INTRODUCTION

Platelets evolved as a means of responding to injuries that produce holes in a high-pressure circulatory system and, to a great extent, the attributes acquired by platelets through evolution reflect the demands placed upon them. To be maximally useful and minimally harmful, circulating platelets must be able to sustain repeated contact with the normal vessel wall without premature activation, recognize the unique features of a damaged wall, cease their forward motion upon recognition of damage, adhere to the vessel wall despite the forces produced by continued blood flow, and stick (cohere) to each other, forming a stable plug of the correct size that can remain in place until it is no longer needed. Pathologic thrombus formation occurs when diseases or drugs subvert the mechanisms designed to allow platelets to respond as rapidly as possible to injury.

Although much has been discovered about the mechanisms that underlie normal platelet activation, a considerable amount still remains to be learned. Platelets have been the subject of fruitful investigation for most of the past 50 years. However, a number of technical breakthroughs within the past 10 years have moved the field along considerably. Among these are the widespread use of genetically modified mice, the availability of improved methods for studying platelet function in vitro and in vivo under flow conditions and in real time, a better understanding of signaling mechanisms in general, and the development of methods that allow megakaryocyte (MK) maturation and platelet formation to be studied ex vivo.