Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices.
Shear-induced platelet activation (SIPA) has been identified to induce platelet adhesion and thrombus formation in continuous flow left ventricular assist devices (LVAD). Platelet glycoprotein (GP) IIb/IIIa receptor inhibitors are effective to prevent SIPA. However, systemic GP IIb/IIIa receptor inhibitor application is associated with severe bleeding complications. The aim of the study was to evaluate (i) the feasibility of absorption and elution of the GP IIb/IIIa receptor blocker TAK-029 from the Ti6Al4V surface of the pump; and (ii) the effect of local GP IIb/IIIa receptor blocker delivery regarding platelet adhesion on the surface of a continuous flow VAD model. Saturating concentrations of TAK-029 were adsorbed on the surface of a centrifugal pump. Whole human blood was perfused in circulatory mock loops using untreated (control), albumin-coated, or TAK-029-coated pumps. Peripheral resistance of the circulatory systems were adjusted accordingly to generate 5 L flow per min with impeller rotational speeds of 3500 (high-shear group) and 1500 rpm (low-shear group), respectively. Platelet adhesions on the respective impellers were quantified by ELISA and scanning electron microscopy (SEM). TAK-029 elution and half-life time were determined by ELISA. Compared with control, albumin-coated pumps showed 64 and 20% less platelet adhesions in the high- and low-shear group, respectively. TAK-029 coated pumps reduced platelet adhesion by additional 33 and 65%, respectively, compared with the albumin group. Elution of TAK 029 was initially very rapid and continued slowly. The results show that it is possible to adsorb and elute a small molecular weight GP IIb/IIIa receptor blocker from the pump surface. This drug elution reduced platelet adhesion on the pump significantly. Further studies are necessary to find a suitable drug bonding that will prolong the antiplatelet effect and preclude any bleeding complication caused by this procedure.
Linneweber
Joerg
J
Klinik für kardiovaskuläre Chirurgie, Charité-Universitätsmedizin Berlin, Germany. joerg.linneweber@charite.de
Dohmen
Pascal M
PM
Kertzscher
Ullrich
U
Affeld
Klaus
K
Konertz
Wolfgang
W
D000327:Adsorption; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000494:pharmacology; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D006353:Heart-Assist Devices; D018056:Hemorheology; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D006146:Guanidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011719:Pyrazines; D005340:Fibrinogen; C099142:TAK 029