Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

In a study comparing the in vitro effects of heparin and a low molecular weight heparinoid (Organon 10172) on aggregation of platelets from normal subjects, we have demonstrated that whereas heparin markedly enhances platelet aggregation induced by other aggregators and inhibits the anti-aggregatory effect of epoprostenol (prostacyclin, PGI2), heparinoid does not produce such effects. The use of heparinoid may thus have a significant advantage over that of heparin in situations where enhanced platelet aggregation is the main factor leading to thrombosis or where heparin treatment is followed by thrombocytopaenia.

Effect of nonesterified fatty acids on the stability of prostacyclin activity.

The half-life of the platelet antiaggregatory activity of prostacyclin (PGI2) is prolonged when PGI2 is incubated in human plasma or in fatty-acid-free human albumin solutions. This "PGI2-protective" effect is diminished when fatty acids are added to the incubate, and the diminution is proportional to the concentration of the nonesterified fatty acids added. Unsaturated fatty acids were more potent in causing this reduction than saturated acids. It is possible that nonesterified fatty acids displace PGI2 from binding sites on the albumin molecule and that they may thus alter the biologic half-life of any circulating PGI2. This observation may partly account for the well-documented association between raised serum nonesterified fatty acid levels and thrombosis/platelet activation.

Effect of human plasma proteins on stabilisation of platelet anti-aggregatory activity of prostacyclin.

Following the demonstration that biological activity of prostacyclin is more stable in plasma than in buffer solutions at physiological pH, we investigated the possibility that a plasma protein may be responsible for this effect. The duration of platelet anti-aggregatory activity of prostacyclin in fatty acid-free human albumin solution was significantly longer than in buffer solutions. The duration of this 'protection' was proportional to the concentration of albumin; alpha, beta, and gamma-globulin preparations had no 'protective' effect. The degree of 'protection' by albumin solutions was lower than that by plasma despite identical albumin concentrations. This discrepancy may in part be explained by the tendency of plasma to become alkaline on standing, a change that would tend to stabilise prostacyclin. The clinical relevance of our findings is discussed.

Protection of prostacyclin-like activity in human plasma-a non-enzymatic mechanism?

1. The rate of decay of the platelet antiaggregatory activity of prostacyclin in plasma and buffer solutions was investigated. 2. Platelet anti-aggregatory activity of prostacyclin was more stable in plasma than in buffer solutions at physiological pH. 3. The rate of decay of this activity increased with an increase in incubation temperature. 4. Preheating of plasma at 65 degrees C led to a marked but not total loss of its ability to "protect" prostacyclin. 5. Incubation of 6-keto prostaglandin F 1 alpha in plasma did not result in the appearance of platelet anti-aggregatory activity; nor did the decay curves of prostacyclin activity indicate the emergence of any new platelet anti-aggregatory activity. 6. Incubation of 6-keto-prostaglandin E1 in plasma did not lead to any loss of its platelet anti-aggregatory activity for prolonged periods. 7. We conclude that the marked prolongation of platelet anti-aggregatory activity of prostacyclin in plasma is not due to its enzymatic conversion into 6-keto-prostaglandin E1 but due to 'protection' of prostacyclin itself. This 'protection' is probably due to an interaction with a plasma protein.