1 / 38

Role of laboratory testing for venous thromboembolism risk factors in guiding therapy

Risk Factors for Venous Thromboembolism. . Virchow's Triad1856. Vessel Wall TraumaThrombophilicConditions in bloodStasis. . . . venous thromboembolism: acquired risk factors. temporaryMajor traumaHip/knee replacementmajor surgeryimmobilized legAcute medical illnessCentral venou

esben
Download Presentation

Role of laboratory testing for venous thromboembolism risk factors in guiding therapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


    1. role of laboratory testing for venous thromboembolism risk factors in guiding therapy Charles Eby M.D

    2. Risk Factors for Venous Thromboembolism

    3. venous thromboembolism: acquired risk factors temporary Major trauma Hip/knee replacement major surgery immobilized leg Acute medical illness Central venous catheter Pregnancy/OCP/HRT “prolonged” travel persistent Cancer Phospholipid antibodies/Lupus Anticoagulant Previous VTE

    4. Incidence of VTE

    9. the original thrombophilia trio Antithrombin protein C protein S Inheritance: autosomal dominant, incomplete penetrance Prevalence: 1:2000-5000 1: 200-300 1: 800* VTE Prevalence: 1-3% 1-3% 1-3% relative risk 60-150 6-9 24 * Br J Haem 113: 636-41, 2001

    10. Blockbusters of the 1990’s Act. Protein C resistance >90% factor V Leiden + Arg506gln eliminates aPC cleavage site in factor Va 5% carriers, U.S. whites 2.3% carriers Hispanics 1.5% carriers U.S. blacks 20% spont.VTE are FVL + Relative risk: FVL heterozygous: 7 FVL homozygous: 80 Prothrombin G20210A 30% higher FII activity 2% carriers, U.S. whites 6% spont. VTE are PG 20210 + Relative risk: PG heterozygous: 2.8 PG homozygous: ?

    11. VTE congenital risk factors: 2003 coagulation regulation: partial deficiencies: antithrombin, protein C, protein S coagulation factors: factor V Leiden , G20210A prothrombin mutation factors XI, IX, and VIII, fibrinogen miscellaneous: dysfibrinogenemia, plasminogen deficiency,diminished fibrinolysis, hyperhomocysteinemia, TAFI, etc.

    13. Why order a thrombophilia risk factor laboratory evaluation? To provide an explanation for VTE To identify risk factors that can be modified To predict risk of VTE in asymptomatic kin To assess risk for recurrent VTE To identify risk factors for pregnancy complications

    14. Recurrence rate is minimal for transient VTE risk factors

    15. Who is likely to be at increased risk for recurrent VTE? Patients with: Weak temporary risk factors Spontaneous DVT/ PE Onset < 50 years old Recurrent events Definitive positive family history in 10 relatives

    16. What tests should be included in a thrombophilia evaluation? Antithrombin activity Protein C activity (clot or chromogenic) Protein S free antigen Factor V Leiden first aPC screen, if +, genotype to confirm Prothrombin G20210A genotype Homocysteine fasting Phospholipid antibody IgG+IgM anticardiolipin Lupus Anticoagulant

    17. Thrombophilia testing: What can go wrong? Misinterpreting temporary decreases in protein C, protein S, and antithrombin as inherited deficiencies Acute thrombosis Heparin therapy Warfarin therapy Protein S and concurrent pregnancy/OCP use Poor test precision Elevated homocysteine due to: Non-fasting Ex-vivo release from red cells

    18. protein C and antithrombin activities during acute DVT

    19. protein S function during acute DVT

    20. 2001 College of American Pathology: coagulation test proficiency Specimen: 70% NPP, 30% buffer Test range median CV% Antithrombin 46-121 66 15% Protein S total 26-61 54 16% Protein S free 32-70 49 20% Protein S act 20-86 45 21% Protein C antigen 30-78 56 19% Protein C act 34-100 58 16%

    21. Thrombophilia testing: what can go wrong? continued Activated protein C resistance (aPCr) Rarely false positive if pt. plasma is prediluted with factor V depleted plasma FVL molecular tests Remote chance of aPCr mutation at alt. site Prothrombin G20210A genetic testing is specific and sensitive

    22. Thrombophilia testing: what else can go wrong? Phospholipid antibody testing Phospholipid antibody syndrome diagnosis based on one test result. Confirm persistence Minimally cardiolipin antibodies, isolated IgA Commercial labs with long phospholipid antibody panels No gold standard method for L.A. > 2 screening tests should be performed, and + screen confirmed

    23. Do positive thrombophilia tests predict increased risk of recurrent VTE? Based on recent prospective studies Factor V Leiden (+/-) NO Prothrombin 20210 (+/-) NO Anticardiolipin IgG YES Lupus anticoagulant YES AT, PC,PS, multiple risks excluded/too rare

    24. Candidates for prolonged (12 months), to indefinite OAT One VTE and Phospholipid antibody syndrome Antithrombin deficiency Factor V Leiden homozygote? Combined inherited risk factors (FVL and PG 20210)? Protein C and S deficiencies????? 6th AACP consensus conference Chest 2001 119(suppl 1)

    25. Do global tests of hemostasis predict recurrent VTE? Fibrinolysis Euglobulin lysis time pre/post venous occlusion Thrombin generation Prothrombin fragment F1+2 Thrombin and fibrinolysis D-dimer levels

    26. Risk of VTE recurrence based on D-dimer cut-off of 250 ng/ml

    29. Testing asymptomatic kin for thrombophilia risk factors- three cases 33 white male, objectively confirmed spontaneous DVT 30 year old brother with spontaneous DVT one month earlier Their 58 year old father had spontaneous PE at 28, recurrence after stopping warfarin, on chronic OAT

    30. Thrombophilia testing: repeatedly low antithrombin activities (50-60%) both sons have two children, < 10 years old Should the 3 daughters and one son be screened for AT deficiency? If deficient, what kind of prophylaxis should be recommended?

    31. VTEs in asymptomatic carriers of AT, Protein C and S deficiencies

    33. Case 2 52 white male First spontaneous DVT 2000, OAT x 6 months Superficial phlebitis 2002 Second spontaneous DVT 2003 Factor V Leiden heterozygous 2 sons (20’s) and one daughter (18) Should his children be screened for FVL?

    34. VTE risk in thrombophilic FVL+ kindreds

    35. Case 3 A 55 year old woman is diagnosed with a DVT 2 weeks after removal of a cast for treatment of an ankle fracture. Thrombophilia testing is performed, and she is FVL heterozygous. Family history otherwise negative for VTEs. Should her 25 year old daughter who is taking OCPs be screened?

    36. VTE risk in unselected FVL kindreds

    37. Prospective study of VTE risk in FVL carriers

    38. conclusions Testing for thrombophilic risk factors, both inherited and acquired is recommended for selected patients at high risk for recurrent VTE Borderline low test results for antithrombin, protein C, and protein S should be viewed with great skepticism due to analytical impression and biologic variability D-dimer testing may be a useful “global test” to identify patients at lower risk for recurrent VTE Screening asymptomatic first degree relatives should be tempered by the identified risk factor in the affected proband, and by the “thrombophilic” severity of the kindred.

More Related