Anticoagulation - What`s New in Medicine

David Dale, MD MACP
Eric Gamboa, MD FACP
Iyad Hamarneh, 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
• Approved for the treatment of
VTE and nonvalvular atrial
• 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
 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
 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
• 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
• 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 0.330.92)
Bleeding was the same in both groups
Case #5
 47 year old male
 history of a provoked DVT in 2005 (testicular trauma)
 underwent hypercoagulable work up which was positive for Lupus
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
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 Lovenox DESPITE his declining renal
developed a large right knee hemarthrosis
Lovenox was 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
 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?
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,
9th ed: American College of Chest Physicians Evidence-Based Clinical
Practice Guidelines Chest. 2012;141;7S-47S.
Imberti D, etal. Practical management of rivaroxaban for the treatment
of venous thromboembolism. Clin Appl Thromb Hemost. 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

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