1 / 40

Judicious Use of Anticoagulation: A Case-Based Approach

Judicious Use of Anticoagulation: A Case-Based Approach. Michael B. Streiff, MD, FACP Associate Professor of Medicine and Pathology Division of Hematology Medical Director, Johns Hopkins Anticoagulation Management Service and Outpatient Clinics. Research Funding Bristol-Myers Squibb

hastin
Download Presentation

Judicious Use of Anticoagulation: A Case-Based Approach

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. Judicious Use of Anticoagulation: A Case-Based Approach Michael B. Streiff, MD, FACP Associate Professor of Medicine and Pathology Division of Hematology Medical Director, Johns Hopkins Anticoagulation Management Service and Outpatient Clinics

  2. Research Funding Bristol-Myers Squibb NIH/NHLBI Consulting Sanofi-aventis Eisai, Inc. Daiichi-Sankyo Janssen Healthcare BiO2 Speaking Honoraria Sanofi-aventis Ortho-McNeil Educational Grants Sanofi-Aventis Covidien Disclosures

  3. Anticoagulation for pregnancy loss • 32 year old woman with 2 previous first trimester pregnancy losses asks about LMWH to prevent miscarriages. You advise her to • Start therapeutic dose LMWH • Start prophylactic dose LMWH • Start prophylactic dose LMWH + Aspirin 100 mg • Start no antenatal prophylaxis

  4. LMWH does not improve pregnancy outcomes: The ALIFE Study Placebo (N=121) Completed Study (N=103) 364 women with at least 2 pregnancy losses Aspirin 80 mg (N=120) Completed Study (N=97) Aspirin 80 mg + Nadroparin 2850 IU (N=123) Completed Study (N=99) Kaandorp S et al. NEJM 2010

  5. Baseline characteristics Kaandorp S et al. NEJM 2010

  6. LMWH did not increase the live birth rate Kaandorp S et al. NEJM 2010

  7. Thrombophilia did not affect live birth rate Kaandorp SP et al. NEJM 2010

  8. Anticoagulation does not prevent early pregnancy loss • Open-label RCT of enox 40 mg/d + ASA 75 mg vs. surveillance alone • PMHx ≥ 2 losses 24 weeks or less • Begin 7 weeks gestation or less • Conclusion- Prophylactic AC does not improve pregnancy outcomes N=294 Clark P et al. Blood 2010

  9. Heparin + Aspirin reduces pregnancy loss in Antiphospholipid Syndrome • Metanalysis of 5 RCTs of UFH/LMWH + aspirin versus aspirin • Regimens- UFH 5000-20000 units + aspirin 75-81 mg and LMWH 5000 + aspirin 75-81 mg • Conclusion- UFH/LMWH + ASA improves live birth rates RR 1.3 Mak A et al. Rheumatol 2010

  10. Anticoagulation- Less or More? • A 65 year old man with a St Jude aortic valve is scheduled to undergo a prostatectomy for cancer. When should he resume full-dose anticoagulation? • 12 hours post-op • 24 hours post-op • 36 hours post-op • 72 hours post-op

  11. Perioperative AC- Is less more? • Metanalysis of 34 studies of 12,278 patients • Outcomes- Thromboembolism and Bleeding • Limitation- Lack of RCT • Conclusion- Value of perioperative bridging unclear Siegal D et al. Circulation 2012

  12. Less is more for perioperative AC • Prospective Cohort of 1262 patients • Low risk- AVR w/o Afib-prophylactic LMWH • High risk- MVR, AVR w/Afib or stroke- Enox 0.7 mg/kg q12h • Post-op- resume AC day 1-3 based upon hemostasis Pengo V et al. Circulation 2009

  13. Thromboembolism Risk Stratification TE risk factors= A fib, Cardiac failure, HTN, DM, Age > 75, Stroke/TIA Douketis JD Blood 2011

  14. Bleeding Risk Assessment Spyropoulos AC and Douketis JD Blood 2012

  15. AC Management

  16. Anticoagulation for VTE • 65 year old man develops a right femoral-popliteal vein DVT 1 week after right knee replacement. A thrombophilia evaluation reveals he is heterozygous for the factor V Leiden mutation. How long should he be treated? • 6 weeks • 3 months • 12 months • Indefinite

  17. Anticoagulation for VTE • 48 year old man presents with progressive dyspnea over 1 week and left leg discomfort. CT angiogram identifies bilateral PE. Duplex study finds a left leg DVT. No VTE risk factors are identified. How long should he be treated? • 3 months • 6 months • 12 months • Indefinite

  18. Do the Results of Thrombophilia Tests Help to Determine Duration of Therapy? HR 2.0 (1.5-2.7) HR 1.8 (1-3.1) HR 1.4 (0.9-2.2) Recurrent VTE (%) HR 1.5 (0.8-2.8) (N= 570) 24 mos. (N=474) 84 mos. (N=267) 46 mos. (N=1626) 50 mos.

  19. Thrombophilia-Assessing the risk • High risk thrombophilia • Antithrombin deficiency - 1.8 % per year (95% CI 1.1-2.6%) • Protein C deficiency - 1.5% per year (1.1-2.1%) • Protein S deficiency - 1.9% per year (1.3-2.6%) • Moderate risk thrombophilia • Factor V Leiden - 0.5% per year (0.4-0.6%) • Prothrombin gene mutation - 0.3% per year (0.2-0.5%) • Factor VIII - 0.5% per year (0.4-0.5%) • Low risk thrombophilia • Factor IX - 0.1% per year (0.02-0.2%) • Factor XI - 0.2% per year (0.06-0.6%) • Hyperhomocysteinemia – 0.1% per year (0.05-0.3%) Lijfering WM et al. Blood 2009

  20. Antiphospholipid syndrome is associated with recurrent thromboembolism P=0.0013 Recurrent VTE (%) Months Schulman S , et al. Am J Med 1998; 104: 332-338

  21. VTE recurrence rate varies depending upon initial trigger for the event N = 570 Cumulative recurrent VTE (%) Time after cessation of therapy (months) Baglin T et al., Lancet 2003

  22. VTE Setting influences recurrence risk • Systematic review of prospective cohort studies and RCTs • 15 Studies • 5159 Subjects • Follow up- 3-96 months • Conclusion- Setting of thrombosis strongly influences recurrence rate Iorio A et al. Arch Intern Med 2010

  23. D dimer and recurrent VTE • D dimer- an indirect marker of activated coagulation • PROLONG study (Palareti G et al. NEJM 2006) • F/U 1.4 years • Systematic Review (Verhovsek M et al. Ann Intern Med 2008) • 7 studies, 1888 patients • Recurrent VTE- Abnl vs. nl DD (8.9% vs. 3.5% per year) N=608

  24. How do we identify the low risk patient with idiopathic VTE? • Prospective cohort study of 665 patients with idiopathic VTE • Enrolled at 12 centers, 4 countries prior to DC of warfarin after 5-7 months of therapy • Information of 76 laboratory and clinical variables associated with VTE were collected • Multivariate analysis used to develop clinical prediction rule for recurrent VTE • Results • F/U population 600/665 (90%) • Mean F/U -18 months (1-47 mos.) • Annual risk of recurrent VTE 9.3% per year (7.7%-11.3%) • Men 13.7% (10.8%-17%) • Women 5.5% (3.7%-7.8%) Rodger MA, et al. CMAJ 2008;179(5):417-26

  25. Clinical prediction rule for recurrent VTE in women Rodger MA, et al. CMAJ 2008;179(5):417-26

  26. Risk stratification for idiopathic VTE: The Vienna Risk Model http://www.meduniwien.ac.at/user/georg.heinze/zipfile/ViennaPredictionModel.html Eichinger S et al. Circulation 2010

  27. Thrombosis Bleeding Indefinite Anticoagulation: Weighing the risks

  28. Assessing Bleeding Risk: The HAS-BLED Score • HASBLED • Hypertension (uncontrolled SBP>160) = 1 point • Abnormal renal/liver function = 1 or 2 points • Stroke = 1 point • Bleeding (or anemia) = 1 point • Labile INRs (TTR<60%)= 1 point • Elderly (Age > 65 years)= 1 point • Drugs or alcohol= 1 or 2 points Pisters R et al. Chest 2010; Olesen JB, et al. JTH 2011

  29. Central Venous Catheter Prophylaxis • 67 year old man has just had a right subclavian Hickman CVC placed for chemotherapy for recently diagnosed NHL. What should be used for CVC thrombosis prophylaxis? • Warfarin 1 mg daily • Enoxaparin 40 mg daily • Dalteparin 5000 units daily • No prophylaxis necessary

  30. CVC Prophylaxis • Open RCT of low dose warfarin 1 mg vs. no warfarin • Start 3 days before CVC insertion • Outcome-Venogram with symptoms or at 90 days • Conclusion- Low dose warfarin prevents CVC thrombosis P<0.001 Bern MM et al. Ann Intern Med 1990

  31. Catheter Prophylaxis

  32. Adjusted dose warfarin prevents CVC thrombosis: WARP study • A multicenter (N=68) open label study of warfarin CVC prophylaxis (N=1590) • Study Arms- • No warfarin (404) vs. warfarin 1 mg (408) • Warfarin 1 mg (471) vs. warfarin (INR1.5-2.0) ( 473) • Conclusion- Dose-adjusted warfarin is required to prevent CVC DVT P=0.002 Young AM, et al. Lancet 2009

  33. Elevated INR- Less vitamin K is more • 70 year old man taking warfarin for atrial fibrillation has an INR of 7. He does not have any signs of bleeding. What should you do? • Hold warfarin and administer vitamin K 2.5 mg po • Hold warfarin and administer vitamin K 2.5 mg IV • Hold warfarin and recheck INR in 1-2 days • Hold warfarin and administer Vitamin K 2.5 mg and 3 units of FFP

  34. Less vitamin K is more safe • RCT of vitamin K 1.25 mg or placebo for pts. with INR 4.5-10 • Setting- 14 AC clinics in US, Canada, Italy • Outcomes- Symptomatic bleeding or thromboembolism within 90 days • Conclusion- Oral Vit K does not improve outcomes with INR 4.5-10 Crowther MA et al. Ann Intern Med 2009

  35. Is less is more? • 72 year old man with atrial fibrillation who has been on warfarin 5 mg daily for 3 months. Today his INR is 1.8. No reason identified. What should you do with his warfarin dose? • Increase his dose to 7.5 mg MWF, 5 mg ROW (21% dose increase), recheck 1 week • Increase his dose to 7.5 mg daily (50% dose increase), recheck 1 week • Increase his dose to 7.5 mg W, 5 mg ROW (7% dose increase, recheck 1 week • Continue same dose, recheck 1 week

  36. Less dose adjustment=more time in range • Observational study of warfarin management • Setting- 94 AC clinics, 3961 patients • Outcome- Time in therapeutic range • Conclusion- Excessive warfarin dose changes lead to poorer INR control Rose AJ et al. J ThrombHaemost 2009

  37. Is less LMWH more? • A 65 year old man with an atrial fibrillation (CHADS2 score 3) who has been on warfarin for 4 months has an INR of 1.5. Your nurse asks you for advice. You suggest… • LMWH + warfarin dose increase • Warfarin dose increase only

  38. Less LMWH is safe • Retrospective study of patients in Kaiser CO AC clinics • Low INR and therapeutic INR groups • Only 13 patients received LMWH • Outcomes- Bleeding and TE at 90 days • Conclusion- LMWH not necessary for most patients with low INR Clark NP et al. Pharmacother 2008

  39. Conclusions • Anticoagulation is not indicated for recurrent early pregnancy loss except perhaps APS • Therapeutic AC should be used sparingly in the post-operative period • Setting rather than presence of thrombophilia dictates duration of therapy • Risk stratification models can help determine the risk of recurrent VTE and bleeding in patients with idiopathic VTE • Central venous catheter prophylaxis remains of unproven benefit • Studies continue to optimize warfarin management

  40. Questions ?

More Related