Heparin-like effect of a dual antiplatelet and anticoagulant (APAC) agent on red blood cell deformability and aggregation in an experimental model

Abstract

Treatments with different antithrombotic agents can affect micro-rheological variables, such as red blood cell (RBC) deformability and aggregation. Since the effect of dual antiplatelet and anticoagulant (APAC) treatment on micro-rheology is unknown, we aimed to investigate the effect of different intravenous doses of APAC on hematological and micro-rheological variables in a porcine model. Two groups were formed (APAC group, Control group), and blood was collected from the animals at preset intervals. Hematological variables, RBC deformability, and aggregation were measured. We observed an improvement in the RBC deformability measured at a low shear stress range (< 3 Pa). However, after both doses, a decrease in the maximal elongation index of RBC values occurred in the APAC group. RBC aggregation increased after APAC bolus dose, while it gradually and dose-dependently decreased. Supposedly, the improvement in RBC deformability that was observed at a lower shear rate could facilitate aggregation. Administration of APAC and unfractionated heparin (UFH) caused comparable changes in hematological and hemorheological variables. Signs of thrombosis or bleeding did not occur. APAC and UFH had comparable micro-rheological effects.

Keywords: Anticoagulant; Antiplatelet; Hemorheology; Red blood cell aggregation; Red blood cell deformability.

Fig. 1

Sampling times and intravenous bolus administration times in the Control group (n = 5) (a) and APAC group (n = 5) (b). Times of administration of the different bolus doses of UFH and APAC and blood sampling in the UFH group (n = 5) (c) and APAC group (n = 5) (d). Open arrow refers to vehicle (1 mL of 137 mM NaCl and 10 mM Na₂HPO₄, pH: 7.5), hatched arrow to APAC, black arrow refers to blood sampling, lined arrow to protamine sulphate and grey arrow to UFH

Fig. 2

Elongation index in the function of shear stress in Control group (a) (n = 5) and APAC group (b) (n = 5) blood samples. Aggregation index (AI [%]) values measured after disaggregation (c). Blood sampling times (1) 5 min after administration of the vehicle; (2) 15 min after the first dose; (3) 75 min after the first dose; (4) 15 min after the second dose; (5) 30 min after the second dose; (6) 75 min after the second dose; (7) 15 min after the third dose; (8) 15 min after protamine sulphate

Fig. 3

Elongation index in the function of shear stress (Pa) in UFH group (a) (n = 5) and APAC group (b) (n = 5) blood samples. Aggregation index (AI [%]) values measured after disaggregation (c)