Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices

Artif Organs. 2008 Oct;32(10):792-9. doi: 10.1111/j.1525-1594.2008.00632.x.

Abstract

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.

MeSH terms

  • Adsorption
  • Blood Platelets / cytology
  • Blood Platelets / drug effects
  • Delayed-Action Preparations / pharmacology
  • Fibrinogen / drug effects
  • Fibrinogen / metabolism
  • Guanidines / pharmacology*
  • Heart-Assist Devices*
  • Hemorheology
  • Humans
  • Platelet Adhesiveness / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Pyrazines / pharmacology*

Substances

  • Delayed-Action Preparations
  • Guanidines
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Pyrazines
  • Fibrinogen
  • TAK 029