THROMBOGENESIS IN BLOOD PUMPING DEVICES

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The risk of thrombosis and thromboembolization remains a major postimplant concern with all devices that contact blood. Attempts to control thromboembolism with drugs are not always successful because the thromboembolic process involves a number of factors, many of which are not well understood. Contributing factors include the device design and resulting flow patterns, the materials used, and the coagulation state of the blood. A major problem with device-associated thromboembolization is the lack of available methods to monitor the course of thromboembolic events in real time. Currently, treatments are based on clinical experience and the circulating levels of fibrin degradation products; the latter appear in blood only after thrombosis has occurred. Proper use of anticoagulants/antiplatelet agents is critical for successful postimplant patient management; using inadequate amounts fails to control thrombosis, and using excessive amounts leads to bleeding, a frequent postimplant problem. Real-time detection of thromboemboli would make it possible to adjust the dose of antithrombotic agents to the most effective level, thus greatly facilitating proper patient management. It would also make it possible to directly evaluate therapeutic strategies for controlling device-related thromboembolism. With the help of a laser light-scattering device that can detect microemboli in circulating blood in real time and a blood-filtration method to assess microemboli occlusiveness, the applicants have demonstrated the feasibility of microemboli detection in blood pumps in an ex-vivo animal model. They have noted that microemboli are released immediately after a device comes in contact with circulating blood. Initially, the emboli released are minimally-occlusive, but the emboli released later in the time course of blood-material contact are more occlusive, even though the number of emboli released may decrease. The presence of therapeutic concentrations of heparin during initial blood- material contact fails to stop the embolic process. Whether the device exhibits decreasing embolization over the next several hours (perhaps due to surface passivation) or continues to be thrombogenic appears to depend on the device design (the presence of areas of stases or other flow disturbances) and surface-related blood-material interactions. The applicants propose to employ a set of tools capable of directly monitoring thromboemboli to investigate thrombogenesis in blood pumps under clinically-relevant conditions and to evaluate the effectiveness of various available approaches to minimize (or prevent) thrombogenesis. After completing important in-vitro calibration studies, they will use a calf ex-vivo LVAD model to determine the antithromboembolic effectiveness of three commonly-used antithrombotic pharmacologic agents - heparin, aspirin with heparin, and coumadin - and one commonly-used - The results will provide important and immediate clinical benefits in post-implant patient management and will contribute to the understanding of thromboembolism to aid long-term development of blood-contacting devices.