21. Activated Protein C Resistance And Mutations In Factor V activated protein c resistance (APC RESISTANCE) AND MUTATIONS IN FACTOR V. MOLECULAR BASIS When thrombin (IIa) is generated, it http://www.hemex.com/testmenus/apc_resistance.htm

Home About HEMEX Whats New? VIIth PHYSICIAN TRAINING WORKSHOP ... Contacting HEMEX var site="s17hemex" 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)

22. Thrombophilia Screen Testing includes hypercoagulation study, Thrombosis study, antithrombin , protein C, protein S, activated protein c resistance, factor V leiden, factor II http://www.calgarylabservices.com/LabTests/AlphabeticalListing/T/Thrombophilia-S

Home Contact Us Useful Links Site Map ... Z List All Test Names Beginning With: A B C D ... Cytopathology Thrombophilia Screen Source Blood Mnemonic THROMB and DNATR Specimen Requirements 4 x 5 mL blue top sodium citrate tubes AND 1 x 5 mL lavender top EDTA tube  Specimen Handling PSC and RRL : Send specimens, UNSPUN at room temperature directly to DSC Special Coagulation. Must arrive within 2 hours of collection. Extra-regional : Lavender tube - ship unspun at room temperature. Blue top tubes – centrifuge at 3500 rpm for 20 minutes, aliquot plasma into 8-10 plastic tubes. Freeze and transport frozen to DSC Special Coagulation. Additional Information Testing includes hypercoagulation study, Thrombosis study, antithrombin , protein C, protein S, activated protein C resistance, factor V leiden, factor II variant lupus type inhibitor. Specimens must be accompanied with a copy of the original requistion and a Thrombosis history form. Phone Special Coagulation 770-3598/770-3599 with any questions. Testing Location Special Coagulation  Testing Frequency Alternate Name(s) Hypercoaguable screen/workup, Thrombosis study/workup

23. Specialty Laboratories ::: We Help Doctors Help Patients Print View. Factor V Leiden and activated protein c resistance A single adenineto-guanine point mutation at base 1691 in the gene coding for factor V causes http://www.specialtylabs.com/books/display.asp?id=1068

24. Activated Protein C Resistance - New Treatments, March 2, 2004 New Treatments for activated protein c resistance. Resistance to activated protein C is a congenital inherited hypercoagulable disease. http://www.medical-library.org/journals_6a/activated_protein_c.htm

Click here to view next page of this article New Treatments for Activated Protein C Resistance Resistance to activated protein C is a congenital inherited hypercoagulable disease. The problem here is that normally protein C with a co-factor of protein S controls the activity, if you will, down the coagulation pathway starting with number 11, then 12, 9, 8 and so on as the cascade moves down. This system here normally protein C co-factor S inactivates number 5 and number 8 coagulation factor proteins. They are kind of keeping a balance here to prevent ongoing conversion of soluble fibrinogen to insoluble fibrin. We see here that here is factor V and normally this undergoes degradation. But in resistance to activated protein C there is at position 506 in the factor V molecule, arginine moiety is replaced by glutamine, and this is what identifies this. The factor V gene also has an abnormality in it at position 1691. The factor V at 506, the factor V molecule, this arginine is replaced by a glutamine, it’s resistant now to the normal degradation of activated protein C, and the factor V gene here at 1691 a glutamine is replaced by an arginine. This problem is variously reported in different articles and publications to be at a frequency rate in some places of 30, 40, 50, 60% of the populations that are studied. However you and I all know that thrombosis is not in any way shape or form found in that frequency. So one must be somewhat concerned about this and the absolute direct connection that it may have. This may not always really be the answer for this situation, but of the things that you can look for today, it’s certainly going to be high on the list for an etiologic or diagnostic test that can be done. So don’t forget about this population of resistance to activated protein C. The presence of the factor V Leyden molecule, which does not undergo normal degradation as it should, by protein C with a co-factor of protein S.

25. ACTIVATED PROTEIN C RESISTANCE activated protein c resistance. TEST CODEAPRTC CPT CODE85335. SYNONYMS TEST INCLUDES LABORATORY HematologyCoagulation SPECIMEN http://healthsystem.virginia.edu/internet/labtests/clinical/a/aprtc.cfm

UVa Medical Laboratories Handbook Anatomic Pathology Clinical Pathology Site Index Search this site: ACTIVATED PROTEIN C RESISTANCE TEST CODE: APRTC CPT CODE: SYNONYMS: TEST INCLUDES: LABORATORY: Hematology-Coagulation SPECIMEN: Blue Top, 4.5 mL citrated blood MINIMUM VOLUME: Small Blue Top, 2.7 mL citrated blood AVAILABILITY: By consultation only TURNAROUND TIME: Final report pending Pathologist review. Contact laboratory at 924-8007 for STAT testing and STAT results. SPECIAL INSTRUCTIONS: REFERENCE RANGE: UVa Medical Laboratories Handbook UVa Health System PO Box 800168 Charlottesville , VA 22908 fax: 434-982-1880 For comments and suggestions about this page: calamity@virginia.edu Last Modified: 04/23/2003 of the University of Virginia About This Site

26. NEJM -- Resistance To Activated Protein C As A Basis For Venous Thrombosis 1999). activated protein c resistance and Factor V Leiden Mutation Are Independent Risk Factors for Venous Thromboembolism. Ann http://content.nejm.org/cgi/content/short/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

27. PharmGKB: Activated Protein C Resistance activated protein c resistance. Alternate Names APC Resistance; Resistance, APC. PharmGKB Primary Data. Phenotype Data Sets None. Literature Annotations. http://www.pharmgkb.org/do/serve?objId=PA446880&objCls=Disease

28. Antiphospholipid Antibodies And Activated Protein C Resistance - Chapter 3: Hype Activated protein C cleaves (divides) and inactivates coagulation factors Va and VIIIa in the V Leiden, causes factor V to be resistant to protein C and can http://www.venous-info.com/handbook/hbk03f.html

Phospholipids are fats that contain phosphorus. Antiphospholipid (APL) antibodies are acquired antibodies to phospholipid-bound protein and prothrombin. These antibodies can prolong coagulation times. APL antibodies occur in about 5% of the population, including healthy persons and are common in people with lupus erythematosus (10–30%) other connective tissue disorders, cancer, HIV, drug and possibly estrogen intake, pulmonary embolism, intravenous catheter thrombosis, or thrombosis in the liver, portal vein, kidney, or retina. A person with APL antibodies who has symptoms needs to take heparin for the acute event, then long-term warfarin. Some physicians prescribe steroids also. A person with APL antibodies who has lupus (lupus anticoagulant) and no symptoms and is having vascular reconstruction should take antiplatelet therapy such as aspirin preoperatively, heparin therapy during the operation, and warfarin postoperatively. Activated protein C cleaves (divides) and inactivates coagulation factors Va and VIIIa in the presence of protein S. This system allows blood to clot while maintaining fluidity. A genetic change in factor V, called

29. Turkish Journal Of Haematology The Prevalence of activated protein c resistance and FV Leiden in Healthy Population of Edirne, Turkey. Mutlu VURKUN * , Özden VURAL http://tjh.dergisi.org/text.php3?id=207

30. Activated Protein C Resistance activated protein c resistance. The Most Common Risk Factor for Venous Thromboembolism. from Journal of the American Board of Family Practice http://www.medscape.com/viewarticle/405768

31. Activated Protein C Resistance medscape.com/viewarticle/405768. activated protein c resistance. The Most Common Risk Factor for Venous Thromboembolism. Dawn R. Sheppard http://www.medscape.com/viewarticle/405768_print

32. ACTIVATED PROTEIN C RESISTANCE activated protein c resistance (0890240). Synonyms APCR. CPT 4 Code 85307. Test Order Mnemonic APCR. Applies To A screening assay http://www.utmb.edu/lsg/LabSurvivalGuide/hem/ACTIVATEDproteinC_Resistance.htm

A B C D ... LSG Home ACTIVATED PROTEIN C RESISTANCE (089-0240) Synonyms: APCR CPT 4 Code Test Order Mnemonic: APCR Applies To: A screening assay for the detection of activated protein C resistance (APCR) in patients with a history of recurrent venous thrombosis. Most patients with a positive APCR screening assay have a specific mutation in the coagulant factor V gene (Factor V Leiden mutation). Test Includes: APCV Ratio; Interpretation of result. Lab: Hematopathology Request Form: Hematology A Collection: Patient should be at rest for 10-20 minutes prior to collection. Standard venipuncture collection for Coagulation specimens. Discard 1st ml of blood or collect other tubes (EDTA, Serum-separator, etc.) prior to collecting sample in 3.2% citrate (light blue-top) tube. Storage Instructions: Viable for 4 hours at room temperature. If time from draw to delivery is to be greater than 4 hours, centrifuge the sample, separate the plasma from cells, and snap freeze (-70°C) the plasma. Snap frozen plasma is viable for 6 months. Special Instructions: Prior to ordering this test, verify that the APTT is in the normal range

33. Activated Protein C Resistance, The Factor V Leiden Mutation, And A Laboratory T 126, No. 5, pp. 577–582. activated protein c resistance, the Factor V Leiden Mutation, and a Laboratory Testing Algorithm. 3. activated protein c resistance. http://arpa.allenpress.com/arpaonline/?request=get-document&doi=10.1043/0003-998

34. Activated Protein C Resistance 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. Google, WWW Medical.WebEnds.com. activated protein c resistance. APC Resistance; Resistance, APC. http://medical.webends.com/kw/Activated Protein C Resistance

Medical.WebEnds.com - Medical Terminology Dictionary A B C D ... Z WWW Medical.WebEnds.com Activated Protein C Resistance APC Resistance; Resistance, APC A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form o f Factor V ( Factor V a) is more slowly degraded by activated protein C Factor V Leiden mutation (R506Q) is the most common cause of APC resistance. Google links Processing time was 0.35738587379456 seconds.

35. Blackwell Synergy - Cookie Absent activated protein c resistance in anterior ischaemic optic neuropathy. Istvan Czuriga. Gyorgy Pfliegler. Key words activated protein c resistance. Leiden mutation. http://www.blackwell-synergy.com/links/doi/10.1111/j.1600-0420.2004.00226.x/enha

Home An Error Occurred Setting Your User Cookie A cookie is a small amount of information that a web site copies onto your hard drive. Synergy uses cookies to improve performance by remembering that you are logged in when you go from page to page. If the cookie cannot be set correctly, then Synergy cannot determine whether you are logged in and a new session will be created for each page you visit. This slows the system down. Therefore, you must accept the Synergy cookie to use the system. What Gets Stored in a Cookie? Synergy only stores a session ID in the cookie, no other information is captured. In general, only the information that you provide, or the choices you make while visiting a web site, can be stored in a cookie. For example, the site cannot determine your email name unless you choose to type it. Allowing a web site to create a cookie does not give that or any other site access to the rest of your computer, and only the site that created the cookie can read it. Please read our for more information about data collected on this site.

36. Blackwell Synergy - Cookie Absent activated protein c resistance in anterior ischaemic optic neuropathy. activated protein c resistance was found in six of 25 patients (24%) in the study group. http://www.blackwell-synergy.com/links/doi/10.1111/j.1600-0420.2004.00226.x/full

Home An Error Occurred Setting Your User Cookie A cookie is a small amount of information that a web site copies onto your hard drive. Synergy uses cookies to improve performance by remembering that you are logged in when you go from page to page. If the cookie cannot be set correctly, then Synergy cannot determine whether you are logged in and a new session will be created for each page you visit. This slows the system down. Therefore, you must accept the Synergy cookie to use the system. What Gets Stored in a Cookie? Synergy only stores a session ID in the cookie, no other information is captured. In general, only the information that you provide, or the choices you make while visiting a web site, can be stored in a cookie. For example, the site cannot determine your email name unless you choose to type it. Allowing a web site to create a cookie does not give that or any other site access to the rest of your computer, and only the site that created the cookie can read it. Please read our for more information about data collected on this site.

37. 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 thrombosis in 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

38. Contents Prevalence of activated protein c resistance among women with recurrent miscarriage. Key words recurrent miscarriage, activated protein c resistance. Summary. http://medicina.kmu.lt/0403/0403-05e.htm

Medicina 2004; 40 (3) 225-231 Prevalence of activated protein C resistance among women with recurrent miscarriage , Said Makari Clinic of Obstetrics and Gynecology, Kaunas University of Medicine, Department of Physics, Mathematics and Biophysics, Institute of Cardiology, Kaunas University of Medicine, Lithuania Key words: recurrent miscarriage, activated protein C resistance. Summary. Since 1996 activated protein C resistance is closely associated with various obstetric pathologies. The most widely discussed is that of secondary infertility due to recurrent miscarriage. However, there is still widespread discussion about the role of activated protein C resistance in this and other obstetric pathologies. Aim. To investigate whether the activated protein C resistance is a cause of early recurrent miscarriage. Material and methods. A study was designed as a case-control study. Two study groups were formed. Group I included women who have experienced 2 or more miscarriages (61 patients), and Group II included women who have experienced 3 or more miscarriages (33 patients). We investigated the prevalence and compared it in the control and both study groups. Conclusion. Activated protein C resistance might be a factor behind spontaneous recurrent miscarriage. There was no statistically significant difference between women who had suffered from 2 or 3 spontaneous abortions.

39. Factor V Leiden / Thrombophilia Support Page - Recently Diagnosed - Activated Pr Recently Diagnosed Factor V Leiden, activated protein c resistance and Protein C Deficiency. by Michael Wosnick As everyone on http://www.fvleiden.org/rec_diagnosed/explanations.html

Home Mailing List Programs Reference ... Recently Diagnosed - Factor V Leiden, Activated Protein C Resistance and Protein C Deficiency by Michael Wosnick As everyone on this list probably knows, the clotting "cascade" as they call it is very complex with multiple steps. It is not an A to B kind of thing, but rather and A to B to C to D to .... You can think of this pathway as a road through a series of points, with your ultimate destination being a blood clot at the end of the pathway. But, at each step you can think of having a traffic cop that tells you to speed up (towards clotting) or to slow down (towards not clotting). There are multiple traffic cops and multiple control points. Messing up any of these control points can lead to excess clotting (car is going too fast) or not enough clotting (car is going too slow). Factor V itself is a clotting factor, whose normal role is to help blood to clot when an appropriate trigger is present. However, like all steps in the complex clotting cascade, Factor V is subject to regulation to keep it under control so that clots don't form too easily or too quickly. If you think of normal Factor V as a car on a road, then left to its own devices, it will drive towards the formation of a blood clot. Normally, however, Factor V is not just left to its own devices, but is in fact quite controlled by one of several "traffic cops". The main traffic cop is called Activated Protein C (APC). Another helper traffic cop working with APC is Protein S. Normally, APC interacts with Protein S, and together they make a combo whose job it is to slow down the Factor V so that it does not lead to excessive clotting. To be precise, APC combines with Protein S and functions to inactivate some of the normal Factor V by clipping it into a couple of pieces, rendering the car immobile. Ergo, no clot forms.

40. Factor V Leiden / Thrombophilia Support Page - Living With Thrombophilia Factor V Leiden Prothrombin 20210 Mutation activated protein c resistance Protein C S Deficiency Antithrombin Deficiency and other clotting disorders. http://www.fvleiden.org/

Home Mailing List Programs Reference ... Search Factor V Leiden Prothrombin 20210 Mutation Activated Protein C Resistance Antithrombin Deficiency and other clotting disorders If you have comments, questions, or want to post something on this web site, please send email to Deborah Okner Smith Why am I doing this? page updated 4/11/2004 links updated 12/13/03 Factor V Leiden is the most common hereditary blood coagualtion disorder in the United States. It is present 5% of the in the Caucasian population and 1.2% of the Afro-American population. Factor V Leiden increases the risk of venous thrombosis 3-8 fold for heterozygous (one bad gene inherited) and substantially more, 30-140 fold, for homozygous (two bad gene inherited) individuals. The prothrombin 20210 mutation is the second most common inherited clotting abnormality. It is more common than protein S and C deficiency and Antithrombin deficiency combined; 2% of the general population is heterozygous. It is only a mild risk factor for clots, but together with other risk factors (such as oral contraceptives, surgery, trauma, high blood pressure, obesity, smoking, etc) or combined with other clotting disorders (like Factor V Leiden), the risk of clotting increases dramatically. Factor V Leiden can be associated with the following complications: Venous Thrombosis blood clots in veins, such as:

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