Activity of Synthetic Phospholipids in Blood Coagulation

Abstract

Summary1. An investigation was made into the activity of synthetic phospholipids on blood coagulation in vitro, utilizing synthetic substances including phosphatidyl ethanolamine and phosphatidyl serine containing a poly-unsaturated fatty acid constituent.2. Applying a one-stage recalcification test, phosphatidyl serine was found to act at high concentrations as anticoagulant. No clot-promoting activity was observed after addition of individual phospholipids. However, several combinations of phospholipids, e.g. phosphatidyl ethanolamine with phosphatidyl serine or certain mixtures of lecithin with phosphatidylserine, shortened the clotting time.3. In the thromboplastin generation test phosphatidyl ethanolamine exhibited some acceleratory activity without being able, however, to replace crude brain cephalin completely. However, optimal coagulant activity was produced by mixtures of synthetic phospholipids viz, phosphatidyl ethanolamine with phosphatidyl serine, phosphatidic acid or (isolated) cardiolipin and by certain combinations of lecithin and phosphatidyl serine.4. In both assay systems the maximum activity of each phospholipid combination was found to be related within certain limits to the ratio of both compounds. It is concluded that the coagulant activity of phospholipids in vitro is not to be attributed to a certain type of phospholipid or a defined mixture. The results obtained with the synthetic compounds appear to support the view that a particular negative surface charge of the phospholipid micelles is a prerequisite for maximal clot-promoting activity of phospholipids.

Comparison of Phospholipid and Fatty Acid Composition of Human Erythrocytes and Platelets

“…This activity can be 'unmasked' in the erythrocyte by disrupting the cell (Georgatsos, Hussey and Quick, 1955) or even by exposing the intact cell to subhaemolytic concentrations of glycerol (Cohen, 1967) or other straight-chain dihydroxyl or polyhydroxyl compounds (Cohen, 1968). It has also been shown by Rouser and Schloredt (1958) and Daeman and van Deenen (1963) that di-unsaturated, as opposed to monoor di-saturated synthetic ethanolamine phosphoglyceridcs, are more active in certain iiz vitro clotting tests. 6.…”

Platelet Phospholipids and Stypven Clotting Time

“…Most phospholipids, especially phosphatidylserine, exhibit some clotting activity whether isolated from platelets, erythrocytes, other tissues or synthesized (2,7,8,21). Several experiments appear to indicate that the clotting activity of phospholipids rather depends on the surface charge of the phosphatide micelles (14,20).…”

Effects on blood coagulation, fibrinolysis, and platelet aggregation of normal and atheromatous aortic tissue

“…The responsible factor within the vessel has not been identified, but as the active platelet component in the thromboplastin generation test is probably a phospholipid (Troup, Reed, Marinetti, and Swisher, 1960;Alkjaersig, Abe, and Seegers, 1955) it is possible that the atheromatous lesion acts by virtue of its increased phospholipid content. It appears that a combination of phospholipids may be necessary for maximal generation of intrinsic thromboplastin (Daemen, van Arkel, Hart, van der Drift, and van Deenen, 1965), and it is probable that the clot-promoting activity of phospholipids is related to the surface charge of the lipid micelles. FIBRINOLYSIS No significant difference was noted when the antifibrinolytic activity of normal and atheromatous aorta was compared in the urokinase sensitivity test, suggesting that atheromatous aorta does not potentiate intravascular thrombosis by local reduction of thrombolysis.…”