CARD29: Sodium Bicarbonate as an Adjunctive Local Anti-Thrombotic Agent for Cardiovascular Therapeutic Devices

Abstract

Purpose: Despite clinical efficacy, mechanical circulatory support (MCS) systems remain challenged in maintaining physiologic hemostatic balance. The Impella heart pump is a micro-axial percutaneous MCS device that utilizes a purge flow for maintaining bearing lubrication, purge patency, and anti-thrombosis purposes, forming a purge gap micro-environment wherein purge fluid and blood may mix. During operation, a continuous 5% dextrose in water (D5W) + heparin purge solution flows through the Impella catheter to inhibit protein adsorption and thrombosis in internal purge gaps. This exogenous heparin can increase bleeding risk and complicate systemic heparin and anticoagulation management. Recent FDA approval has made available sodium bicarbonate (SB) as an alternative to purge heparin. Despite promising early clinical results, the influence of SB on blood platelets, central mediators of thrombosis and bleeding, remains unclear. Here, we investigated the effect of SB on human platelet function (adhesion, aggregation, activation) in vitro following incubation with relevant concentrations of heparin or SB. Methods: Human gel-filtered platelets (20,000/µL) or platelet rich plasma (100,000/µL) were obtained from ACD-A anticoagulated whole blood. Platelets were incubated (6:4 platelets: purge) at 37°C for 15 min with purge solutions (D5W; 50U/mL heparin + D5W; 25mEq/L SB + D5W; 50mEq/L SB + D5W; 100mEq/L SB + D5W). Platelet activation was measured as thrombin generation rate utilizing a previously-described modified prothrombinase assay. Platelet adhesion was measured via imaging (Nikon DS-Qi2; 100X) of fluorescent-labelled platelets (BioTracker490) adhered to glass. Platelet aggregation was quantified from agonist-mediated aggregation using a light-transmission aggregometer (PAP8E). All experiments were performed in duplicate with N≥3 donors. Results: SB altered overall platelet function in a concentration-dependent manner. 100mEq/L SB led to a significant decrease in platelet adhesion (0.11% decrease; Fig 1A), whereas only 25mEq/L SB led to a significant reduction in thrombin generation rate (14.0% decrease; Fig 1B). Collagen-mediated aggregation was significantly reduced after addition of 100mEq/L SB (42.2% decrease; Fig 1C). Traditional D5W+heparin solution significantly reduced platelet function, in all categories, to a greater degree than 25mEq/L SB, but had a similar effect to 50 or 100mEq/L SB when comparing platelet adhesion and activation metrics. Conclusion: SB in the concentrations tested led to altered platelet function, modulating surface adhesion, activation, and collagen-mediated aggregation –useful effects to limit device fouling and purge gap thrombosis. Use of SB as a localized anti-thrombotic agent, where its concentration and effect are not rapidly diluted, is promising for MCS such as the Impella system. SB use offers the potential for locally limiting thrombogenicity at the purge gap, while avoiding the need for exogenous heparin.