Left Ventricular Assist Device Induced Coagulation and Platelet Activation and Effect of the Current Anticoagulant Therapy Regimen

Abstract ²²⁷¹

Left ventricular assist devices (LVADs) are mechanical pumps used to enhance cardiac function in heart failure patients. Platelet and coagulation activation was quantified to identify if the platelet and clot inhibiting drug regimen is effective in the LVAD patients. Seven patients with implanted LVADs were evaluated monthly for 3 months; 5 healthy adults and 5 patients on warfarin with normal cardiac output served as controls. All subjects signed an informed consent document prior to inclusion in the study. Freshly collected blood was assayed by the following: Plateletworks platelet aggregation (PWs; Helena; Beaumont, TX); PlateletMapping whole blood coagulation and platelet activity (PM; Haemoscope; Niles, IL); and flow cytometry platelet P-selectin upregulation and GPIIb/IIIa receptor activation. All assays used arachidonic acid (AA), ADP, collagen, and thrombin associated receptor activated peptide (TRAP) platelet agonists. In addition, von Willebrand factor (vWF) antigenic levels (Zymutest; Hyphen Biomed, France) were evaluated on frozen stored citrated plasmas. PWs showed a greater inhibition of collagen (31.8 vs 7.1% inh; p=0.008) and AA (30.8 vs 8.2% inh; p=0.002) induced platelet aggregation in patients; ADP induced platelet aggregation was not different between groups (10.8 vs 6.1% inh; p=0.711). PM showed an inhibition trend of AA (36.8 vs 25.1% inh; p=0.491) and ADP (36.2 vs 15.4% inh; p=0.056) mediated coagulation/platelet activation but a greater maximum amplitude of the blood clot in patients compared to normals (69.1 vs 64.9 mm; p=0.012). PM showed no significant inhibition of coagulation (R p=0.719; K p=0.569; angle p=0.430). In patients more than normals, flow cytometry showed an inhibition trend of platelet activation induced by AA (P-selectin: 24.2 vs 31.3% (+), p=0.064; GPIIb/IIIa: 16.8 vs 20.6% (+), p=0.052) and collagen (GPIIb/IIIa: 15.7 vs 29.7% (+), p=0.004); however a similar P-selectin expression to collagen and P-selectin and GPIIb/IIIa receptors to ADP and TRAP agonists was observed. There was no difference in any platelet or coagulation function parameter over the 3 months. The vWF levels, although remaining within the normal range, tended to increase during the 3 month period in the LVAD patients (from 97.9 ± 16.0% to 111.2 ± 18.2% at 1 month and to 113.9 ± 17.4% at 3 months; normals 106.5 ± 11.2%). This study shows that coagulation and platelet activation caused by the LVAD pump and generated shear forces is suppressed only to a limited degree by 81 mg/day aspirin and the anticoagulant effect of 1.8 INR warfarin is not robust. Modifications of the anticoagulant therapy regimen may improve upon the procoagulant effect generated by the LVAD pump. Using such assays as those described could facilitate determination of an optimal dosing strategy, as well as include consideration to avoid any potential increase in risk of bleeding.