Note: COVER -- TITLE -- COPYRIGHT -- CONTENTS -- CONTRIBUTORS -- PREFACE -- GLOSSARY -- CHAPTER 1 THE STRUCTURE AND PRODUCTION OF BLOOD PLATELETS -- INTRODUCTION -- 1. THE STRUCTURE OF THE RESTING PLATELET -- The intracellular components of the resting platelet -- Granules -- Organelles -- Membrane systems -- Open canalicular system -- Dense tubular system -- The cytoskeleton of the resting platelet -- The marginal band of microtubules -- The actin cytoskeleton -- The spectrin membrane skeleton -- MEGAKARYOCYTE DEVELOPMENT AND PLATELET FORMATION -- Commitment to the megakaryocyte lineage -- Endomitosis -- Cytoplasmic maturation -- Platelet formation -- The cytoskeletal machine of platelet production -- Platelet formation in vivo -- Regulation of megakaryocyte development and platelet formation -- Apoptosis and platelet biogenesis -- THE STRUCTURE OF THE ACTIVATED PLATELET -- The platelet shape change -- Granule secretion -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 2 PLATELET IMMUNOLOGY: STRUCTURE, FUNCTIONS, AND POLYMORPHISMS OF MEMBRANE GLYCOPROTEINS -- INTRODUCTION -- THE GP Ib/IX/V COMPLEX -- Structure of the GP Ib/IX/V complex -- Signaling and functions of GP Ib/IX/V complex -- Polymorphisms of the GP Ib/IX/V Complex -- THE…NTEGRIN (GP IIb/IIIaCOMPLEX, CD41/CD61) -- Structure of the αIIbβ3 integrin -- Affinity regulation of the αIIbβ3 integrin -- Location of the ligand-binding site -- Location of epitopes for conformation-dependent mAbs -- Polymorphisms of the αIIbβ3 complex -- GP IIIa (β3 integrin) -- GP IIb(αIIb integrin) -- Clinical relevance and future directions -- α2β1 INTEGRIN (GP Ia/IIa) -- Structure of α2β1 integrin -- Signaling of α2β1 integrin -- Polymorphisms of the α2β1 complex -- GP Ia(α2 integrin) -- CD36 (GP IV, GP IIIb) -- CD36 Polymorphisms -- GP VI -- GP VI Polymorphisms -- FUTURE AVENUES OF RESEARCH -- REFERENCES. , CHAPTER 3 MECHANISMS OF PLATELET ACTIVATION -- INTRODUCTION -- THREE STAGES OF PLATELET PLUG FORMATION -- Stage I: The initiation of platelet activation -- Stage II: Extension of the hemostatic plug through recruitment of additional platelets -- G Protein-mediated signaling in platelets -- Platelet activation in vivo -- Gq and the activation of phospholipase Cβ -- Gq, G13, and the actin cytoskeleton -- Signaling through Gi family members -- ADP: Two receptors with distinguishable functions -- Thrombin: two receptors with overlapping functions -- Epinephrine: potentiator of other agonists -- Thromboxane A2: twin receptor(s) coupled to Gq and G12/13 -- Stage III: Perpetuation (stabilization) of the platelet plug -- Integrins, adhesion, and outside-in signaling -- Other adhesion molecules -- Receptor: ligand interactions at the platelet:platelet interface -- PROTEOMICS AND PLATELETS -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 4 PLATELET PRIMING -- INTRODUCTION -- EFFECT OF PLATELET PRIMERS IN VITRO -- Proteins -- Gas6 -- Factor VIII -- Matrix metalloproteinases -- MMP-1 -- MMP-2 -- Soluble CD40 ligand (sCD40L) -- Low-density lipoproteins (LDLs) -- CYTOKINES -- Vascular endothelial growth factor (VEGF) -- Thrombopoietin (TPO) -- Chemokines -- Leptin -- Hormones -- Estrogens -- Epinephrine -- Histamine -- Prostaglandins -- Prostaglandin E2 -- Ions -- Zinc -- Others -- Lipopolysaccharides (LPS) -- Foreign substances -- Succinate -- EFFECT OF PLATELET PRIMERS IN VIVO: EVIDENCE FROM ANIMAL STUDIES -- Proteins -- Gas6 -- Matrix metalloproteinase 2 (MMP-2) -- CD40L -- Cytokines -- Thrombopoietin -- Leptin -- Hormones -- Epinephrine -- Prostaglandins -- Prostaglandin E2 -- Others -- Lipopolysaccharides (LPS) -- Exogenous Substances -- EFFECT OF PLATELET PRIMERS IN VIVO: STUDIES IN HUMANS -- Proteins -- Cytokines -- Hormones -- Prostaglandins. , CONCLUSION -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 5 PLATELETS AND COAGULATION -- INTRODUCTION -- EFFECTS OF PLATELETS AND THEIR PRODUCTS ON COAGULATION -- Platelet products that enhance TF synthesis -- Platelet products that increase TF production -- PLATELET PROCOAGULANT ACTIVITY -- Overview of coagulation -- Exposure of phosphatidylserine -- Platelet microvesicles -- Alpha-granule proteins -- Defects in platelet procoagulant activity -- Platelet heterogeneity and coated platelets -- Platelets and TF -- Effect of platelet antagonists on procoagulant activity -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 6 VESSEL WALL-DERIVED SUBSTANCES AFFECTING PLATELETS -- INTRODUCTION -- Vascular endothelium -- Normal endothelial function -- Endothelial dysfunction -- Platelets -- Platelet activation and adhesion -- Platelet-endothelium interaction -- Platelet-endothelium interactions in thrombosis and hemostasis -- Platelet-endothelium interactions in inflammation -- ENDOTHELIUM-DERIVED SUBSTANCES THAT AFFECT PLATELETS -- Nitric oxide -- NO synthesis -- Effect of NO on platelet function -- Prostaglandins (PGs) -- PG synthesis -- Effect of PG on platelet function -- Ecto-ATPDase -- SURFACE-BOUND ENDOTHELIAL ANTIPLATELET FACTORS -- Platelet-endothelial cell adhesion molecule-1 (PECAM-1) -- ENDOTHELIUM, PLATELETS, AND VASCULAR DISEASE -- Mechanisms underlying endothelial dysfunction in vascular disease -- Endothelium-derived vasodilators -- Reactive oxygen species (ROS) -- Vascular disease -- Cardiovascular disease -- Hypertension -- Hypercholesterolemia -- Diabetes mellitus -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 7 PLATELET-LEUKOCYTE-ENDOTHELIUM CROSS TALK -- INTRODUCTION -- PLATELET-DERIVED INFLAMMATORY MEDIATORS -- Platelet-derived chemokines -- Platelet-derived cytokines and cytokine-like factors. , Platelet-derived adhesion proteins -- Platelet-derived coagulation factors -- Platelet-derived growth factors -- Platelet-derived eicosanoids and lipid mediators -- Platelet-derived proteases -- PLATELET-ENDOTHELIAL CELL CROSS TALK -- Platelet-endothelial cell adhesion -- Platelet-endothelial signaling, thrombosis, and inflammation -- PLATELET-LEUKOCYTE CROSS TALK -- Platelet-leukocyte adhesion -- Platelet-leukocyte signaling, thrombosis, and inflammation -- ANTI-INFLAMMATORY EFFECTS OF PLATELET INHIBITION -- COX inhibition, aspirin, and selective COX-2 inhibitors -- ADP-receptor (P2Y12) antagonists -- GP IIb/IIIa receptor antagonists -- Phosphodiesterase inhibitors -- CONCLUSIONS AND CLINICAL IMPLICATIONS -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 8 LABORATORY INVESTIGATION OF PLATELETS -- INTRODUCTION -- BLOOD SAMPLING -- TESTS OF PLATELET MORPHOLOGY -- Platelet count -- Platelet size and appearance -- Exercise and MPV -- Vascular disease -- TESTS OF GLOBAL PLATELET FUNCTION -- Bleeding time -- Rapid platelet function assay -- PLATELET AGGREGATION TESTS -- Optical (turbidometric) platelet aggregometry -- Sample preparation -- Advantages/limitations -- Agonist-induced platelet aggregation -- ADP -- Epinephrine -- Collagen -- Ristocetin -- Other platelet-aggregating agents -- VerifyNow® -- Impedance (whole-blood) platelet aggregometry -- Advantages/limitations -- Platelet activation under controlled shear conditions: PFA-100® -- Variables that influence the PFA-100® -- The PFA-100® versus the bleeding time -- Clinical utility -- Platelet function under flow -- FLOW CYTOMETRIC ASSESSMENT OF PLATELET FUNCTION -- Monoclonal antibodies -- Methodologic aspects -- Advantages/limitations -- SOLUBLE PLATELET ACTIVATION MARKERS -- Platelet granular contents (β-thromboglobulin and platelet factor 4) -- Glycoprotein V (GPV) -- sP-Selectin. , Platelet adhesion assay -- Miscellaneous -- URINARY MARKERS OF PLATELET FUNCTION -- Urinary TxA2 metabolites -- Urinary TxB2 -- IS THERE AN IDEAL WAY TO QUANTIFY PLATELET PATHOPHYSIOLOGY? -- NOVEL TECHNIQUES FOR THE STUDY OF PLATELETS/MKS -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 9 CLINICAL APPROACH TO THE BLEEDING PATIENT -- INTRODUCTION -- INITIAL URGENT MEASURES -- INSPECTION FOR SUBCUTANEOUS BLEEDING -- FOCUSED MEDICAL HISTORY AND GENERAL PHYSICAL EXAMINATION -- FURTHER DIFFERENTIAL DIAGNOSIS -- CONCLUSION -- FUTURE AVENUES OF RESEARCH -- REFERENCES -- CHAPTER 10 THROMBOCYTOPENIA -- INTRODUCTION -- IMMUNE THROMBOCYTOPENIC PURPURA -- Epidemiology and presentation -- Differential diagnosis -- Initial evaluation -- Pathogenesis and laboratory diagnosis -- Additional clinical features of ITP -- Clinical management -- Initial treatment -- Emergent treatment -- Management of first relapse: splenectomy and alternative medical treatments -- Chronic ITP: splenectomy failures -- Chronic, refractory ITP -- Immunosuppression -- Investigational approaches -- ITP IN CHILDHOOD -- Presentation -- Differential diagnosis -- Management at presentation -- Management of acute ITP after the first week -- Chronic ITP: management after 6 to 12 months -- INHERITED THROMBOCYTOPENIA -- Myelodysplasia (MDS) -- DRUG-INDUCED THROMBOCYTOPENIA -- NEONATAL THROMBOCYTOPENIAS -- FETAL AND NEONATAL ALLOIMMUNE THROMBOCTOPENIA -- Pathogenesis -- Clinical presentation -- Intracranial hemorrhage -- Predictors of disease -- Diagnosis -- SCREENING PROGRAMS -- Management -- Antenatal management -- Severity of disease -- Intracranial hemorrhage -- Therapeutic procedures -- Overall approach to therapy -- Specific management strategies -- Very high risk -- High risk -- Standard risk -- No well-defined risk -- Long-term effects of antenatal management on the treated fetus. , Treatment in the newborn.