Platelet Function Inhibitors

Packham, Marian A.

doi:10.1055/s-0038-1665267

Cited by 52 publications

(12 citation statements)

References 69 publications

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“…3). Increased platelet aggregability is one of the aetiologic factors in thromboembolism (64). The increased platelet activation in ischaemic disorders is associated with an increased peripheral destruction of platelets and, consequently, also with a shortened megakaryocyte-platelet regeneration time (MPT) (65).…”

Section: Migraine and Thrombosismentioning

confidence: 99%

The Platelet and The Neuron: Two Cells in Focus in Migraine

Malmgren

Hasselmark

1988

Cephalalgia

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Reports of platelet abnormalities in migraine are abundant, and the present paper discusses the role of platelets in the migraine aetiology. Platelets are considered good models for pre- and post-synaptic functions in serotonergic neurons. We propose that migraine is associated with a lowered threshold for stimulus response in both platelets and serotonergic neurons and that the alterations in platelet function reflect central serotonergic disturbances. The platelet abnormalities in migraine approach those found in depression, and there are several links between the two disorders. The clinical significance of platelet hyperactivity in migraineurs for the occurrence of thrombotic disorders is also discussed. Studies of platelet functions in migraine, using platelets as models for serotonergic neurons, may broaden our understanding of the neuronal processes that take place during a migraine attack. The platelet can also be an investigative tool for better understanding of the modes of action of anti-migraine drugs.

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Section: Migraine and Thrombosismentioning

confidence: 99%

The Platelet and The Neuron: Two Cells in Focus in Migraine

Malmgren

Hasselmark

1988

Cephalalgia

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“…The responses to arachidonate, ADP, and epinephrine can be blocked by use of NSAI agents that inhibit cyclooxygenase ( Figure 1); aspirin inhibits this enzyme irreversibly. 86 Dazoxiben, an imidazole derivative that inhibits thromboxane synthetase but not the synthesis of endoperoxides, has a complex effect on arachidonate-induced platelet aggregation, because PGE 2 , a potentiator, and PGD 2 , an inhibitor, are formed. 92 Compounds of this type may prove more useful than NSAI in pre- venting thrombosis since they do not prevent the blood vessel wall from forming the platelet inhibitor prostaglandin l 2 (PGI 2 ) from endoperoxides.…”

Section: Secretionmentioning

confidence: 99%

Platelet activation.

Zucker¹,

Nachmias²

1985

Arteriosclerosis

204

101

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Platelets are discoidal cytoplasmic particles that respond to a variety of stimuli by developing filopodia and rounding up (shape change), developing the ability to bind fibrinogen from the medium, and, with strong stimuli such as thrombin and PAF-acether, secreting the contents of several types of granules. Arachidonic acid is cleaved from phospholipids by phospholipase A2 and converted by the platelets to endoperoxides, and then to thromboxane A2. The bound dimeric fibrinogen molecules probably cause aggregation by forming bridges between platelets. Aggregation is reinforced by secreted fibrinogen and thrombospondin, which binds the platelets, and by thromboxane A2 and endoperoxides, as well as secreted ADP, which cause additional receptor-mediated activation. The responses to these stimuli are initiated when the agonists bind to specific receptors on the plasma membrane. Subsequent steps resemble those in other types of responsive cells: breakdown of phosphatidylinositol bisphosphate into diacylglycerol, a stimulator of protein kinase C, and inositol-1,4,5-trisphosphate, recently shown to be a potent calcium ionophore. The response of shape change results from increased cytoplasmic Ca2+ which permits phosphorylation of one of the light chains of myosin by a calcium-calmodulin-dependent kinase, with resulting enhanced actin-myosin interaction. Secretion is associated with phosphorylation of a 40,000 to 47,000 dalton protein by the diacylglycerol-activated protein kinase C. These recent findings have increased our understanding of the mechanisms of platelet activation, but much remains to be learned. How do agonist-receptor complexes influence PIP2 breakdown? Is this indeed the first step in activation? What mediates adhesion of platelets to the injured blood vessel wall? Does transduction of this stimulus occur by the same mechanism as transduction of commonly used soluble stimuli? What is the role of the phosphorylated 40-47 K protein in secretion? What change in GP IIb-IIIa promotes their ability to bind fibrinogen? What is the role of calcium-activated protease? Of the phosphorylation of actin-binding protein? Progress is being made rapidly, and these questions may be answered within a few years.

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“…Antiplatelet drugs can inhibit platelet activation and adhesion to biomaterials and reduce calcium deposition while maintaining biostability ( 15, 16, 18, 19). It seems that human platelets possess membrane receptors for a wide variety of materials including fibrinogen and collagen ( 24). Thus, it is conceivable that antiplatelet drugs modify, mask, or prevent the expression of binding sites for adhesive proteins and cause a reduction of platelet densities on the surface.…”

Section: Discussionmentioning

confidence: 99%

Changes in Pericardial Calcification Due to Antiplatelet Agents: In Vitro Studies

1998

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To develop tissue valves for prolonged use in the cardiovascular system, the complicated process of surface induced calcification must be better understood. Calcification was examined for 60 days on glutaraldehyde treated bovine pericardium (GABP) and enzyme extracted tissues fixed in glutaraldehyde (GATBP) incubated in metastable solutions of calcium phosphate, and the roles of aspirin and persantine in conjunction with vitamins C, B, or E, gentamycin (antibiotic), or pentothal sodium (anesthetic) in the medium were examined. Further, the diffusion of calcium across the GATBP was evaluated using a diffusion cell with 2 compartments. Pericardial calcification was also observed using scanning electron microscopy (SEM) techniques. It seems that the examined antiplatelet agents can modify the pericardial surfaces and subsequently their mineralization processes (GATBP, 31.7 micrograms/mg tissue; in the presence of 5 mg% vitamin C, 13.1 micrograms/mg tissue; in 1.5 mg% aspirin, 17.2 micrograms/mg tissue; and 1 mg% gentamycin, 14.8 micrograms/mg tissue) on exposure with the metastable calcium phosphate solution for 60 days. In addition, these agents may modify calcium transport and interfere with the adsorption at the surface, hence reducing calcium nodulation on GATBP. Scanning electron micrographs also revealed a reduction in calcium deposition on the pericardium due to these antiplatelet agents. It may be hypothesized that the influx of calcium on GATBP may be due to the cellular components or the involvement of plasma proteins like the fibrinogen molecule. The exact mechanism of these changes in the calcification of the pericardium are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby for prevention of thrombosis and calcification. However, more in vivo studies are needed to develop applications.

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Platelet Function Inhibitors

Cited by 52 publications

References 69 publications

The Platelet and The Neuron: Two Cells in Focus in Migraine

The Platelet and The Neuron: Two Cells in Focus in Migraine

Platelet activation.

Changes in Pericardial Calcification Due to Antiplatelet Agents: In Vitro Studies

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