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Journal ArticleDOI

The effect of prostaglandin E1 on platelet function in vitro and in vivo.

01 Nov 1970-British Journal of Haematology (Blackwell Publishing Ltd)-Vol. 19, Iss: 5, pp 559-571
TL;DR: It is concluded that the effect of PGE1 on haemostasis involves inhibition of the release of ADP from platelets exposed to collagen and thrombin, and inhibition ofADP‐induced aggregation.
Abstract: Summary Low concentrations of prostaglandin E1 (PGE1) inhibit ADP-induced aggregation in pig and rabbit citrated platelet-rich plasma and in suspensions of washed platelets. Higher concentrations also inhibit the initial change in shape induced by ADP and the release of platelet ATP, ADP and serotonin caused by stimuli such as collagen, thrombin, antigen-antibody complexes and gamma-globulin-coated polystyrene particles. PGE1 is not taken up by platelets and its effects can be removed by resuspending platelets in fresh medium. Immediately following an intra-arterial injection, ADP-induced platelet aggregation is suppressed, but after 5 min the response returns to normal. PGE1 inhibits haemostasis in rabbits when given as a continuous infusion. It is concluded that the effect of PGE1 on haemostasis involves inhibition of the release of ADP from platelets exposed to collagen and thrombin, and inhibition of ADP-induced aggregation.
Citations
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Journal ArticleDOI
TL;DR: It is worthwhile to review the complex interrelations between platelets and fibrinolysis, with emphasis on the therapeutic potential (and risks) of combining thrombolytic therapy.
Abstract: FIBRINOLYTIC therapy is a major advance in the treatment of occlusive vascular disease. Problems remain, however, including resistance to fibrinolytic therapy, delays in reperfusion, reocclusion after successful thrombolysis, and serious hemorrhage.1 2 3 Increasing evidence indicates that platelets have an important role in both delaying reperfusion and mediating reocclusion. In addition, preliminary data suggest that some thrombi resist lysis because they are rich in platelets and that platelet dysfunction contributes to the hemorrhagic diathesis associated with thrombolytic therapy. It is worthwhile, therefore, to review the complex interrelations between platelets and fibrinolysis, with emphasis on the therapeutic potential (and risks) of combining thrombolytic . . .

480 citations

Journal ArticleDOI
TL;DR: Prostaglandin D2, heretofore considered to be biologically inactive, was found to be more than twice as potent as prostaglandsin E1 as an inhibitor of aggregation in human citrated platelet-rich plasma.

213 citations

Book ChapterDOI
TL;DR: This chapter focuses on demonstrating the overall resemblance of the release of mediators by immunologically induced noncytotoxic reactions to secretory processes, in general.
Abstract: Publisher Summary This chapter describes the noncytotoxic release of mediators from cells induced in vitro by immunological stimuli. It discusses the release of mediators from these same cells by nonimmunological means. It focuses on demonstrating the overall resemblance of the release of mediators by immunologically induced noncytotoxic reactions to secretory processes, in general. The chapter describes the chemotaxis and phagocytosis by polymorphonuclear leukocytes; release of lysosomal enzymes from the latter cells by staphylococcal toxin; leukocidin; aggregation of platelets; and the specifically and nonspecifically induced transformation of lymphocytes. In the context of this chapter, the term “mediators” is restricted to substances whose release is directly or indirectly initiated by an immunological reaction and are responsible for one or more of the manifestations of the subsequent allergic response.

174 citations

Journal ArticleDOI
04 Jun 1976-Science
TL;DR: Sodium archidonate-induced shape change and aggregation of platelets may be caused by the release of ADP by products of sodium arachidonate metabolism and (ii) directly by the products of Sodium arachidenate metabolism, independently of released ADP.
Abstract: Sodium arachidonate causes shape change and aggregation of rabbit or human platelets that have been washed and then degranulated by treatment with thrombin. Since these platelets do not contain releasable adenosine diphosphate (ADP) and the aggregation is not inhibited by the creatine phosphate-creatine phosphokinase system, sodium arachidonate must be able to cause aggregation that is independent of the release of ADP. Since aggregation of these platelets induced by sodium arachidonate is inhibited by acetylsalicylic acid or indomethacin, it seems likely that products (such as prostaglandin G2) formed from sodium arachidonate are responsible for aggregation. Thus, sodium arachidonate-induced shape change and aggregation of platelets may be caused (i) by the release of ADP by products of sodium arachidonate metabolism and (ii) directly by the products of sodium arachidonate metabolism, independently of released ADP.

118 citations

Journal ArticleDOI
01 Jan 1975-Drugs
TL;DR: The effects of drugs which inhibit platelet function are outlined and the extent to which they can be used to influence the course of thromboembolic disease in man is discussed.
Abstract: The development of thrombosis involves 4 main factors: the vessel wall, the formed elements of the blood, blood coagulation, and blood flow. In venous thrombosis, however, the major part in both the initiation and growth of thrombi is played by the platelets. In selecting drugs which inhibit platelet function it is helful to know which of the platelet reactions that contribute to thrombus formation can be inhibited by various agents. Platelets adhere to the damaged vessel wall, collagen being probably the most important constituent involved. They are then stimulated to release the contents of their storage granules. Release-inducing agents promote the discharge of adenosine diphosphate (ADP) which causes platelets in the vicinity to swell to a more spherical shape, extend pseudopods and adhere to each other. Platelet aggregation is reversible, and a number of drugs have been shown to be capable of inhibiting platelet function at various stages, both in vitro and in vivo. Adrenaline, noradrenaline, oestrogens and nicotine enhance aggregation. Drugs which inhibit platelet function include the non-steroidal anti-inflammatory drugs, the pyrimido-pyrimidines (e.g. dipyridamole), hydroxychloroquine, clofibrate, and dextran. In this review the effects of drugs which inhibit platelet function are outlined and the extent to which they can be used to influence the course of thromboembolic disease in man is discussed. It is suggested that combination of anti-platelet drugs with anticoagulants could prove clinically useful.

107 citations

References
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Journal ArticleDOI
02 Dec 1967-Nature
TL;DR: The liver and lungs provide an efficient protective mechanism to remove almost all the prostaglandin before it reaches the arterial circulation.
Abstract: Prostaglandins are released into the splenic venous blood when the spleen contracts Whatever the significance of this release, the liver and lungs provide an efficient protective mechanism to remove almost all the prostaglandin before it reaches the arterial circulation

842 citations

Journal ArticleDOI
TL;DR: On comparison with rabbit platelets prepared from blood taken into EDTA, the only differences observed were the much greater sensitivity to ADP and a higher calcium content; platelet morphology, nucleotide levels, and conversions of 14C‐ATP and 14C-ADP at the platelet membrane were similar.
Abstract: Summary A method is described for the preparation of suspensions of washed rabbit platelets which will aggregate upon the addition of low concentrations of ADP that are effective in citrated plasma. This method involves collecting blood into ACD, low pH, removal of calcium, and maintenance of magnesium during the isolation procedure. A protein (albumin) and glucose are included in the washing and suspending solutions. Rabbit platelets prepared in this way retained fibrinogen on their surface. On comparison with rabbit platelets prepared from blood taken into EDTA, the only differences observed were the much greater sensitivity to ADP and a higher calcium content; platelet morphology, nucleotide levels, and conversions of 14C-ATP and 14C-ADP at the platelet membrane were similar.

394 citations