Lack of standardization in ventricular assist device [VAD] - Does it matter ?

1. DEPARTMENT NAME
Marc Anders,
Critical Care Medicine, Texas Children’s Hospital
Assistant Professor of Pediatrics, Baylor College of Medicine
Houston, Texas, USA
LACK OF STANDARDIZATION IN
ANTICOAGULATION – DOES IT MATTER ?
CRITICAL CARE MEDICINE

2. DEPARTMENT NAMECRITICAL CARE MEDICINE

3. DEPARTMENT NAME
DEVELOPMENTAL HEMOSTASIS
Developmental hemostasis: A lifespan from neonates and pregnancy to the young and elderly adult in a European white population.
Nowak-Göttl U et al. Blood Cells Mol Dis. 2016 Dec 5
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4. DEPARTMENT NAME
DEVELOPMENTAL HEMOSTASIS
Developmental haemostasis: Impact for clinical haemostasis laboratories
Monagle P et al. Thromb Haemost 2006; 95: 362–72
CRITICAL CARE MEDICINE

5. DEPARTMENT NAME
PEDIMACS
Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for
Mechanical Circulatory Support (PediMACS). Blume ED et al. J Heart Lung Transplant. 2016 May;35(5):578-84
CRITICAL CARE MEDICINE

6. DEPARTMENT NAME
PEDIMACS – SIZE MATTERS…
Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for
Mechanical Circulatory Support (PediMACS). Blume ED et al. J Heart Lung Transplant. 2016 May;35(5):578-84
CRITICAL CARE MEDICINE

7. DEPARTMENT NAME
Modified Implantation technique
VAD PERFORMANCE CHARACTERISTICS
A modified implantation technique of the HeartWare ventricular assist device for pediatric patients
Adachi et al. J Heart Lung Transplant. 2015 Jan;34(1):134-36
CRITICAL CARE MEDICINE

8. DEPARTMENT NAME
ACTIVATION ON ENDOTHELIAL HEMOSTASIS
Activation of endothelial and coagulation systems in left ventricular assist device recipients.
John R et al Ann Thorac Surg. 2009 Oct;88(4):1171-9
CRITICAL CARE MEDICINE

9. DEPARTMENT NAME
ACQUIRED VON WILLEBRAND SYNDROME
Platelet dysfunction and acquired von Willebrand syndrome in patients with left ventricular assist devices.
Baghai M et al. Eur J Cardiothorac Surg. 2015 Sep;48(3):421-7
CRITICAL CARE MEDICINE

10. DEPARTMENT NAME
INFLAMMATION ON VAD
Severity of oxidative stress and inflammatory activation in end-stage heart failure patients are unaltered after 1 month of left ventricular
mechanical assistance. Caruso R et al. Cytokine 2012. Jul;59(1):138-44.
CRITICAL CARE MEDICINE

11. DEPARTMENT NAME
VAD
THROMBOSIS /
BLEEDING
avWS
High
Afterload
Clotting
Disorders
Inflammation
Device
Type
Mechanical
Factors
Infection
Developmental
Hemostasis
CRITICAL CARE MEDICINE

12. DEPARTMENT NAME
VAD
THROMBOSIS /
BLEEDING
avWS
High
Afterload
Clotting
Disorders
Inflammation
Device
Type
Mechanical
Factors
Infection
Developmental
Hemostasis
Antiplatelet
Therapy
Systemic
Anticoagulation
CRITICAL CARE MEDICINE

13. DEPARTMENT NAME
UFH LMWH
MW (Da) 3.000 – 30.000 2.000 – 9.000
Clearance
HMW more
rapidly
More
predictable.
Renal
Pharmaco-
dynamic effect
Binds to AT Binds to AT
Monitoring
ACT
aPTT
Anti - Xa
Anti-Xa
PARENTERAL ANTICOAGULATION - HEPARIN
CRITICAL CARE MEDICINE

14. DEPARTMENT NAME
HEPARIN - MONITORING
CRITICAL CARE MEDICINE

15. DEPARTMENT NAME
HEPARIN - MONITORING
Gold standard in anticoagulation assessment of left ventricular assist device patients?: how about bronze.
Stehlik J et al. JACC Heart Fail. 2015 Apr;3(4):323-6
CRITICAL CARE MEDICINE

16. DEPARTMENT NAME
HEPARIN - MONITORING
Interlaboratory variation in heparin monitoring: Lessons from the Quality Management Program of Ontario coagulation surveys
Cuker A et al. Thromb Haemost. 2010 Oct;104(4):837-44
CRITICAL CARE MEDICINE

17. DEPARTMENT NAME
ARGATROBAN BIVALIRUDIN
MW (Da) 1.700 Da 2.200 Da
Clearance hepatic
20% renal, 80%
hepatic
Pharmaco-
dynamic effect
direct TI direct TI
Monitoring
aPTT
ECT
aPTT
ECT
PARENTERAL ANTICOAGULATION - DTI
Antithrombotic strategies in children receiving long-term Berlin Heart EXCOR ventricular assist device therapy.
Rutledge JM et al. J Heart Lung Transplant. 2013 May;32(5):569-73
CRITICAL CARE MEDICINE

18. DEPARTMENT NAME
PARENTERAL ANTICOAGULATION - ANTITHROMBIN
Antithrombin use in pediatric ventricular assist device – a review of the PHIS database.
Anders M, Tume S. 2017 [unpublished data]
CRITICAL CARE MEDICINE

19. DEPARTMENT NAME
ENTERAL ANTICOAGULATION – VKA
Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement.
Moreau C. et al. Blood 2012 Jan 19; 119(3): 861 - 867
CRITICAL CARE MEDICINE

20. DEPARTMENT NAME
ENTERAL ANTICOAGULATION – ANTIPLATELET
Anticoagulation therapy trends in children supported by ventricular assist devices: a multi-institutional study.
Moffett BS et al. ASAIO J. 2014 Mar-Apr;60(2):211-5
CRITICAL CARE MEDICINE

21. DEPARTMENT NAME
DOES ANTICOAGULATION MATTER ?
1 Prospective trial of a pediatric ventricular assist device.
Fraser CD Jr et al. N Engl J Med. 2012 Aug 9;367(6):532-41
2 Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device.
Steiner ME et al. ASAIO J. 2016 Nov/Dec;62(6):719-727
SAE
Cohort
1 and 2
directly
related to
Anti-
coagulation
Major bleeding 43 % 24 %
Neurological
compication
28 % 9 %
Hemolysis 4 %
Arterial non-CNS
thrombosis
3 %
CRITICAL CARE MEDICINE

22. DEPARTMENT NAME
THE EDMONTON BH ANTICOAGULATION
Prospective trial of a pediatric ventricular assist device.
Fraser CD Jr et al. N Engl J Med. 2012 Aug 9;367(6):532-41
CRITICAL CARE MEDICINE

23. DEPARTMENT NAME
DOES ANTICOAGULATION MATTER ?
Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device.
Steiner ME et al. ASAIO J. 2016 Nov/Dec;62(6):719-727
CRITICAL CARE MEDICINE

24. DEPARTMENT NAME
ANTICOAGULATION FOR VAD GUIDELINE
HeartWare HeartMate II Syncardia TAH
• after 24 hours titrate
Heparin to PTT 40 – 50
• gradually increase to PTT 50-
60
• after 24 hours start Aspirin
325mg OD
• titrate by PTT 1.2 – 1.4
• after 24 hours titrate PTT
1.4-1.7
• after 48 hours titrate PTT
1.5-1.8
• start Aspirin (81 – 100mg)
QD and Dipyramidole
75mg TID
• no anticoagulation for 24 hours
• after 24 hours titrate Heparin to
PTT 40 – 50
• after 48 hours titrate Heparin to
PTT 50 – 60
Start Warfarin, check platelet
function (add Dipyramidole or
Clopidogrel if resistance)
Start Warfarin, continue
Aspirin and Dipyramidole
after 1 week – starting Coumadine
and Aspirin 100 mg/day
Target INR: 2.0 – 3.0 Target INR: 2.0 – 3.0 Target INR: 2.5 – 3.5
CRITICAL CARE MEDICINE

25. DEPARTMENT NAMECRITICAL CARE MEDICINE

26. DEPARTMENT NAME
COMMENTS/QUESTIONS?

27. DEPARTMENT NAME
Does small size really matter ?
VAD PERFORMANCE CHARACTERISTICS
Does Small Size Matter With Continuous Flow Devices?: Analysis of the INTERMACS Database of Adults With BSA ≤1.5 m2.
Zafar F et al. JACC Heart Fail. 2017 Feb;5(2):123-131
Significant more bleeding events !
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