Manual of Blood Platelets: Morphology, Physiology and Pharmacology Gundu HR Rao
Page numbers followed by f refer to figure, t refer to table.
Abciximab 81, 82, 113, 142
Acetyl salicylic acid 106, 142
Acetylates COX enzymes 106
Adenosine 91, 126, 140, 184
diphosphate 15, 37, 40, 47, 102, 120, 149, 152f, 155f, 167, 183
receptor antagonists 88
triphosphate 42, 155f
Adenylyl cyclase, stimulators of 78, 88, 91
Adhesive molecule 121
Advance glycation end products 124
Alpha granules 3f
Amino acids 193
Angel-wing closure device 182f
Angina 143
unstable 91, 143
Angioplasty 143
Angiotensin-converting enzyme inhibitors 113
Annular perfusion
chamber 171f
devices 181
Anticancer molecules, targeted delivery of 196f
Antiplatelet drugs 79f, 91
clinical trials of 93
development of 90
pharmacology of 77, 91f
Antiplatelet therapies 88, 90
Aortic prostaglandins 32
Arachidonate 151, 154f
insensitive platelets 151
sensitive platelets 151
Arachidonic acid 20, 60, 91, 93, 102, 121, 150, 153, 167
metabolism 61f, 63f, 88, 102, 121, 122f
second messengers of 63f
response of 151
Arginine-glycine 169, 193
Arrhythmia, symptomatic cardiac 160
Arterial bypass surgery 143
Arterial disease, peripheral 91, 93, 106
Arterial thrombotic event, trigger of 123
Arterioles 166
Aspartic acid 169, 193
Aspirin 79, 88, 91, 94, 101, 106, 114, 142, 143, 190
clinical use of 103
mechanism of action of 106f
mediated inhibition of COX enzymes 64f
resistance 101, 106, 113
prevalence of 108
response units 111
Atherogenesis 121
Atherosclerosis 88, 101, 120
Atomic force microscopy 12, 13f
Average lumen diameter 167
Balloon catheter for blood compatibility, screening of 171f
Baumgartner perfusion chamber 170f
Benzoic acid 114
Benzydamine 91
Bernard-Soulier syndrome 29
Bileaflet heart valve 182f
Bleeding diathesis 41
Blood 14
biocompatibility studies 179
biomaterial interactions 194
validation of 185
cells 128
clot studies 180
components 128
role of 88
perfusion system 187
platelets 36, 70, 89, 120, 138
pressure 96
urea nitrogen 191
vessels, inflammatory disease of 88
Body mass index 89
Bovine platelet 31, 31f
Caffeine 79
antagonists 88, 91
chelators 91
in platelet activation, role of 55
ionophore 70
mobilization 72f
modulation 70
Capillaries, microembolization of 123
Carbenicillin 32
Carboxylate 80f
Cardiovascular disease 65, 77, 90
Cardiovascular drug delivery 195
Carotid endarterectomy 91
discoid 8
matrix components 174f
membranes 3f
Cell-cell interaction 22, 37f, 184
Cellular calcium homeostasis 89f
Ceramide-I-phosphate 49
artery disease 77
ischemia 106
Cerebrovascular disease 77, 91, 106
Chandler loop system 184f
Chediak-Higashi syndrome 24, 25, 27
Chlorpromazine 32
Chlortetracycline 56
Cholesterol 4, 137
Circulating blood cells and inflammation, activation of 139
Cirrhosis 22
Citrate, mixture of 184
Clopidogrel 79, 92, 94, 114
Coleonol 91
Collagen 39, 46
microfibrils 169f
Conventional electron microscopy 12
Coronary artery
graft 95
surgery 109
disease 77, 90, 91, 101, 120, 137, 158, 169
Coronary syndrome, acute 95, 101, 137, 160
Coumadin 190
C-reactive protein 88, 122, 138
Cross-eyed platelet 3f
Cyclic adenosine monophosphate 71, 114
Cyclic guanosine monophosphate 71, 149
Cyclic heptapeptide 82
Cyclic nucleotides 70
Cyclooxygenase 29, 71, 79, 101, 121, 138
deficiency 29, 154f
derived endothelium-dependent constriction factor 126, 168
inhibitors 78, 80f, 91
Cytosolic calcium 56
Dazoxiben 79
Dengue virus 22
Dense tubular system 2f, 3f, 5, 43, 55
Diabetes 88, 106, 120
mellitus 120, 124
pathogenesis of 128
Diabetic retinopathy 129
Diacylglycerol 58
Diamide 125
Didodecyldimethylammonium bromide 196
Dipyridamole 79, 184
Docosahexaenoic acid 65
Dog platelets 66f
nonresponsive 151
Drug-eluting stent 95
Dual antiplatelet therapy 94
Ectophosphatase 50
Eicosanoid 60, 64
metabolism 60
synthesis 60f
Electron microscopy 3f, 12
Elevated blood phosphorus 88, 138
Endoperoxides 30, 38, 102
Endoplasmic reticulum 5, 62
Endothelial cells 11, 65, 166f, 168f
monolayer of 11f, 166
vascular 126, 138
Endothelial dysfunction 88, 130
Endothelium 168f
dependent constriction factor, hypoxia-induced 140, 168
nonreactive 11f
vascular 11
Enzyme-linked immunosorbent assay 41, 185
Epinephrine 66f, 102, 151, 153, 154f, 167, 183
Eptifibatide 82
Estrogen 141
Ethylenediaminetetraacetic acid 19, 56, 80, 110
European Society of Cardiology 114
Extracellular matrix 7, 173
Fatty acid
polyunsaturated 61
synthetase 90
Fenoprofen 91
Ferrous iron
chelators 62
postulated model for interaction of 80f
Fibrinogen 4, 9, 39
internalization of 17f
Fibrinopeptide A 105
Fibronectin 4, 9, 39, 46
Fixed drug combinations 113
Flow cytometry 181
Fluorescence microscopy 14f
Flurbiprofen 91
Forskolin 91
Framingham study 141
Furosemide 32
Giant granule 27, 27f
Glanzmann thrombasthenia 22, 25
Glycogen 3f
Glycoprotein 40, 79, 88
domains 2f
Glycosaminoglycan 7
G-protein, agonist-mediated activation of 48f
Granule mobilization 15f, 18
Gray platelet syndrome 24, 25, 28, 28f, 56
Guanylyl cyclase 91
stimulators of 78, 88
Heart 141
disease 77, 88
coronary 106
failure, end-stage congestive 190f
valves 188
Heartmate pumps 190f
Hematological parameters, management of 129
Heme-indomethacin interaction, model for 81f
Hemolytic-uremic syndrome 22
Hemorrhagic disease 1
Heparin 22
Heptadecatrienoic acid 32
Hereditary intrinsic platelet disorders 22
Hermansky-Pudlak syndrome 24, 25, 26f, 56, 73
High-resolution atomic force microscopy 14f
Hormone 140
replacement therapy 137
Horse platelets 31
Hyperfunction 22
Hyperglobulinemia 32
Hyperglycemia 123, 130
mediated reactive oxygen 125
Hypertension 88, 120
pathogenesis of 120
Ibuprofen 79, 88, 91
Imidazole congeners 91
Immune thrombocytopenia 22
Incontinence, device for management of 182f
Indomethacin 79, 80f, 91
amide groups of 80f
phospholipid 56
trisphosphate 89
Ionized calcium, modulation of 55f
Ketanserin 79
Laminins 9, 39, 46
Left ventricular-assist devices 189
Leukotrienes 60
Lidocaine 32
Lipid phosphate phosphatases and platelet activation 49
high-density 88, 137
low-density 124, 138
Lipoxins 60
Low-molecular-weight heparin 83
Lysophosphatic acid 49
Macroglobulinemia 22
Megakaryocytes 1, 36
Membrane modulation, mechanism of 106, 149
Membrane system 5
Metabolic disorder, chronic 128
Microangiopathic hemolytic anemia 22
Mitochondria 2f
Monitoring antiplatelet therapies 143
Monitoring antithrombotic therapies 143
Multifactorial disease 138
Multiple myeloma 22, 32
Muscular arteries 167
Myocardial infarction 106, 137, 158
acute 91, 122
Myosin light chain 57, 127
phosphorylation of 152
Naproxen 91
Nephropathy 129
N-ethylmaleimide 125
Neuropathy 129
Nitric oxide 91, 126, 140
Nitroblue tetrazolium 80
Nitroglycerine 91
Nitroprusside 91
Noncommunicable disease 77
Noradrenaline 157
Nucleic acids 64
Obesity 130
Omega-3 fatty acids 114
Open canalicular system 2f, 5, 13, 43
Oxidative stress 124, 130
Parallel perfusion devices 181
Penicillin 32
Percutaneous coronary interventions 39, 92, 194
Peripheral venous disease 91
Phentolamine 32
Phenylbutazone 91
Phorbol myristate acetate 14, 46
Phosphatidic acid 49
Phosphatidyl inositol 4,5 bisphosphate, hydrolysis of 89
Phosphatidylcholine 4, 60
Phosphatidylethanolamine 4, 60
Phosphatidylinositol 4, 60, 61f, 89f
Phosphatidylserine 4
Phosphodiesterase 79
inhibitors 78
Phosphoinositide metabolism and platelet activation 49
Phospholipase 51, 156
C 39, 49f, 51f
activation of 71
D 49
Phospholipids 61
Phosphoprotein, vasodilator-stimulated 40, 73
Plasma membrane 55
Plasminogen activator inhibitor 123, 168f
Platelet 3f, 7, 36, 36f, 37f, 72f, 180
activating factor 15, 51, 79, 149, 168f
activation 37f, 39, 46, 50
and inactivation 58f
mechanisms 46
adhesion 79, 192
aggregation 50f, 72f, 181
and signaling pathways 79
studies 15
aggregometry studies 14
agonist-mediated stimulation of 138
biochemistry 18
circulate 7
cyclooxygenases 93
cytoskeleton 9f
dense tubular system 79
derived microparticles 123
disaggregation 50f, 72f
discoid 3f, 7f, 12f, 13f, 36f, 166f
disorders 25
acquired 32
common 24
dysfunction 120
in animal platelets 30
feeling surface 7f
fibrin filaments 17f
from giant microbes 3t
function 60, 183
analyzer 144
assay 109
miscellaneous dysfunction of 29
testing system 180
glycoprotein inhibitors 82
high-resolution scanning electron microscopy 13f
hyperfunction 88, 120, 121, 123, 124, 130, 137
risks of 137
hypersensitivity of 124
in blood, role of 183
in vascular pathology, role of 128
interaction 174f
on rabbit aorta 173f
with injured vessel wall 46f
with membrane filters 179
with subendothelium 172
associated integrin 2f
glycoprotein receptors 38
modulation 149
microparticles 88
microthrombi on collagen surface 169f
morphology and
dysfunction 22
function 7
of Glanzmann thrombasthenia 23f
on collagen fibrils 11f
physiology 36, 89, 102, 120, 138, 167, 183
poor plasma 170
production 22
reaction time 174
device, occluder for 182f
monitoring device 174f
testing 95f
reaggregation 50f, 72f
research laboratory 11
responses 8
rich plasma 30, 150, 170
spreading 37f, 173f
stimulates phospholipase C, agonist-mediated activation of 102
structure and activation mechanisms 47f
surface interactions 17f
fluorescent imaging of 169f
on subendothelium 169f
thrombus 10f
ultrastructure 2f
morphology 1
vessel wall interactions 166
with dense bodies 26f
Polylactic polyglycolic acid copolymer 196
Preexisting vascular lesions, local progression of 123
Progestin replacement therapy 141
Prostacyclin 62, 126, 140, 151, 152
Prostaglandin 38, 60, 64, 102
intermediates 40
thromboxanes and prostacyclin 123
metabolism 151
Prostate-specific membrane antigen 197
Protease-activated receptor 38
Protein 64
kinase C 14, 48, 61
phosphorylations 50
Proteoglycans 7, 9
Prothrombotic coagulation pathways 130
Pulmonary hemorrhage, exercise-induced 31
Pyrolytic carbon 187, 188
bileaflet heart valves 185
leaflets, mechanical 187
Red blood cell 36f, 138
Refractory platelets 152f
Retinopathy 129
Salicylic acid 81
Scanning electron microscopy 3f, 12, 12f
Scott syndrome 25
Screening valves, customized chamber for 187f
Serine protease inhibitors 78
Serotonin 79
Sheep vesicular glands 71
Signal transduction
mechanism 58f
pathways 61f
Signaling via phospholipase
C pathway 51f
D pathway 52f
Small vessel disease 91
Smooth muscle cell proliferation 195
Sphingosine 1-phosphate 49
Spread platelets, detergent-insoluble cytoskeleton of 42f
Storage pool
deficiency 24
disease 25
Streptozotocin 123
Stroke 41, 90, 101, 120, 140, 143
complete 91
pathogenesis of 124
research 180
statistics 77
Stromal interaction molecule 1 56
Surface-connected canalicular system 18
Synthetic polyelectrolytes 194
Systemic disorders 22
Temporary vascular-assist devices 190f
Testing heart valves, customized chamber for 182f
Theophylline 184
Thorium dioxide 18
Thrombin 40, 79, 102
Thrombocythemia 22
Thrombocytopenia 22
heparin-induced 32, 83
Thrombocytopenic purpura 22
Thrombosis 101, 120
pathogenesis of 124
Thrombotic disease 1
Thrombotic status analyzer 124
Thromboxane 38, 40, 60, 62, 71, 102
A2 78
A2 receptor blocker 79
antagonists 91
dysfunction 30, 48
synthase and receptor 79
synthetase inhibitors 78, 79, 91
Thrombus formation 88
Ticlopidine 79
Tissue plasminogen activator 124
Trans-Golgi vesicles in mega-karyocytes 24
Transient ischemic attack 91, 143
Trifluoromethyl 114
Tumor necrosis factor 122
Turkey platelets 32
Typical integrin dimer 39f
Unstable coronary syndromes 139
Uremia 22
Vascular disease, peripheral 93
Vascular dysfunction 120, 126, 139, 168
Vascular ischemic events, acute 88
Vascular tissues 104
Vasculopathy 129
Verapamil 67
Vessel wall
shear stress 167
thickness 167
Visceral adiposity 88
B12 88, 138
D 88
E 91, 125
Vitronectin 4, 39, 46
von Willebrand disease 28
von Willebrand factor 4, 16, 28, 38, 39, 47, 79, 90, 102, 121, 127, 139, 168, 168f, 174f
Vulnerable atherosclerotic plaque, rupture of 137
Watson-Marlow-Bredel pumps 187
Western blot 41
Wiskott-Aldrich syndrome 2426, 27f
Zn-pyrophosphate 197
Chapter Notes

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Platelet Ultrastructure MorphologyCHAPTER 1

Abstract that Professor James G White wrote for his NIH Grant several decades ago best summarizes the type of work that we did at the Platelet Research Laboratory at the University of Minnesota, Medical School, Minneapolis, Minnesota.
“Investigations in this laboratory will continue to be directed toward development of knowledge on blood platelet function in normal hemostasis, its role in the pathogenesis of inherited and acquired bleeding disorders, and its contribution to vascular injury, thrombosis, and atherosclerosis. Analytical, scanning, and transmission electron microscopy, freeze-fracture, cytochemistry, and immunocytochemistry combined with cyclic nucleotide, adenine nucleotide, and prostaglandin biochemistry and advanced physiological techniques, including micropipette elastometry and lumi-aggregometry, will be used to develop new information on these problems and related areas. Particular emphasis has been placed on achievement of six specific aims. New approaches to the study of membrane ultrastructure will be used to identify physical alterations in platelet membranes and membrane systems not evident previously. Giant platelets with normal function from patients with the May-Hegglin anomaly will permit study of platelet membrane deformability before and after activation and surface receptor mobility (capping and patching) for the first time. Freeze-fracture and other sophisticated technology will be used to solve basic problems presented by inherited disorders of platelet function. A new mechanism of membrane modulation regulating platelet activation and the phenomenon of disaggregation and reaggregation of irreversibly aggregated platelets was recently discovered in this laboratory. It offers excellent opportunities to gain new knowledge of platelet biochemistry and physiology. Megakaryocytes can be concentrated and purified. We will recover them from a dog model permitting in-depth study of each stage of maturation and use of the techniques of structural physiology. Accomplishment of these aims will allow us to gain the knowledge required to control or prevent hemorrhagic and thrombotic disease.”
In the early days of thrombosis research, there was strong emphasis placed on the coagulation mechanisms in hemostatic reactions. In addition, preparation of platelets for studies posed a problem, as they were considered very fragile and very reactive. It was the appreciation that platelets were as important as coagulant proteins in the hemostasis and thrombosis processes that demanded the knowledge of their physiology, pathology, and function.1 A new era of ultrastructural investigation began in the early 1960s. Rapid developments in biochemistry and physiology had created the need for a more critical analysis of platelet fine structure and function. Cytochemical, immunochemical, and 2autoradiographic techniques capable of demonstrating specific chemical constituents in thin section of fixed platelets expanded the scope of ultrastructural investigations. A new concept of platelet anatomy, structural physiology and function was developed from electron microscopic investigations. By that time, I joined Dr White, he had already studied platelet ultrastructure for over a decade and published more than 200 articles on this topic.
Dr White in his “concept paper” on platelet structure, which was his HP Smith award lecture in 1978, emphasized the need to develop knowledge of basic relationships between platelet structure, biochemistry, and function in order to define the mechanisms involved in normal hemostatic activity and pathologic behavior (Figs. 1.1 to 1.5).
The specialized approach to identify these associations has been termed platelet structural physiology and pathology.1 Platelet in circulating blood has a “disk” or plate-like shape, with smooth convex contours (Fig. 1.5). Figure 1.2A represents a schematic diagram of a cross-section of a platelet showing internal structure and contents essential for executing physiological responses. Figure 1.2B shows cross-section of a platelet as seen in the electron microscope.
Primary purpose for the existence of circulating platelets is to keep a watch on the vessel wall, identify any injury or damage to the blood vessel, interact with the cell matrix of the injured wall, adhere, spread, cover the damaged site, and form an effective hemostatic plug. In order to emphasize this role, Professor White used to use a photograph of a “one in a million” shot of a platelet, which he used to refer as “cross-eyed platelet” (Fig. 1.4). Indeed, this photo of platelet became so famous that several commercial companies wanted to use it for promotional purposes.
I remember one company distributing small replica of “cross-eyed” sticky platelets made of some colored fabric to the participants at the International Society of Thrombosis and Hemostasis (ISTH) meetings.
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Fig. 1.1: Schematic representation of platelet ultrastructure shows platelet membrane-associated integrin (GpIIb/IIIa, GpIc/IIa), nonintegrin (GPV, vWF) glycoprotein domains, dense tubular system (DTS), open canalicular system, mitochondria, ACTIN, actin-binding protein, and microtubules. (GPV: Glycoprotein V; vWF: von Willebrand factor).
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Figs. 1.2A and B: (A) Schematic representation of a platelet. (B) Cross-section of a platelet as visualized by electron microscopy. (CM: Cell membranes; DB: Dense body; DTS: Dense tubular system; EC: Exterior coat; G: Alpha granules; Gly: Glycogen; MT: Microtubules; OCS: Open canalicular system; SMF: Submembrane filaments; Mi: Mitochondria; Gr: Granules; MC: Membrane channels).
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Fig. 1.3: Platelet from giant microbes.
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Fig. 1.4: Cross-eyed platelet.
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Fig. 1.5: Discoid platelets as seen by scanning electron microscopy.
Of course, Dr White did not like the idea and requested them to stop that practice. However, the very thought of a platelet with two eyes must have encouraged or inspired Giantmicrobes, Inc. of Wilmington DE ( to produce an attractive soft platelet look-alike with two eyes (Fig. 1.3).
In order to simplify the complicated structural features, internal contents, and relate them to activation mechanism, such as agonist receptor interactions, signal transduction events, biochemical and functional activities, Prof White divided the anatomy of a platelet into four major regions: the peripheral zone, the sol-gel zone, the organelle zone, and the platelet membrane system. Three basic mechanisms govern the activity of platelets in hemostasis: adhesion (aggregation), contraction, and secretion. The peripheral zone mediates all stimuli triggering the platelet response, and conversion from the nonsticky to sticky state takes place in this region.
The peripheral zone comprises the phospholipid membranes and the receptors and glycoprotein-rich domains, which play a major role in cell activation and signal transduction mechanisms. It consists of an exterior coat, or glycocalyx, rich in glycoproteins. Specific agonist receptors as well as integrin and nonintegrin domains, which are important for external stimulus coupling for platelet activation, are located at this zone. This zone is also rich in phospholipids. More than 15% of the dry weight of platelets is lipid of which 80% is phospholipid.2,3 Major lipids include cholesterol (30.8%), phosphatidylcholine (26.3%), phosphatidylethanolamine (8.6%), phosphatidylserine (6.6%), and phosphatidylinositol (2.7%). Recent research in lipidomics revealed the existence of over 8,000 species of lipids in platelets.4 At the time of this writing, the most prominent lipid substrates that played a major role in modulation of platelet and vessel wall functions were arachidonic acid, substrate for cyclooxygenase, thromboxane synthetase, and prostacyclin synthetase enzymes. In addition, a family of cell–cell and cell–surface receptors have been identified on platelet surface membranes.5 The first glycoprotein receptor to be identified was the 11b-111a complex, which when activated can bind four different adhesive proteins: fibrinogen, fibronectin, von Willebrand factor (vWF), and vitronectin. All of these adhesion receptors consist of two noncovalently associated alpha subunit (GPIIb) and beta subunit (GPIIIa). This complex is one of the most abundant receptor proteins present on the platelet surface membranes (> 50,000 copies). Integrin receptors are transmembrane glycoproteins with alpha and beta subunits (GPIIb-IIIa, GPIa-IIa, GPIc-IIa). In addition, there are nonintegrin (GPVI) glycoprotein domains on platelet surface membrane, capable of binding other cell matrix components such as collagen and vWF. In the activation mediated by collagen, integrin alpha-2, beta-1 (GPIIa-Ib), and nonintegrin GPVI are involved.
The sol-gel zone is the matrix of the cytoplasm. It contains fibers and filaments in various states of polymerization. This system of filamentous proteins, capable of polymerization and depolymerization supports the discoid shape in circulating platelets, and provides a contractile system for accomplishing shape change, pseudopod formation, spreading, contraction, and retraction. The contractile system constitutes 30% of the total platelet protein. Significant portion of this system is actin. Other proteins of this system 5include myosin, tropomyosin, actin-binding protein, alpha actinin, gelsolin, profilin, vinculin, and spectrin. In platelets, shape change, pseudopod formation, retraction, and spreading involve dissociation of existing actin structure and reformation of new ones. Thus, it is evident that these structural alterations are dynamic processes and are regulated by a large number of actin-binding proteins. In platelets, some of the proteins identified to play a role in such dynamic process are Arp2/3, cofilin, and capping protein, as well as 2E4/kaptin, gelsolin, VASP, and profilin.612 Actin is a globular monomer known to assemble reversibly to form long fibers. Actin fibers, if sufficiently stiff and organized into bundles, could maintain the cell and parts of the cell in particular configurations, for instance, pseudopods of platelets. Working with myosin could generate the contractility needed for spreading, release of granule contents, and clot retraction. Actin filaments could also act as ties for parts of the cell, including its membrane. It has become increasingly clear that action of actin is influenced by enormous number of actin-binding proteins.1218
The organelle zone consists of dense bodies, which are the storage sites for releasable components, such as ADP, ATP, calcium, and serotonin. Other components of this system include peroxisomes, lysosomes, mitochondria, and glycogen. This zone serves as the storage site for various enzymes, nonmetabolic adenine nucleotides, serotonin, and antioxidants such as taurine, ascorbic acid, and glutathione. On activation, platelets seem to secrete more than 300 active substances from their intracellular granules.13 Proteomic studies have demonstrated that hundreds of bioactive proteins are released from alpha granules.14 Though the role of these granule components was considered to play a role in thrombosis and hemostasis, recent studies have demonstrated their participation in inflammation, atherosclerosis, antimicrobial host defense, wound healing, angiogenesis, and malignancy.14
The membrane system plays a major role in platelet physiology, pathology, and function. The dense tubular system (DTS) has been shown to be the site where calcium, an important bioregulator, is sequestered. The DTS is also the site where enzymes involved in fatty acid metabolism and prostaglandin synthesis are localized.15 Platelet membrane system includes not only structures similar to endoplasmic reticulum (ER), which have been described by White as dense tubular system, but also the boundary or demarcation membranes of a variety of granular organelles within the cytoplasmic matrix: mitochondria, lysosomes, alpha-granules, and dense granules.16 Professor White has described two distinct channel systems in blood platelets.17 The open canalicular system, with its canaliculi, which are continuous with surrounding plasma, serves as a conduit for uptake of plasma-borne substances and as a path for extrusion of endogenous chemicals secreted during the platelet-release reaction.
A series of studies by White and associates have demonstrated that canaliculi of the open canalicular system (OCS) are continuous with the surrounding plasma, particles taken up by the system can be transferred to apparently intact granules, and channels remain open before, and after physical alterations during aggregation and release of secretory products. Existence of the two distinctly different membrane systems in platelets was described first by Behnke.19 White extended these studies to demonstrate a functional role for these membrane systems. On the basis of his extensive studies and that of other researchers working 6in this area, he concluded that platelets were not merely similar to muscle cells, but are muscle cells of the blood, and that contractile physiology dominated the functional activity of platelets in hemostasis.1618
  1. White JG. Current concepts of platelet structure. Am J Clin Pathol. 1979;71:363–78.
  1. Purdon D. Phospholipid metabolism in platelets. Mod Meth Pharmacol. 1987;4:229–42.
  1. Marcus AJ. The role of lipids in platelet function: with particular reference to arachidonic acid pathway. J Lipid Res. 1978;19:793–826.
  1. O'Donnell VB, Murphy RC, Watson SP. Platelet lipidomics: modern day perspectives on lipid discovery and characterization in platelets. Circ Res. 2014;114:1185–203.
  1. Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The Platelet membrane glycoprotein 11b-111a complex. Blood. 1988;71(4):831–43.
  1. White JG. The submembrane filaments of blood platelets. Am J Pathol. 1969;56:267–77.
  1. White JG. Arrangement of actin filaments in the cytoskeleton of human platelets. Am J Pathol. 1984;117:207–17.
  1. White JG, Rao GHR. Microtubule coil versus surface membrane cytoskeleton in maintenance of platelet discoid shape. Am J Pathol. 1998;152:597–609.
  1. Schollmeyer JV, Rao GHR, White JG. An actin-binding protein in human platelets. Interactions with alpha-actinin on gelation of actin and the influence of cytochalasin B. Am J Pathol. 1978;93(2):433–46.
  1. Bearer EL, Prakash JM, Li Z. Actin dynamics in platelets. Int Rev Cytol. 2002;217:137–82.
  1. Pollard TD, Cooper JA. Actin and actin-binding proteins: a critical evaluation of mechanisms and functions. Annu Rev Biochem. 1986;55:987–1035.
  1. Stossel TP. Contribution of actin to the structure of the cytoplasmic matrix. J Cell Biol. 1984;99(1):S15–S21.
  1. Golebiewska EM, Poole AW. Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 2015;29(3):153–62.
  1. Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev. 2009;23(4):177–89.
  1. Gerrard JM, White JG, Rao GH, Townsend D. Localization of platelet prostaglandin production in the platelet dense tubular system. Am J Pathol. 1976;83:283–98.
  1. Crawford N. Structural and molecular properties of platelet membrane. In: George JN (Ed). Platelet Membrane Glycoproteins. Plenum Press: New York;  1985.
  1. Cove DH, Crawford. Platelet contractile proteins: separation and characterization of the actin and myosin like components. J Mechanochem Cell Motil. 1975;3(2):123–33.
  1. White JG. Interaction of membrane systems in blood platelets. Am J Pathol. 1972;66(2): 295–312.
  1. Behnke O. Electron microscope observations on the membrane systems of the rat blood platelet. Anat Rec. 1967;158:121–37.