Antithrombotic Therapy for Pediatric VAD Patients

1. Antithrombotic Therapy for Pediatric VAD Patients Meloneysa Hubbard, MSN, CRNP, CCTC Director of Heart Transplant Services Children’s of Alabama

2. I do not have any relevant financial relationships with any commercial interests to disclose. Disclosure Statement

3. 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

4. Pediatric Ventricular Assist Devices • Berlin Heart EXCOR • FDA approved pediatric VAD • Pulsatile flow device • RVAD, LVAD, BiVAD • Thoratec PVAD • HeartWare, HeartMateII • SynCardia • PumpKIN Trial

5. Berlin Heart Implants Almond et al. Circulation 2013;127:1702-1711

7. Morbidity and Mortality Almond et al. Circulation 2013;127:1702-1711

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9. Coagulation Cascade • Feedback process of plasma protein activation • Results in converting prothrombin to thrombin • Thrombin • converts fibrinogen to fibrin • Activates platelets

10. Balance Thrombosis Bleeding

11. Considerations of Hemostasis • Immature coagulation • vWB factor deficiency • Heparin induced thrombocytopenia • Baseline hematology • Current hematology • Changes in patient status • Changes in nutrition

12. Laboratory Monitoring • Anti Xa • PTT • INR • TEG • Platelet Mapping / Platelet Aggregation

13. Thromboelastogram

14. Thromboelastogram Maximum amplitude (MA) -body of the clot formation -represents the ultimate clot strength -indicative of platelet activity -target range 55-73

15. Platelet Mapping • Platelet Mapping • Represents the inhibition present between clot fibrin and thrombin • Agent specific • ADP – clopidogrel, dipyridamole • AA - aspirin • Inhibition 70-95%

16. Platelet Mapping

17. Antithrombotic Agents • Unfractionated heparin • Antithrombin • Acetylsalicylic acid (ASA) • Dipyridamole • Clopidogrel • Low molecular weight heparin (enoxaparin) • Warfarin • Adjunctive Medications

18. 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

19. Heparin Target Dosing

20. Long Term Anticoagulation • Low molecular weight heparin • Catalyzes the interaction between thrombin and antithrombin • Monitor anti-Xa for target 0.6-1.0

21. Long Term Anticoagulation • Warfarin • Vitamin K antagonist • Monitor INR for target 2.5-3.5

22. 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 bid

23. Antiplatelet Therapy • Clopidogrel / Dipyridamole • Binds to adenosine di-phosphate receptors and prevents uptake • Initiated after POD 4 • Monitored by platelet mapping or aggregate studies

24. Anticoagulation

25. 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

27. Anticoagulation Guidelines Berlin Heart EXCOR 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 • 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

28. Patient Assessment • Pump function • Flows/Parameters • Chamber assessment • Physical assessment

29. 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

30. Question • Do you utilize INR Patient Home Monitoring for pediatric VAD patients? a) yes b) no

32. Quality of Life

33. 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.