Anticoagulation: review of best practices
INTERMACS 9th Annual Meeting
May 16, 2015
Salpy V. Pamboukian MD MSPH
University of Alabama at Birmingham, Birmingham, AL
Outline
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Perioperative
Post-operative/long term
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INR goals
Anti-platelets
Monitoring
Management
Complications
• GI bleed
• Stroke
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Hemorrhagic
Ischemic
Pump thrombosis
Infection
Guidelines
Durable, continuous flow devices
Early practice: 2000’s
• Immediate post operative heparin (or alternative)
bridging on POD 0-1 or when CT drainage < 50ml/hr
• Target PTT 45-50, then stepwise to 55-65
• Warfarin
• ASA 81-325mmHg
• Other anti-platelets
• Dipyridamole 75mg TID
• HeartMate II warfarin target 2-3
• HeartWare warfarin target > 1.7, changed to 2-3 in
2011
Pump design changes
• HeartWare sintered pump  spring 2011
Najjar S et al. JHLT 2014; 33:23-34
Pump design changes
• Heart Mate II
• pre-clotted graft phased in 2011
• Bend relief recall in Feb 2012
• device labeling revised to provide instructions on how to verify the
bend relief is fully engaged with the sealed outflow graft at the time
of implant
Use of IV heparin post operatively:
do we really need it?
• HeartMate II BTT LVAD
patients
-418 patients
-3 groups
-35 centers
• Retrospective analysis of
patients enrolled in the
clinical trial
• Groups were defined based
on PTT on days 3,5,7,10,14
• Outcomes: ischemic,
hemorrhagic stroke, pump
thrombosis, bleeding > 2U
• Average duration of support
was 293 + 263 days
Slaughter et al. JHLT 2010; 29:616-24
Bleeding or Thrombotic Adverse Event
Many centers moved away from use of IV heparin bridging post operatively
What do the guidelines say….
Feldman D, Pamboukian SV, Teuteberg JJ et al. JHLT 2013 Feb;32(2):157-87
Feldman D, Pamboukian SV, Teuteberg JJ et al. JHLT 2013 Feb;32(2):157-87
Long term anticoagulation: considerations
• Balancing bleeding and thromboembolism risk
• GI bleeding risk up to ~30%
• Stroke risk 8-18%
• Co-morbid conditions
• Mechanical valves
• Atrial fibrillation
• Pulmonary embolism
What are ideal INR targets?
Optimal INR
Boyle A et al. JHLT 2009;28: 881–7
Although the initial concerns related to continuous flow LVADs were related to
the risk of thrombosis and thromboembolism, it is apparent that thrombotic
events are significantly overshadowed by the frequency of hemorrhagic
events. The appropriate target INR range for HeartMate II patients should be
chosen to minimize the risk of devastating hemorrhagic and ischemic strokes,
while reducing the incidence of major bleeding. The original protocol suggested
a target INR of 2 to 3. This analysis shows that most patients were actually
managed in the INR range of 1.5 to 2.5 and that in this range, the risks of
thrombosis and hemorrhage seem balanced. This therefore seems like an
appropriate target INR range for most HeartMate II patients.
Observed increase in pump thrombosis
Kirklin et al. JHLT 2014; 33: 12-22
What do the guidelines say….
Feldman D, Pamboukian SV, Teuteberg JJ et al. JHLT 2013 Feb;32(2):157-87
Feldman D, Pamboukian SV, Teuteberg JJ et al. JHLT 2013 Feb;32(2):157-87
Antiplatelet therapy
• ASA 80-325mg daily
• Clopidogrel 75mg daily
• Dipyridamole 75-100mg three times daily
Axial Flow
Kreuziger et al. Journal of Thrombosis and Hemostasis, Mar 2015
Axial Flow
• TE events were lower in patients with ASA/D vs. ASA
• 10% vs. 19%, RR 0.50 (CI 0.36-0.68)
• Stroke was lower in ASA/D vs. ASA
• 6% vs. 10%, RR 0.58 (CI 0.37-0.93)
• VAD thrombosis was lower in ASA/D vs. ASA vs. None
• 4% vs. 11% vs. 5%
• Three studies of patients treated without ASA reported similar rates of TE,
stroke as those with ASA use
• Hypothesis generating: different devices, INR goals and patient
characteristics
Kreuziger et al. Journal of Thrombosis and Hemostasis, Mar 2015
Centrifugal
Kreuziger et al. Journal of Thrombosis and Hemostasis, Mar 2015
Newer agents
• Newer oral anticoagulant and anti-platelet agents
such as rivaroxaban (Xarelto®), dabigatran
(Pradaxa®), apixaban (Eliquis®), ticagrelor (Brilinta®)
and prasugrel (Effient®) have not been studied in
MCS patients and cannot be recommended
Monitoring of therapy
• Heparin: PTT vs anti Xa
• Warfarin
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INR
• Frequency
• MCS team, Anti-coagulation clinic
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Home monitoring machine
• Alere device had moderate correlation with venous INR values of 0.83 with
median difference of 0.391
• Majority recorded higher INR’s with Alere
• ASA
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TEG
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Platelet aggregation
1. Dionizovik-Dimanovski et al. ASAIO April 2015
Feldman D, Pamboukian SV, Teuteberg JJ et al. JHLT 2013 Feb;32(2):157-87
What to do when….
• Subtherapeutic
• enoxaparin bridging
• Supratherapeutic
• Reversal with vitamin K
• FFP
• Prothrombin complex concentration (PCC)
• Factor VII
• In a small series of 25 patients, 1/38 reversal attempts
resulted in TE event
• Patient received high dose Factor VII
• Majority received IV vitamin K 10mg and FFP
• 5/25 died, 3 from ICH, 2 from sepsis
Jennings et al. ASAIO 2014; 60:381-384
Interruption of therapy for procedures
• In a meta-analysis of ~ 2100 patients undergoing
CIED uninterrupted use of OAC w/ therapeutic INR
was associated with reduced risk of bleeding
compared with heparin bridging with no difference
in TE rates1
Sant’anna et al. Pacing Clin Electrophysiol. 2015 Apr;38(4):417-23.
What to do when complications arise….
• GI bleed
• Stroke
• Ischemic
• Hemorrhagic
• Pump thrombosis
• Infection
GI bleeding
Guha et al. Methodist Debakey Cardiovasc J. Jan-Mar 2015
Observations
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ISHLT MCS guidelines reflect current practice
Little supporting evidence
Non- randomized data may lead us astray
Need standardized protocols that can be
prospectively tested
• This will be best accomplished if centers collaborate
• Given the “high stakes” nature of MCS therapy,
ultimately clinicians will need to balance evidence
versus individual considerations
It’s complicated