Anticoagulation Strategies in MCS: Routine, Bleeding and ... · Rimsans et al (2017) Clinical and...
Transcript of Anticoagulation Strategies in MCS: Routine, Bleeding and ... · Rimsans et al (2017) Clinical and...
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Anticoagulation Strategies in MCS: Routine, Bleeding and the Heparin Resistant Patient
Mechanical Circulatory Support Symposium 2018 (Houston, TX)
Charles Hoopes, MDProfessor of SurgeryUniversity of Alabama (Birmingham)[email protected]
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Disclosure: I have no professional or financial relationship with any of the devices or technologies discussed.
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“Substantial variability remains in the approach to anticoagulant and antiplatelet therapy for patients on MCS, largely because of the lack of high-quality data.”
Anticoagulation with VADs and ECMO: walking the tightrope
L Raffini (2017) Hematology
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(1) device design and deployment (shear-induced platelet activation, blood path, pulsitility)
(2) anticoagulation (VKA + antiplatelet … DTI, Xa antagonists)
(3) monitoring (ACT, aPTT, PT/INR, Xa, TEG, LDH, pFHgb, microparticles)
(4) management (early ‘bridging’ and late surveillance, TTR)
Why is there a lack of consensus?
Given our general agreement on …
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Defining the problem …
Understanding the mechanism …
Measuring the intervention …
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Adatya and Bennett (2015)J Thorac Dis 7(12): 2129–2138
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… Technique, therapy,and management
Absent or short heparin bridgeInadequate INR targetTime in Therapeutic Range (TTR)Antiplatelet therapyBiomarkers (LDH) thresholds
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… a strong influence of outflow graft angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced thrombogenic potential for acutely-angled anastomosed outflow grafts.
Aliseda et al (2017) ASAIO 63: 14-23
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“… European-Americans with a variant of CYP2C9 (CYP2C9*2) required less of the drug according to race-specific dosing models, yet African-Americans did not. While all participants, regardless of race, who carried VKORC1 required lower dose, according to race-specific dosing models, the proportional dose reduction was greater among European-Americans.”
genotype-guided dosingrace-adjusted analysisrace-specific algorithms
“… algorithms - including clinical, genetic and environmental factors - to predict a patient’s risk of hemorrhage”
The Hugh Kaul Personalized Medicine Institute at UAB
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Prop of pop with poormedication compliance was 36% for anticoagulants(N=362, 10 years)
Source: US CommercialInsurance Database
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Sixteen patients randomized …
Half of the dabigatran patients had a thrombotic event …
Early termination …
Comparable to RE-ALIGN results …“Pradaxa” direct thrombin inhibition
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JHLT 2014 Jan;33(1):35-43
LDH > 600pfHgb > 40
… hemolysis induced pro-thrombotic state
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Significant discordance betweenaPTT and anti-FXa …
prolonged aPTT with INR >1.8
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Alvarez et al (2016) J Card Fail 22(7):501-11
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21 cases in 15 patients
Rimsans et al (2017) Clinical and Applied Thrombosis/Hemostasis 23(5) 405-409
10 cases in 6 patients
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• Bruckner et al (2009) High incidence of thromboembolic events. JHLT 28:785• Bradford et al (2015) Safety of prothrombin complex concentrate during LVAD insertion. ASAIO 61:509
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Platelets are aggregated by unfractionated heparin
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“… the VA ECMO weaning success rate was lower … and the in-hospital mortality higher for patients on continuous heparin infusion. We did not find any evidence … of thrombotic complications from heparin discontinuation.”
Chung et al (2017) ASAIO 63:32-36
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“The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient.”
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Artif Organs, Vol. 21, No. 9, 1997
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Contact activation versustissue factor mediated coagulation
CLS = clot life spanCGT = clot growth timeCLT = clot lysis time
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• standardized protocol, individual therapy
• a normocoagulable state in a prothromboticenvironment
• device specific
• CI (coagulation index) … (R, K, angle) + clot strength
• No differences in INR between TE and non-TE group
• Protocol: CI, INR, MA-AA, MA-ADP
• Fibrinogen and FVII … normal TEG R values and prolonged INR
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