance to APC were studied. The anticoagulant response to APC was measured with a modified version of the activated partial-thromboplastin time test; the

17. APCR And Factor V Leiden Mutation LexiComp, Cleveland, 2001; 327-358. activated protein c resistance and the Factor V Leiden Mutation CO004550. Related Information. http://www.mgh.harvard.edu/labmed/lab/coag/handbook/CO004550.htm

Laboratory Medicine Laboratories Coagulation Handbook APCR and Factor V Leiden Mutation Coag Test Handbook Index From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook , 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358. Activated Protein C Resistance and the Factor V Leiden Mutation [CO004550] Related Information Activated Partial Thromboplastin Time Antithrombin Hypercoagulation Panel Polymerase Chain Reaction Protein C Protein S Synonyms Activated Protein C Resistance; APC; Protein C Resistance, Activated Applies to Factor V Leiden Mutation Abstract Resistance to activated protein C (APC) is a condition which leads to a hypercoagulable state with an increased risk for venous thrombosis. The effect of exogenous APC on patient's clotting time [usually activated partial thromboplastin time (PTT)] is used to detect presence of resistance to APC (as occurs in individuals with the factor V Leiden mutation). A few laboratories might use clotting times other than the PTT. DNA-based assays can be used to directly detect the presence of the factor V Leiden mutation. Specimen Plasma (for clotting time-based screening assay) and whole blood (for DNA-based confirmatory assay)

18.  ACTIVATED PROTEIN C (APC) RESISTANCE TEST - Plasma  Interpretation activated protein c resistance is due to an inherited disorder of the (coagulation) factor V molecule, and is associated with venous http://www.rcpa.edu.au/pathman/activat3.htm

This site has been updated. Please go to www.rcpamanual.edu.au This page will be permanently removed on 30th September 2004. Please update your links. ACTIVATED PROTEIN C (APC) RESISTANCE TEST - plasma Specimen: 4.5 mL blood in 0.5 mL citrate. Method: Coagulation tests in the presence and absence of activated protein C; the clotting times are recorded. The ratio of clotting times with and without activated protein C is determined. Reference Interval: APTT-based method. Normal: Equivocal: Abnormal: Application: Investigation of tendency to venous thromboembolism: unexplained, recurrent, or with a positive family history. The test has high sensitivity and specificity and is an adequate initial test, except for patients receiving heparin or warfarin and those with other abnormalities of coagulation. In these circumstances, DNA testing for detection of the abnormal factor V gene is also available; see MOLECULAR GENETICS- INDIVIDUAL GENETIC DISORDERS – FACTOR V LEIDEN MUTATION Interpretation: see MOLECULAR GENETICS - INDIVIDUAL GENETIC DISORDERS – FACTOR V LEIDEN MUTATION . Aquired APC resistance may occur in pregnancy and in the presence of inflammation. Reference: N Engl J Med Thromb Haemostas

19. Entrez PubMed activated protein c resistancea major risk factor for thrombosis. Rosen SB, Sturk A. Chromogenix AB, Molndal, Sweden. Resistance http://respiratory-research.com/pubmed/9263726

Entrez PubMed Nucleotide Protein ... Books Search PubMed Protein Nucleotide Structure Genome Books CancerChromosomes 3D Domains Domains Gene GEO GEO DataSets HomoloGene Journals MeSH NCBI Web Site OMIM PMC PopSet SNP Taxonomy UniGene UniSTS for Limits Preview/Index History Clipboard ... Text Version Entrez PubMed Overview FAQ Tutorial New/Noteworthy ... E-Utilities PubMed Services Journals Database MeSH Database Single Citation Matcher Batch Citation Matcher ... Cubby Related Resources Order Documents NLM Gateway TOXNET Consumer Health ... PubMed Central Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links GEO Links HomoloGene Links Nucleotide Links OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links Show: Sort Author Journal Pub Date Text File Clipboard E-mail Order Eur J Clin Chem Clin Biochem. 1997 Jul;35(7):501-16. Related Articles, Links Activated protein C resistancea major risk factor for thrombosis. Rosen SB, Sturk A. Chromogenix AB, Molndal, Sweden.

20. Entrez PubMed The role of activated protein c resistance in the pathogenesis of venous thrombosis. Hooper WC, Evatt BL. Hematologic Disease Branch http://respiratory-research.com/pubmed/9704665

Entrez PubMed Nucleotide Protein ... Books Search PubMed Protein Nucleotide Structure Genome Books CancerChromosomes 3D Domains Domains Gene GEO GEO DataSets HomoloGene Journals MeSH NCBI Web Site OMIM PMC PopSet SNP Taxonomy UniGene UniSTS for Limits Preview/Index History Clipboard ... Text Version Entrez PubMed Overview FAQ Tutorial New/Noteworthy ... E-Utilities PubMed Services Journals Database MeSH Database Single Citation Matcher Batch Citation Matcher ... Cubby Related Resources Order Documents NLM Gateway TOXNET Consumer Health ... PubMed Central Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links GEO Links HomoloGene Links Nucleotide Links OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links Show: Sort Author Journal Pub Date Text File Clipboard E-mail Order Am J Med Sci. 1998 Aug;316(2):120-8. Related Articles, Links The role of activated protein C resistance in the pathogenesis of venous thrombosis. Hooper WC, Evatt BL.

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