SummaryMembrane glycoprotein IIb/IIIa plays a major role in platelet function. The gene encoding the glycoprotein IIIa shows a common polymorphism PlA1/PlA2 that was variably associated with vascular disease. To clarify the role of PlA1/PlA2 polymorphism in coronary risk, a meta-analysis of published data was conducted. Studies were identified both by MEDLINE searches, and hand searching of journals and abstract books.A total of 34 studies for coronary artery disease (CAD), and 6 for restenosis after revascularization were identified, for a total of 9,095 cases and 12,508 controls. In CAD, the overall odds ratio for carriers of the PlA2 allele was 1.10 (95% CI: 1.03 to 1.18), and it was 1.21 (95% CI: 1.05 to 1.38) in subjects younger than 60. Overall odds ratio was 1.31 (95% CI: 1.10 to 1.56) after revascularization procedures.The association of PlA2 status with overall cardiovascular disease in the general population is significant but weak; higher risk has been identified in less heterogeneous subgroups as in the younger cohorts and in the restenosis subset with stents.

A B S T R A C T A qualitative platelet abnormality and a bleeding tendency are frequently associated with renal failure and uremia. We demonstrated previously that uremic patients display an abnormal platelet aggregation to arachidonic acid and reduced malondialdehyde production in response to thrombin and arachidonic acid. The objectives of this investigation were: (a) to compare platelet prostaglandin (PG) and thromboxane (TX) production in whole blood and in platelet-rich plasma (PRP) of 21 uremic patients and 22 healthy subjects; (b) to evaluate the concentration and activity of platelet PG-and TX-forming enzymes; (c) to assess the functional responsiveness of the platelet TXA2/PGH2 receptor; (d) to explore the hemostatic consequences of partially reduced TXA2 production.Platelet immunoreactive TXB2 production during whole blood clotting was significantly reduced, by "60%, in uremic patients as compared to age-and sex-matched controls. Exogenous thrombin (5-30 IU/ ml) failed to restore normal TXB2 production in uremic platelets. Uremic PRP produced comparable or slightly higher amounts of TXB2 than normal PRP at arachidonate concentrations 0.25-1 mM. However, when exposed to substrate concentrations >2 mM, uremic PRP produced significantly less TXB2 than normal PRP. To discriminate between reduced arachidonic acid oxygenation and altered endoperoxide Portions of this work were presented at the Eastern Section

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The potencies of prostaglandins (PG) I2, PGD2 and PGE1 as inhibitors of human platelet aggregation induced by threshold concentrations of four aggregating agents were determined in platelet-rich plasma from normal individuals who had not ingested aspirin. The order of activity against ADP, adrenaline and collagen was always PGI2 greater than PGD2 greater than PGE1. However, PGD2 and PGE1 were almost equipotent with PGI2 when tested against arachidonic acid (AA). The threshold inhibitory effects of PGD2, PGE1 and PGI2 could be over come by increasing the concentrations of the aggregating agents AA, collagen or ADP. Adrenaline was found to be different from the other aggregating agents. It could overcome inhibition of platelet aggregation by PGD2 but could not overcome inhibition by PGI2 or PGE1. These facts support the hypothesis that platelet receptors for PGI2 and PGE1 are similar to each other and different from the receptor(s) for PGD2. PRP obtained from normal subjects after the ingestion of aspirin exhibited only one wave of aggregation in response to ADP, adrenaline or collagen, PGI2, PGD2 and PGE1 were all powerful inhibitors of this single wave of aggregation. The inhibitory activity of all three prostaglandins at threshold concentrations was overcome by increasing the concentration of ADP or collagen but not by increasing the concentration of adrenaline.

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We studied platelet function and antithrombrin III levels in 30 insulin-dependent diabetic children with no clinically evident vascular complications. 9 were in-patients and 21 were out-patients. The disease had been discovered within the previous 10 years. 25 control subjects of comparable age and body weight were studied simultaneously. Template bleeding time, threshold concentrations of ADP or adrenaline required to induce irreversible platelet aggregation and plasma antiheparin activity (platelet factor 4) did not differ significantly in control and patient groups. In contrast, the immunological levels of plasma antithrombin III were significantly higher in the diabetic group. These results suggest that diabetic children, with no clinical signs of microangiopathy, show no laboratory changes suggesting increased platelet function. The unexpected increase in the antithrombin III level could reflect a very early defense mechanism against activation of the blood clotting system.