BLOOD-CONTACTING MEDICAL DEVICES, THE DOUBLE EDGED SWORD BETWEEN THROMBOSIS AND BLEEDING
David Bark Jr.
Colorado State University, USA University of Colorado Anschutz Medical Campus
Cardiovascular disease remains the leading cause of death in industrialised nations and is becoming an increasing problem in developing countries. Common interventions involve blood-contacting medical devices, which are at high risk for catastrophic failure through thrombosis (blood clots). To mitigate this risk, anticoagulant and antiplatelet drug regimens are coadministered. However, systemic anticoagulation can induce bleeding and exhibits limited efficacy, making it the leading cause of drug-related deaths from adverse clinical events in the United States. As an alternative to drugs, device designs can be altered. In this regard, thrombosis occurring on devices can result from 1) blood-material interactions and/or 2) blood-hemodynamic responses. New biomaterials are being developed in attempts to reduce blood-material interactions. However, blood components are also highly sensitive to a changing haemodynamic (blood flow) environment, especially pathophysiological environments found in medical devices. Yet, the precise response of platelets (primary instigator of thrombosis) remains poorly understand since activating platelets and lysing erythrocytes release soluble activation agonists, creating a feedforward loop supporting further platelet activation. Also, only recently, it was also demonstrated that platelets and plasma proteins respond to shear stress gradients involving elongational flow independently of shear stress magnitude. Furthermore, it is increasingly clear that thrombo-inflammatory responses involve heterotypic platelet-leukocyte interactions that are also highly dependent on the haemodynamic environment. Therefore, blood damage models are often overly simplified. In this work, we utilized microfluidics to simplify fluid dynamics and to isolate specific hemodynamic characteristics of devices. We show that platelets actively respond to changes in the flow environment, independent of soluble activation agonists, and that late stages of platelet activation lead to a haemodynamic-dependent pro-inflammatory environment. Perhaps, paradoxically, we also show that flow characteristics of devices can enhance bleeding risk. Understanding the relationship between flow and blood responses will allow better bloodcontacting medical device design.