Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices.

BACKGROUND Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. METHODS For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. RESULTS Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. CONCLUSIONS Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients.

[1]  Christoph Benk,et al.  Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease. , 2008, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[2]  G. Di Minno,et al.  Aspirin resistance, platelet turnover, and diabetic angiopathy: a 2011 update. , 2012, Thrombosis research.

[3]  R. Marchant,et al.  Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. , 1996, Blood.

[4]  R. Hebbel,et al.  Activation of endothelial and coagulation systems in left ventricular assist device recipients. , 2009, The Annals of thoracic surgery.

[5]  S. Russell,et al.  Advanced heart failure treated with continuous-flow left ventricular assist device. , 2009, The New England journal of medicine.

[6]  J. Geiger,et al.  Monitoring of clopidogrel action: comparison of methods. , 2005, Clinical chemistry.

[7]  D. Danielak,et al.  Genetic and non-genetic factors affecting the response to clopidogrel therapy , 2012, Expert opinion on pharmacotherapy.

[8]  F. Michal,et al.  Effect of the rapid shape change of platelets on the transmission and scattering of light through plasma. , 1971, Nature: New biology.

[9]  G. Maurer,et al.  Personalized antiplatelet treatment after percutaneous coronary intervention: the MADONNA study. , 2013, International journal of cardiology.

[10]  S. Russell,et al.  Bleeding complications and blood product utilization with left ventricular assist device implantation. , 2011, The Annals of thoracic surgery.

[11]  K. Hornik,et al.  A Lego System for Conditional Inference , 2006 .

[12]  L. Aledort,et al.  Functional changes in platelets during extracorporeal circulation. , 1975, The Annals of thoracic surgery.

[13]  S. Schulman,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients , 2005, Journal of thrombosis and haemostasis : JTH.

[14]  M. Price,et al.  Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. , 2012, Journal of the American College of Cardiology.

[15]  M. Slaughter,et al.  Acquired von Willebrand Syndrome in Patients With an Axial Flow Left Ventricular Assist Device , 2010, Circulation. Heart failure.

[16]  Martin Strueber,et al.  Multicenter evaluation of an intrapericardial left ventricular assist system. , 2011, Journal of the American College of Cardiology.

[17]  Ranjit John,et al.  Bleeding and Thrombosis in Patients With Continuous-Flow Ventricular Assist Devices , 2012, Circulation.

[18]  A. Schmaier,et al.  Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the platelet physiology subcommittee of SSC/ISTH , 2013, Journal of thrombosis and haemostasis : JTH.

[19]  P. Gurbel,et al.  Earlier recovery of platelet function after discontinuation of treatment with ticagrelor compared with clopidogrel in patients with high antiplatelet responses , 2011, Journal of thrombosis and haemostasis : JTH.

[20]  V. Addonizio Platelet function in cardiopulmonary bypass and artificial organs. , 1990, Hematology/oncology clinics of North America.

[21]  J. Goudemand,et al.  Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM‐1VWD) , 2008, Journal of thrombosis and haemostasis : JTH.

[22]  Roland Hetzer,et al.  Retrospective Hemolysis Comparison Between Patients With Centrifugal Biventricular Assist and Left Ventricular Assist Devices , 2011, ASAIO journal.

[23]  P. Leprince,et al.  HeartMate II left ventricular assist device; early European experience. , 2008, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[24]  P. McCarthy,et al.  Hemostatic profiles of HeartMate ventricular assist device recipients. , 1995, ASAIO journal.

[25]  D Bergqvist,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients , 2010, Journal of thrombosis and haemostasis : JTH.

[26]  Y. Misawa,et al.  Platelet damage caused by the centrifugal pump: in vitro evaluation by measuring the release of alpha-granule packing proteins. , 2008, Artificial organs.

[27]  G. Esposito Responsiveness to P2Y12 receptor inhibitors , 2011, Current opinion in cardiology.

[28]  L. Nielsen,et al.  Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). , 2009, Journal of the American College of Cardiology.

[29]  M. Olschewski,et al.  Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activation. , 2010, Interactive cardiovascular and thoracic surgery.

[30]  C. Schlensak,et al.  Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart , 2010, Thrombosis and Haemostasis.

[31]  W. Kop,et al.  Prospective, observational study of antiplatelet and coagulation biomarkers as predictors of thromboembolic events after implantation of ventricular assist devices , 2009, Nature Clinical Practice Cardiovascular Medicine.

[32]  R. Hetzer,et al.  Alterations in coagulation after implantation of a pulsatile Novacor LVAD and the axial flow MicroMed DeBakey LVAD. , 2000, The Annals of thoracic surgery.

[33]  P. Teirstein,et al.  Dynamics of platelet functional recovery following a clopidogrel loading dose in healthy volunteers. , 2008, The American journal of cardiology.

[34]  A. Weyrich,et al.  Platelets: signaling cells in the immune continuum. , 2004, Trends in immunology.

[35]  R. Davidson,et al.  Description of an In Vitro Platelet Function Analyzer-PFA-100™ , 1995, Seminars in Thrombosis & Hemostasis.

[36]  Dong Chen,et al.  Comparative Analysis of von Willebrand Factor Profiles in Pulsatile and Continuous Left Ventricular Assist Device Recipients , 2010, ASAIO journal.