Extensive contact between blood and the synthetic surfaces of an extra-corporeal circuit causes thrombocytopenia, release of platelet granular contents, initiation of thromboxane synthesis, disruption of subcellular architecture and loss of platelet sensitivity to standard platelet agonists. All too frequently, these adverse platelet alterations are reflected in a prolongation of the post-operative bleeding time and excessive blood loss which precludes implementation of long-term circulatory assist devices. Unfortunately, a truly biocompatible material does not exist and efficiency of gas transport demands haemodynamic designs which actually promote platelet injury. Although manipulation of surface properties and mechanical improvements in circuitry have managed to reduce platelet-surface interactions, the ultimate potential of these manoeuvres may be limited. Synthetic surfaces and soluble agonists, however, appear to modulate similar pathways suggesting that temporary platelet inhibition might provide significant protection by preserving the morphological and functional integrity of circulating platelets during contact with extracorporeal circuits.