Sodium Bicarbonate Effect on Platelet Function and Whole Blood Clotting at the Point-of-Care

Abstract

In the human body, bleeding and blood clotting maintain a delicate balance, particularly during the use of short- and long-term blood contacting medical devices. The management of bleeding and clotting poses a significant challenge for clinicians dealing with medical devices, as their use often necessitates a balance between preventing thrombosis and avoiding hemorrhagic complications. This delicate balance requires careful monitoring of anticoagulant therapy and timely intervention to address bleeding or clotting events that may arise. Furthermore, factors such as patient comorbidities, drug sensitivities (particularly to heparin), and procedural complexity can further complicate management strategies. Platelets are a central element in thrombus formation and coagulation, however, there are currently no rapid and user-friendly and portable point-of-care devices available for assessment of platelet function in patients requiring therapeutic interventions. As such, alternatives to heparin therapy and methods of rapid and accurate measurement of platelet function for anticoagulation management are two areas of unmet needs in cardiovascular therapy. This study investigated the interaction between sodium bicarbonate, as an alternative to heparin, on whole blood and platelets, aiming to understand how to preserve the balance between bleeding and blood clotting amidst medical interventions. Furthermore, we herein describe utilizing a prototypic impedance aggregometer, the Microfluidic Electrical Impedance (MICELI) for point-of-care platelet function analysis. The MICELI was validated with biostable “lyosphere” compared to the liquid form of thrombin receptor activator peptide 6 (TRAP-6) for improved storage and ease-of-use; the MICELI was further employed to evaluate sodium bicarbonate’s influence on TRAP-6-mediated platelet function. Sodium bicarbonate efficacy was also addressed utilizing standard whole blood clotting time assays. We hypothesized that sodium bicarbonate would lead to significant changes in clotting parameters and platelet aggregation and we hypothesized that platelet aggregation parameters would remain the same between agonist-containing lyospheres and standard liquid agonist (TRAP-6). Each experiment was performed in duplicate from N ≥ 5 human donors to provide statistically significant insights into thrombosis and hemostasis management.