INHIBITION OF PLATELET-DEPENDENT THROMBOSIS BY LOCAL-DELIVERY OF HEPARIN WITH A HYDROGEL-COATED BALLOON

Background Systemic administration of heparin can decrease mortality a nd morbidity of acute ischemic coronary syndromes such as unstable ang ina and myocardial infarction. Hemorrhage is the major limiting factor in the clinical use of systemic heparin. The objective of the present study was to determine whether local delivery of heparin could inhibi t platelet-dependent thrombosis without altering systemic bleeding par ameters. Methods and Results Hydrogel-coated angioplasty balloon cathe ters were dipped in a heparin solution, dried, and applied to a platel et-rich mural thrombus in a chronic ex vivo porcine arteriovenous shun t. In-111-labeled platelet deposition was quantified by gamma camera i maging. In a separate series of experiments, H-3-heparin was used to e stimate the amount of heparin delivered to the thrombus with the coate d balloon. Systemic heparin administration produced a dose-dependent d ecrease in platelet-dependent thrombus formation that was maximal at 2 00 units/kg. Bleeding times and activated partial thromboplastin times were prolonged at this dose. An equal inhibition of thrombus formatio n was achieved after the coated balloon was dipped in a heparin soluti on (10 000 units/mL) and deployed at the mural thrombus. In contrast t o systemic heparin administration, there was no alteration in bleeding parameters associated with local heparin delivery. The estimated amou nt of heparin delivered with the coated balloon was 40 units. Conclusi ons Local delivery of heparin in amounts sufficient to inhibit platele t-dependent thrombosis can be accomplished with a hydrogel-coated coro nary angioplasty balloon catheter. Local heparin delivery can inhibit thrombus formation in amounts that are several orders of magnitude low er than the required systemic dose. Local delivery of heparin was not associated with prolongation of bleeding parameters.