1. Whoops Discusses the thrombotic risks of this inherited disorder, also known as Factor V Leiden. http://www.beckmancoulter.com/Coulter/Techpubs/coagulation/APC.asp

var brname = ""; document.writeln(''); Whoops! We apologize for any inconvenience, however, we are unable to find the page you specified. If you are using a "bookmark" or "favorite places" which was set on or before September 10, 2001, you may need to reset it since our website has been restructured. You may encounter a link that we have missed or set incorrectly. If you wish to report this information, please feel free to send us feedback , to the attention of our Webmaster. You might also consider using our search facility to locate the information you desire. Thank you, Beckman Coulter Inc. Home Products Customer Support Resource Center ... Printing Instructions

2. 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.

3. FVL: Activated Protein C Resistance FVL activated protein c resistance A However, it *is* possible tohave activated protein c resistance without having FVL. There 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

4. November1994 - The Activated Protein C Resistance Test THE activated protein c resistance TEST. A New Test for Patients with Thrombosis 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 activated protein c resistance (Factor V Leiden). I. Review of ProteinC and Factor V Factor V is a proenzyme that is activated to http://www.medinfo.ufl.edu/year2/coag/apc.html

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. Therefore, FVa is a potent procoagulant. Protein C is a Vitamin K-dependent protease that functions as an anticoagulant by inactivating Factor Va. In intact vessels, thrombin binds thrombomodulin (an endothelial cell transmembrane protein). This binding converts thrombin from a procoaglulant to anticoagulant protease which can now cleave and activate Protein C. Activated Protein C in conjunction with a cofactor called Protein S inactivates both Factor Va and VIIIa. II. History Then in 1993 in Holland, Dahlback et al. made a significant discovery. In their experiments to determine the cause of many of these unexplained thrombotic events, they administered exogenous activated protein C (APC) to patients' plasma and then measured the aPTT . In normal healthy men, when exogenous APC was given, the aPTT was substantially prolonged. This was expected given the role of Protein C in inhibiting factors Va and VIIIa. However, when many men with history or family history of unexplained thrombosis were given APC, the aPTT was not prolonged nearly as much. With this novel finding in mind, they proposed mechanisms that could account for this APC resistance. Their hypotheses included: autoantibody against Protein C, antiphospholipid antibodies inhibiting APC function, fast-acting inhibitor of APC, and Protein S Deficiency. They excluded all of these possibilities experimentally, leaving mutation in the genes for Factors V and VIII as possible mechanisms. Through their experiments they eventually found that adding normal Factor V corrected the abnormality and actually prolonged the aPTT to expected levels. This led to studies searching for mutations in the gene for Factor V as the cause for APC resistance.

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

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.

7. Whoops Features articles about blood coagulation disorders including activated protein c resistance, von Willbrand's disease, and hypercoagulability. http://www.beckmancoulter.com/Coulter/Techpubs/coagulation/

var brname = ""; document.writeln(''); Whoops! We apologize for any inconvenience, however, we are unable to find the page you specified. If you are using a "bookmark" or "favorite places" which was set on or before September 10, 2001, you may need to reset it since our website has been restructured. You may encounter a link that we have missed or set incorrectly. If you wish to report this information, please feel free to send us feedback , to the attention of our Webmaster. You might also consider using our search facility to locate the information you desire. Thank you, Beckman Coulter Inc. Home Products Customer Support Resource Center ... Printing Instructions

8. FamilyPractice.com - References activated protein c resistance The Most Common Risk Factor for Venous Thromboembolism http://www.familypractice.com/references/referencesframe.htm?main=/journal/2000/

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

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.

10. Activated Protein C Resistance January 2001 activated protein c resistance. INTRODUCTION. The phenomenon of activatedprotein 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.

11. ACTIVATED PROTEIN C RESISTANCE ASSAY activated protein c resistance Assay The Hemostasis Reference Laboratory of The Blood Center Diagnostic Laboratories has modified the method used in the 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.

12. UPC Diagnosis Series - Disease Diagnosis -Activated Protein C Resistance - Inter Considered positive for activated protein c resistance. Confirmatory assay should be performed to determine if patient http://www.upcmd.com/dot/examples/01132/interpretation.html

UPCMD Home Disease Diagnosis Home Authors-Editors Disease information ... Controversy Search Disease Diagnosis Activated Protein C Resistance Result Interpretation Testing Summary Initial Testing Activated Protein C Resistance Confirmatory Testing Factor V Leiden Polymerase Chain Reaction Monitoring Testing No testing recommended Activated Protein C Resistance, screening assay (with dilution in factor V deficient plasma) Results reported as a ratio, no units: The ratio represents the clotting time in the presence of exogenously supplied activated protein C, divided by the clotting time in the absence of activated protein C. Each laboratory determines its own reference range, but the cut-off is usually at or near 2.0. Laboratories should choose a cut-off that maximizes sensitivity. Essentially no patients with values above the cut-off have the factor V Leiden mutation [ ref Ratios above reference range cut-off: Consistent with normal response to activated protein C No evidence for activated protein C resistance or for the factor V Leiden mutation Confirmatory assay is not necessary.

13. Activated Protein C Resistance And Mutations In Factor V Updated February 2, 2000. activated protein c resistance (APC RESISTANCE)AND MUTATIONS IN FACTOR V. MOLECULAR BASIS When thrombin http://www.hemex.com/apc_resistance.htm

Updated February 2, 2000 ACTIVATED PROTEIN C RESISTANCE (APC RESISTANCE) AND MUTATIONS IN FACTOR V MOLECULAR BASIS: When thrombin (IIa) is generated, it has both procoagulant activities and anticoagulant activities. Excess thrombin is washed downstream where it binds to thrombomodulin (TM) on endothelial cells of the vessel wall. Protein C from plasma binds to the IIa/TM complex and is cleaved to its active form, termed "activated Protein C" (APC). APC is one of the most physiologically important anticoagulants as it selectively degrades the coagulation cofactors, Va and VIIIa to limit thrombin generation, fibrin formation and blood clotting in vivo. It has been shown that APC resistance results from a mutant Factor Va molecule, termed Factor V Leiden. This molecule has a specific point mutation (Arg -> Gln ) which cannot be degraded by APC in more than 90% of all APC resistant patients2. The defective Va is able to clot as normal and clotting continues because of this resistance to inactivation by APC. Other APC cleavage sites in the Factor Va molecule are potential mutation sites. These sites include: Arg -> Gln and Arg -> Gln . The other 10% of APC resistance includes Acquired APC Resistance and these secondary sites. Recent studies have shown the occurrence of APC resistance to vary from 2 - 16% depending on the population studied. This data suggests that screening protocols for hereditary thrombotic disorders should include testing for APC resistance as an important genetic risk factor. Hypercoagulability has been explained by hereditary deficiencies of Protein C, Protein S and Antithrombin in only 9 to 21% of thrombotic cases in patients without the usual risk factors for thrombosis (i.e., cancer, recent surgery, lupus anticoagulant)

14. UPC Diagnosis Series - Disease Diagnosis -Activated Protein C Resistance - Alter First test described for activated protein c resistance ref. Many laboratories have replaced this test with the http://www.upcmd.com/dot/examples/01132/alternative.html

UPCMD Home Disease Diagnosis Home Authors-Editors Disease information ... Controversy Search Disease Diagnosis Activated Protein C Resistance Alternate Tests Activated Protein C Resistance, screening assay (without dilution into factor V deficient plasma) Normalized ratio for Activated Protein C Resistance, screening assay (with or without dilution into factor V deficient plasma) Invasive Signal Amplification Reaction Activated Protein C Resistance, screening assay (without dilution into factor V deficient plasma) [CPT-85999] Performed the same as described in Recommended Tests , except sample is not diluted beforehand. First test described for activated protein C resistance [ ref Many laboratories have replaced this test with the modified screening test that includes dilution into factor V deficient plasma. The dilution step improves assessment for the factor V Leiden mutation. Sensitivity for detecting factor V Leiden mutation is only 50-86%. The specificity is 75-98% in adults [ ref ]. There is considerable overlap between normals and heterozygotes in the 2.0 to 3.0 range of assay values [ ref Inaccurate in individuals with an abnormal baseline Partial Thromboplastin Time (PTT).

15. Activated Protein C Resistance: The Most Common Risk Factor For Venous Thromboem activated protein c resistance The Most Common Risk Factor for VenousThromboembolism. Dawn R. Sheppard, DO, General Leonard Wood http://www.familypractice.com/journal/2000/v13.n02/1302.04/art-1302.04.htm

Activated Protein C Resistance: The Most Common Risk Factor for Venous Thromboembolism Dawn R. Sheppard, DO, General Leonard Wood Army Community Hospital, Ft Leonard Wood, Mo. [J Am Board Fam Pract 13(2):111-115, 2000. © 2000 American Board of Family Practice] Abstract Background: Venous thromboembolism is a major cause of morbidity and mortality. Although activated protein C resistance (APC-R) is the most commonly recognized inherited risk factor for venous thromboembolism, little is known about its long-term implications on health. Methods: MEDLINE was searched from January 1989 through August 1999 using the key words "thromboembolism," "thrombosis," "activated protein C resistance," and "factor V Leiden." Results: One in 1000 people in the United States is affected by venous thromboembolism annually. APC-R is now understood to be responsible for up to 64% of these cases. APC-R, which occurs widely in some ethnic groups and is nearly absent in others, is due to a single point mutation in the gene for clotting factor V. As a result, inactivation of factor V by activated protein C is impaired, leading to a hypercoagulable state. This condition creates a lifelong increased risk of thrombosis and, possibly, anticoagulant therapy. Conclusion: Family physicians have a new tool for assessing risks for venous thromboembolism. Recognizing that up to 64% of patients with venous thromboembolism can have APC-R and treating this disorder with prophylactic and therapeutic anticoagulation might reduce patient morbidity and mortality from venous thromboembolism. Screening high-risk patients might now be indicated.

16. Member Sign In activated protein c resistance The Most Common Risk Factor for Venous Thromboembolismfrom Journal of the American Board of Family Practice http://www.medscape.com/viewarticle/405768

If you are having trouble logging in: In order to use Medscape, your browser must be set to accept "cookies." To find out how to adjust your browser settings, please click here Log In Username Password Forgot your password? Not a Member? Register Now for free access to: MEDLINE (Optimized for Physicians) 200+ Free CME Courses 25 Medical Specialty Sites 100+ Medical Journals Conference Coverage Daily Medical News About Medscape Help WebMD Health

17. Member Sign In Hypercoagulability Clinical Assessment and Treatment from Southern MedicalJournal. activated protein c resistance. The pathophysiologic http://www.medscape.com/viewarticle/415086_4

If you are having trouble logging in: In order to use Medscape, your browser must be set to accept "cookies." To find out how to adjust your browser settings, please click here Log In Username Password Forgot your password? Not a Member? Register Now for free access to: MEDLINE (Optimized for Physicians) 200+ Free CME Courses 25 Medical Specialty Sites 100+ Medical Journals Conference Coverage Daily Medical News About Medscape Help WebMD Health

18. ASEM V68N7: Activated Protein C Resistance As A "new" Cause Of Deep Venous Throm activated protein c resistance as a new cause of deep venous thrombosisin aviators. Emonson DL Aviat Space Environ Med 1997; 686068 Abstract. http://www.asma.org/Publication/abstract/v68n7/68-606.htm

Activated protein C resistance as a "new" cause of deep venous thrombosis in aviators Emonson DL Aviat Space Environ Med 1997; 68:606-8 Abstract Aviators are occasionally diagnosed as suffering from deep venous thrombosis (DVT). Despite the recognition of the "Economy Class Syndrome" in the 1960's, the relationship between DVT and aviation is not clear cut. A case of DVT is described in a military navigator who was also found to be a heterozygote for activated protein C resistance. This case highlights the importance of considering all components of Virchow's triad when assessing the significance and management of DVTs. Aspects of the Economy Class Syndrome and of activated protein C resistance are discussed. Information on subscribing, and on obtaining copies of an article or of an entire issue. Table of Contents for Volume 68, Number 7 of the ASEM journal. ASEM Home Page

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

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

20. RESISTANCE TO ACTIVATED PROTEIN C AS PATHOGENIC FACTOR OF VENOUS THROMBOEMBOLISM Key words activated protein c resistance A chromogenic assay for activatedprotein C resistance has been introduced by Varadi et al. (97). http://www.lfhk.cuni.cz/periodik/actamed/39_2/anchroba.htm

HomePage Back Last modified ACTA MEDICA (Hradec Kralove) 1996; 39: REVIEW ARTICLE RESISTANCE TO ACTIVATED PROTEIN C AS PATHOGENIC FACTOR OF VENOUS THROMBOEMBOLISM Ladislav Chrobak, Petr Dulicek Ist Department of Medicine Charles University, Faculty of Medicine and Faculty Hospital; (Head: prof. MUDr. J. Kvasnicka, CSc.) Department of Clinical Haematology Charles University, Faculty of Medicine and Faculty Hospital; (Head: prof. MUDr. L. Chrobak, CSc.) Summary: Key words: Activated protein C resistance Supported by Grant No IGA 3691-3 from the Ministry or Health of the Czech Republic. The APC is inhibited in plasma by two major inhibitors, protein C inhibitor (PCI) which is heparin dependent and a1 - proteinase inhibitor (historically called a1 - antitrypsin) which is heparin independent. a2 - macroglobulin also appears to play a role when large amounts of activated protein C are generated in pathologic conditions such as disseminated intravascular coagulation (60). Data from several laboratories suggest that the large majority of APC - resistant individuals is carrier of factor V mutation (1, 5, 19, 74, 84, 85, 103), but not all cases of APC - resistance are explained by the mutation (1, 4, 99, 104). Swensson et al. in 1993 (88) and 1994 (89) and several other investigators confirmed that APC - resistance is the most common genetic defect in thrombosis patients (5, 35, 43, 45, 53, 99). The prevalence of APC - resistance varied between 17 % (45) and 64 % (43).

A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z

Page 1     1-20 of 87    1  | 2  | 3  | 4  | 5  | Next 20