Anticoagulation workshop David Dale, MD MACP Eric Gamboa, MD FACP IyadHamarneh, MD September 13, 2014
Case #1 • 51 year old male • developed two unprovoked pulmonary emboli • has been on warfarin for many years but was tired of the INR monitoring and diet restrictions • his PCP referred him for opinion regarding switching to the new oral anticoagulants • has mild renal insufficiency with GFR in the mid 50's • How would you manage this patient? • Is he a candidate for rivaroxaban?
Rivaroxaban is a direct factor Xa inhibitor • Approved for the treatment of VTE and nonvalvular atrial fibrillation • Usual dose is 20 mg daily • No dose reduction required for mild renal insufficiency • No specific antidote • NON-dialyzable • PCC has been shown to reverse anticoagulant effect in a small study (Eerenberg, et al. Circulation. 2011)
Case #2 • 63 year old male • has been on chronic warfarin for repeat episodes of VTE's • attempts to discontinue anticoagulation by his PCP led to episodes of repeat thrombosis • has been suffering from back pain and was noted to have disk herniation for which surgery has been recommended • neurosurgeon consulted his hematologist/oncologist for the proper way to hold warfarin in the perioperative period in order to avoid bleeding but at the same time minimize possibility of thrombosing • How would you advise interrupting warfarin?
Case #3 • 78 year old female • history of atrial fibrillation • was on dabigatran • developed gastric ulcer bleeding • presented to the ER with continued bleeding, hypotension and severe anemia • If you were consulted by the cardiologist and intensivist regarding management of bleeding, what would be your advice?
Dabigatran is a direct thrombin (factor IIa) inhibitor • Approved for the treatment of VTE and nonvalvular atrial fibrillation • Anticoagulant effect persists despite repletion of factor II (prothrombin) • Usual dose is 150 mg PO BID • No dose reduction required for mild renal insufficiency unless patient is on concomitant P-gp inhibitor • No specific antidote • Dialyzable • PCC did NOT reverse anticoagulant effect in a small study (Eerenberg, et al. Circulation. 2011)
Case #4 • 67 year old female • developed unprovoked DVT • completed 6 months of warfarin therapy • If you were asked by the PCP when and if warfarin can be stopped, what would be your advice?
403 patients with a first-ever unprovoked VTE who completed 6-18 months of anticoagulation were randomized to receive aspirin 100 mg vs. placebo. • Primary efficacy outcome was recurrence of VTE • Secondary outcome was major bleeding • Recurrent VTE occurred in 6.6% in the aspirin patients vs. 11.2% in the placebo patients (HR 0.58; 95% CI 0.33-0.92) • Bleeding was the same in both groups
Case #5 • 47 year old male • history of a provoked DVT in 2005 (testicular trauma) • underwent hypercoagulablework up which was positive for Lupus anticoagulant • referred to rheumatology and subsequently diagnosed with SLE • treated with plaquenil for 4 years until 2009 • has been on Coumadin since 2005 • No other episodes of DVTs • Patient was sent to evaluate the need for further anticoagulation • Coumadin was discontinued • Weeks after stopping Coumadin he suffered flare of SLE with renal failure, proteinuria, pancytopenia and subsequently another episode of DVT • What would you do now?
Case #6 • 67 year old male • history of unprovoked right LE DVT • finished 10 months of anticoagulation with Coumadin • no personal or family history of DVTs • one of siblings tested positive for an MTHFR mutation • PCP sent the patient for a hematology consult mostly for MTHFR testing and duration of anticoagulation • Would you continue Coumadin? • Would you test for MTHFR mutation?
Case #7 • 26 year old female with multiple DVTs • known to be heterozygous for Factor V Leiden and protein S deficiency • has strong family history of Protein S deficiency and multiple DVTS on her father’s side of the family • during her first pregnancy had DVT, no PE; treated with Lovenox for 6 weeks after delivery • during second pregnancy had DVT with PE; treated with Lovenox and Coumadin. Duration of Coumadin unknown and stopped due to loosing her insurance • during third pregnancy had PE; treated with Lovenox and Coumadin afterward for a total of 9 months. • during pregnancy in August 2014 diagnosed with DVT while on 1.5 mg per kg of Lovenox. • What would you do now?
Case #8 • 62 year old male • history of familial P.vera and DVT • developed a PE after driving for 12 hours while on Coumadin • INR was subtherapeutic at 1.4 • he was switched to Lovenox after discharge from the hospital • he was readmitted to the hospital with sepsis and acute renal failure • was kept on the same dose of LovenoxDESPITE his declining renal function • developed a large right knee hemarthrosis • Lovenoxwas stopped and he was switched to heparin drip • Hematology consult for anticoagulation after discharge • GFR is ~ 15 • What would you recommend now?
Case #9 • 61 year old male • prostate cancer and a history of provoked DVT • on anticoagulation with Coumadin • has large thoracic vertebral metastasis which was treated with radiation • sustained a fall while working in the backyard which led to an ER visit • in the ER was started on ketorolac 10 mg PO TID which helped with the pain • 10 days after starting NSAIDS he presented with melena and was found to have erosive gastritis. • What would you do now?
References • Miller C, etal. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol. 2012;110:453-60 • Becattini C, etal. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-67 • Eerenberg ES, etal. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573-9 • Guyatt GH, etal. Antithrombotic therapy and prevention of thrombosis, 9thed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesChest. 2012;141;7S-47S. • Imberti D, etal. Practical management of rivaroxaban for the treatment of venous thromboembolism. ClinApplThrombHemost. 2013 Oct 16 [Epub ahead of print] • Kuderer NM, etal. Guidelines for treatment and prevention of venous thromboembolism among patients with cancer. Thromb Res. 2014;133 Suppl 2;S122-7