Platelet Antagonists

Platelet antagonists play an important role in both primary and secondary prevention of atherothrombotic events. Despite their proven benefit, individual response (and protection) varies considerably, emphasizing the importance of developing monitoring tools (tested prospectively in clinical trials) that can better determine the degree of platelet inhibition that is both safe and effective. Platelet function studies were developed originally for the evaluation of patients with unexplained bleeding and have contributed greatly to the understanding, diagnosis, and management of hereditary abnormalities such as von Willebrand disease and Glanzmann’s thrombasthenia (platelet glycoprotein [GP] IIb/IIIa receptor deficiency). Although conventional platelet function studies (turbidimetric aggregometry) have technical limitations that preclude their routine use for gauging antithrombotic therapy, they may provide guidance when hemorrhagic complications arise and in determining pretreatment risk in individuals suspected of having an intrinsic platelet abnormality. The bleeding time, considered an indicator of primary hemostasis (platelet plug formation), is defined as the time between making a small standardized skin incision and the precise moment when bleeding stops. The test is performed with a template, through which the medial surface of the forearm is incised under 40 mmHg standard pressure. A normal bleeding time is between 6 and 10 minutes. Although considered a “standardized” test of platelet function, the bleeding time can be influenced by a variety of factors, including platelet count, qualitative abnormalities, and features intrinsic to the blood vessel wall (George and Shattil, 1991). Platelet adhesion is the initiating step in primary hemostasis. Although platelet binding is an important component of this process, there are many others, including blood flow rate, endothelial cell function, adhesive proteins, and the subendothelial matrix. The original test used for assessing adhesion, platelet retention, was based on adherence to glass bead columns. The current laboratory evaluation of platelet function is based predominantly on turbidimetric platelet aggregometry (also known as light transmission aggregometry). This test is performed by preparing platelet-rich plasma (with platelet-poor plasma as a control) and eliciting an aggregation response with adenosine diphosphate, epinephrine, collagen, arachidonic acid, and ristocetin (Born, 1962).