Antithrombotic therapy for vascular prosthesis: an experimental model testing platelet inhibitory drugs

Abstract

Although Dacron vascular grafts are widely used, they are thrombogenic and rapid blood flow maintains patency. When blood flow is suboptimal, antithrombotic therapy may prevent early occlusion. We evaluated the effect of three platelet inhibitory drugs: acetylsalicylic acid (ASA), dipyridamole (DPM), sulphinpyrazone (SPZ), and a combination of ASA plus DPM on platelet adherence to woven Dacron in an artificial circulation. Heparinized blood from 18 volunteers was divided equally for test and control circuits, and to the test each drug was added in therapeutic concentration. The experiment was repeated ex vivo using blood donated by six volunteers after each had taken, separately for 1 week: (1) no drug; (2) ASA, 300 mg, three times a day; (3) DPM, 100 mg, four times a day; (4) SPZ, 200 mg, four times a day; (5) ASA, 300 mg, plus DPM, 75 mg, combined, three times a day. Platelet count, adhesion and aggregation were measured during the 60-minute perfusion, and scanning electron miscroscopy of the graft's luminal surface was performed. ASA was the most effective single agent, significantly impairing platelet function and reducing consumption of platelets by the graft. DPM reduced platelet adherence only in the ex vivo experiment, and its addition to ASA imparted no further influence. Sulphinpyrazone had little effect in either experiment. Antithrombotic therapy with ASA and DPM requires clinical evaluation.