Inhibition of platelet function in thrombosis.

Abstract:

:Accumulating experimental and clinical evidence indicates that a time for reappraisal of therapeutic modalities designed to inhibit the eicosanoid pathway as it may affect vascular disease may be approaching. Pharmacologic agents originally used were chosen because they were capable of suppressing platelet functions such as aggregation, release, and adhesion. The goals of clinical trials were to evaluate medications that would prevent or reduce platelet accumulation in critically located blood vessels of the heart, brain, and extremities and on vascular prostheses. Evaluation of results of therapeutic trials has been difficult and this is superimposed on less-than-complete knowledge of the basic pharmacology of the drugs that have been used. Participation of neutrophils and possibly macrophages in the thrombotic process is now well recognized on morphologic grounds. Because different cell types such as platelets, neutrophils, and endothelial cells have been shown to interact biochemically by sharing precursors and intermediates of the eicosanoid pathway, the pharmacologic approach to inhibition of vascular disease may require reevaluation. Neutrophils appear to lack a cyclooxygenase pathway but serve as a source of the lipoxygenase product leukotriene B4 (LTB4). Actions of LTB4 include neutrophil aggregation, adhesion of neutrophils to endothelial cells, chemotaxis, chemokinesis, and plasma exudation. We have demonstrated in vitro that released free arachidonic acid from aspirin-treated platelets can serve as a source of neutrophil LTB4. Leukotrienes C4, D4, and E4 are agonists for various functions of vascular endothelium and smooth muscle. Most pharmacologic agents used in the treatment of vascular diseases inhibit the cyclooxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Circulation

journal_title

Circulation

authors

Marcus AJ,Safier LB,Ullman HL,Broekman MJ,Islam N,Oglesby TD,Gorman RR,Ward JW

doi

10.1161/01.cir.72.4.698

subject

Has Abstract

pub_date

1985-10-01 00:00:00

pages

698-701

issue

4

eissn

0009-7322

issn

1524-4539

journal_volume

72

pub_type

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