Procoagulant Activity of Adherent Platelets

........................................................................................................................ 9 INTRODUCTION ............................................................................................................... 11 REVIEW OF THE LITERATURE ...................................................................................... 13 1. Platelets ........................................................................................................................... 13 1.1. Morphology ............................................................................................................ 13 Platelet surface ....................................................................................................... 13 Platelet membranous system .................................................................................. 14 Cytoskeleton ........................................................................................................... 14 Secretory granules .................................................................................................. 14 Regulation of intracellular calcium ........................................................................ 15 1.2. Adhesive platelet receptors ..................................................................................... 16 GPIb/IX/V .............................................................................................................. 16 Collagen receptors .................................................................................................. 17 GPIa/IIa .......................................................................................................... 18 GPVI ............................................................................................................... 19 GPIIb/IIIa ............................................................................................................... 21 Additional receptors related to adhesion ................................................................ 22 1.3. Platelet receptors for soluble agonists .................................................................... 23 Thrombin receptors ................................................................................................ 23 ADP receptors ......................................................................................................... 23 Receptors for other soluble agonists ....................................................................... 24 2. Coagulation ..................................................................................................................... 24 2.1. Initiation of coagulation .......................................................................................... 25 2.2. Propagation of coagulation ..................................................................................... 26 2.3. Intrinsic pathway of coagulation ............................................................................. 26 2.4. Termination of coagulation ..................................................................................... 27 3. Platelet function in hemostasis and thrombosis .............................................................. 28 3.1. Adhesion, aggregation and secretion ...................................................................... 28 3.2. Physiologic inhibition of platelet activation ........................................................... 28 3.3. Platelet procoagulant activity .................................................................................. 29 Membrane phospholipids ....................................................................................... 29 Generation of microparticles .................................................................................. 29 Platelet procoagulant agonists ................................................................................ 29 Procoagulant activity of platelets in plasma ........................................................... 30 Platelet receptors for coagulation factors ............................................................... 31 Platelet-derived coagulation factors ....................................................................... 32 4. Effects of antiplatelet agents on platelet procoagulant activity (PCA) ........................... 33 4.1. Aspirin, dipyridamole and clopidogrel ................................................................... 33 4.2. Glycoprotein IIb/IIIa antagonists ............................................................................ 33 Abciximab .............................................................................................................. 34 Tirofi ban ................................................................................................................. 34 Eptifi batide ............................................................................................................. 34 Clinical effi cacy ...................................................................................................... 35 Oral GPIIb/IIIa antagonists .................................................................................... 36 Parenteral GPIIb/IIIa antagonists and platelet procoagulant activity ..................... 36