antithrombotic therapy for pediatric vad patients meloneysa hubbard, msn, crnp, cctc director of...
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Antithrombotic Therapy for Pediatric VAD Patients
Meloneysa Hubbard, MSN, CRNP, CCTC
Director of Heart Transplant Services
Children’s of Alabama
I do not have any relevant financial relationships with any commercial interests to disclose.
Disclosure Statement
Objectives ?
Discuss the use of ventricular assist device (VAD) support in the pediatric population
Identify indications for antithrombotic therapy
Describe basic coagulation components
Discuss anticoagulation medications
Review our strategy for monitoring anticoagulation
Pediatric Ventricular Assist Devices Berlin Heart EXCOR
FDA approved pediatric VAD Pulsatile flow device RVAD, LVAD, BiVAD
Thoratec PVAD
HeartWare, HeartMate II
SynCardia
PumpKIN Trial
Berlin Heart Implants
Almond et al. Circulation 2013;127:1702-1711
Morbidity and Mortality
Almond et al. Circulation 2013;127:1702-1711
这是凝血过程是很容易理解是否你一定要把它理解成你的理解。
Coagulation Cascade
• Feedback process of plasma protein activation
• Results in converting prothrombin to thrombin
• Thrombin • converts
fibrinogen to fibrin• Activates platelets
Balance
Thrombosis Bleeding
Considerations of Hemostasis
Immature coagulation vWB factor deficiency Heparin induced thrombocytopenia Baseline hematology Current hematology Changes in patient status Changes in nutrition
Laboratory Monitoring
Anti Xa
PTT
INR
TEG
Platelet Mapping / Platelet Aggregation
Thromboelastogram
Thromboelastogram
Maximum amplitude (MA)
-body of the clot formation
-represents the ultimate clot strength
-indicative of platelet activity
-target range 55-73
Platelet Mapping
Platelet Mapping Represents the inhibition present
between clot fibrin and thrombin Agent specific
ADP – clopidogrel, dipyridamole AA - aspirin
Inhibition 70-95%
Platelet Mapping
Antithrombotic Agents Unfractionated heparin
Antithrombin
Acetylsalicylic acid (ASA)
Dipyridamole
Clopidogrel
Low molecular weight heparin (enoxaparin)
Warfarin
Adjunctive Medications
Anticoagulation Therapy
Heparin Catalyzes the interaction between
thrombin and antithrombin Requires adequate ATIII level <70% Initiated 24-48 hours after implant
Platelet count 50,000 TEG MA >56 No significant bleeding
Therapeutic monitoring with anti Xa
Heparin Target DosingStage Age
(months)Anti-factor XA
(u/ml)PTT (sec)
Infusion rate
HoldUFH
%Rate Change
RepeatAnti-Xa(or PTT)
I Therapeutic Range
All
10-20 u/kg/h
After 6hrs
II
Adjustment
<3 mo
Max PTT85 sec
<0.1 (<50)
No +15% 4hrs
0.1-0.34 (50-59)
No +10% 6hrs
0.35-0.50 (60-
85)
No 0
As per guideline
0.51-0.70 (86-
95)
No -10% 6hrs
0.71-.89(96-120) 30 min. -10% 4hrs
≥ 0.90 (>120) 60 min. -15 % 4hrs
II
Adjustment
≥ 3 mo
Max PTT95 sec
<0.1 (<50)
No +15% 4hrs
0.1-0.34 (50-59)
No +10% 6hrs
0.35-0.70 (60-95)
No 0 As per guideline
0.71-.89(96-120) 30 min. - 10% 4hrs
≥ 0.90 (>120) 60 min. -15 % 4hrs
Long Term Anticoagulation Low molecular weight heparin
Catalyzes the interaction between thrombin and antithrombin
Monitor anti-Xa for target 0.6-1.0Anti-Factor Xa
level u/mlHold Next Dose?
Dose Change
Repeat Anti-Factor Xa
< 0.35 No Increase by 25% 4 hours after next dose 0.36 - 0.45 No Increase by 15% 4 hours after next dose0.46 - 0.59 No Increase by 10% 4 hours after next dose
6. - 1.0
No No 4 hours after next dose
1.1 - 1.25 No Decrease by 20% 4 hours after next dose
1.26 - 1.5 No Decrease by 30% 4 hours after next dose1.6 – 2.0 Yes, for 3 hours Decrease by 40% Before next dose then 4 hours
after next dose> 2.0 Yes, until anti-factor Xa
level is ≤ 0.6 u/mlDecrease by 50 % Before next dose, if anti-Xa level
>0.6 U/ml, repeat level q12h until ≤0.6 U/ml before re-starting at 50% of previous dose
Long Term Anticoagulation
Warfarin Vitamin K antagonist Monitor INR for target 2.5-3.5
Stage
INR
Action
Day 1 1.0 – 1.8 0.2 mg/kg orally
Day 2-4
1.1 – 1.3 Repeat day 1 loading dose1.4 – 1.9 50% of day 1 loading dose2.0 – 3.0 50% of day 1 loading dose3.1 – 3.5 25% of day 1 loading dose
> 3.5 Hold dosing until INR is < 3.5
Maintenance ≥ Day 5 and long term
1.1 – 1.9 Increase dose by 40 – 50%2.0 – 2.6 Increase dose by 20 – 30%2.7 – 3.5 No change3.6 – 4.0 Administer next dose at 50%, then restart at 20% less
maintenance dose4.1 – 5.0 Hold one dose then repeat INR; if 2-3 decrease dose 50%
Antiplatelet Therapy Aspirin
Blocks arachidonic acid pathway of platelet activation
Usually started >48 hours after implant Monitored by TEG and platelet mapping or
aggregate studies May be indicated bidArachidonic acid platelet inhibition
Hold next dose?
Dose change? Repeat AA Test?
0-30% No Increase 100% Next day31-50% No Increase 50% Next day51-69% No Increase 25% 48 hours70-95% No No As per guideline96-100% No Decrease 10% 48 hours100% and patient is bleeding
Yes Hold next dose until bleeding stops, decrease 50%
Next day
Antiplatelet Therapy
Clopidogrel / Dipyridamole Binds to adenosine di-phosphate receptors
and prevents uptake Initiated after POD 4 Monitored by platelet mapping or aggregate
studiesADP platelet inhibition
Hold next dose?
Dose change? Repeat AA Test?
0-30% No Increase 100% Next day31-50% No Increase 50% Next day51-69% No Increase 25% 48 hours70-95% No No As per guideline96-100% No Decrease 10% 48 hours100% and patient is bleeding
Yes Hold next dose until bleeding stops, decrease 50%
Next day
Anticoagulation
Question
A 2 month old patient supported with Berlin Heart LVAD is stable with no signs of active bleeding or pump fibrin deposits. Anticoagulation
ASA 5mg/kg clopidogrel 0.2mg/kg Warfarin 0.5mg/kg
Labs TEG/PM: MA 68; AAI
80%; ADPI 53% INR 2.1
What would you anticipate for this patient? a) continue to monitor b) increase warfarin c) increase warfarin and
clopidogrel d) increase warfarin and
decrease aspirin
Anticoagulation Guidelines
Berlin Heart EXCOR Heparin Drip
Inhibits coagulation pathway started 24-48 hours after implant Titrated to goal Anti Xa 0.35-0.5 U/mL Stopped once Coumadin is
therapeutic
Coumadin Inhibits coagulation pathway Started once bleeding resolved and
tolerating PO Titrated to goal INR 2.5-3.5
Aspirin Blocks arachidonic acid pathway of
platelet activation Dosed for goal AA inhibition 70-95 %
Clopidogrel (Plavix) Blocks adenosine di-phosphate
pathway of platelet activation Dosed for goal ADP inhibition 70-90% May be used as long-term therapy
HeartWare HVAD Heparin Drip
Inhibits coagulation pathway
started 24-48 hours after implant
Titrated to goal Anti Xa 0.35-0.5 U/mL
Stopped once Coumadin is therapeutic
Coumadin Inhibits coagulation pathway
Started once bleeding resolved and tolerating PO
Titrated to goal INR 2.0-3.0
Aspirin Blocks arachidonic acid pathway of
platelet activation
Dosed for goal AA inhibition 70-95%
Clopidogrel (Plavix) Blocks adenosine di-phosphate pathway
of platelet activation
Dosed for goal ADP inhibition 70-90%
Stopped once Coumadin is therapeutic
Patient Assessment
Pump function
Flows/Parameters
Chamber assessment
Physical assessment
Patient Care Education Medication
Indication Administration/dosage Side effects Monitoring Interactions
Physical Activity Precautions
Dietary Considerations
Illness effects
Complications of device support/anticoagulation
Home monitoring
Question
Do you utilize INR Patient Home Monitoring for pediatric VAD patients?
a) yes
b) no
Quality of Life
References
Almond, C., Morales, D., Blackstone, E., Turrentine, M., Imamura, M., Massicotte, P., Jordan, L., Devaney, E., Ravishankar, C., Kanter, K., Holman, W., Kroslowitz, R., Tjossem, C., Thuita, L., Cohen, G., Buchholz, H., St. Louis, J., Nguyen, K., Neibler, R., Walters, H., Reemtsen, B., Wearden, P., Reinhartz, O., Guleserian, K., Mittchell, M., Bleiweis, M., Canter, C., Humpl, T., (2013). Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation, 127:1702-171
Zafar, F., Chasleberry, C., Khan, M., Mehta, V., Bryant, R., Lorts, A., Wilmot,I., Jefferies, J., Chin, C., Morales, D., (2015). Pediatric heart transplant waiting list mortality in the era of ventricular assist devices. Journal of Heart and Lung Transplantation, 34:1, 82-86.
Drews, T., Kupper, F., Stiller, B., Hubler, M., Weng, Y., Berger, F., Hetzer, R., (2007). Coagulation management in pediatric mechanical circulatory support. ASAIO Journal, 53: 640-645.
Moffett, B., Gabrera, A., Teruya, J., Bomgaars, L., (2014). Anticoagulation therapy trends in children supported by ventricular assist devices: a multi-institutional study. ASAIO Journal, 60:2, 211-215
Massicotte, M., Bauman, M., Murray, J., Almond, C., (2015). Antithrombotic therapy for ventricular assist devices in children: do we really know what to do?, (2015). 13, S343- 345.