Subscribe to RSS
DOI: 10.1055/s-0038-1656225
Activity of Synthetic Phospholipids in Blood Coagulation
Publication History
Publication Date:
24 July 2018 (online)
Summary
1. 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.
-
References
- 1 Bangham A. D. A correlation between surface charge and coagulant action of phospholipids. Nature 4: 1197 1961
- 2 Barkham P, Schier M. J, da Costa P. B, Tocantins L. M. Phosphatidyl serine and blood coagulation. Nature 182: 1031 1958;
- 3 Bidwell E, Biggs R. Development of platelet like activity of crude egg phospholipid. J. Physiol. 138: 37-38 1957;
- 4 Biggs R, Bidwell F. An attempt to identify a single phospholipid active in blood coagulation. Brit. J. Haemat. 3: 387 1957;
- 5 Biggs R, Douglas A. S. The thromboplastin generation test. J. clin. Path. 6: 23 1953;
- 6 Daemen F. J. M. Syntheses of Phosphatidyl ethanolamines and application of synthetic phosphatides in studies on blood coagulation. Thesis (1963), Drukkerij Elinkwijk, Utrecht, the Netherlands
- 7 Daemen F. J. M, van Deenen L. L. M. Activity of synthetic phospholipids in blood clotting. Biochem. J. 88: 32 1963;
- 8 Daemen F. J. M, de Haas G. H, van Deenen L. L. M. On the synthesis of mixed-acid L-a-phosphatidyl ethanolamines. Ree. Trav. chim. Pays-Bas 81: 349 1962;
- 9 Daemen F. J. M, de Haas G. H, van Deenen L. L. M. An improved synthesis of a mixed-acid L-a-phosphatidyl ethanolamine containing a poly-unsaturated fatty acid. Ree. Trav. chim. Pays-Bas 82: 487 1963;
- 10 Folch J. Complete fractionation of brain cephalin. J. biol. Chem. 177: 497 1949;
- 11 de Haas G. H, Daemen F. J. M, van Deenen L. L. M. The site of action of phospholipase A on mixed acid phosphatides containing a poly-unsaturated fatty acid. Biochim. biophys. Acta 65: 260 1962;
- 12 de Haas G. H, van Deenen L. L. M. Synthesis of enantiomeric mixed-acid phosphatides. Ree. trav. chim. Pays-Bas 80: 951 1961;
- 13 de Haas G. H, van Deenen L. L. M. Some properties of a synthetic mixed acid phosphatidyl serine. Proc. kon. ned. Akad. C. 64: 592 1961;
- 14 de Haas G. H, van Deenen L. L. M. Cardiolipin and derivatives. Ree. trav. chim. 82: 1163 1963;
- 15 de Haas G. H, Heemskerk C. H. T, van Deenen L. L. M, Baker R. W. R, Gallai-Hatchard J, Magee W. L, Thompson R. H. S. The mode of action of human pancreatic phospholipase A. In: Frazer A. C. Biochemical problems of Lipids. 249 Elsevier; Amsterdam: 1963
- 16 de Haas G. H, van Zntphen H, Bonsen P. P. M, van Deenen L. L. M. Synthesis of mixed acid phosphatidyl serine containing unsaturated fatty acids. Ree. trav. chim. Pays-Bas 83: 99 1964;
- 17 Hecht E, Slotta K. H. The chemical nature of the Lipid Activator in Blood Coagulation. Amer. J. Clin. Path. 37: 126 1962;
- 18 Hjort P, Rapaport S. I, Owren P. A. A simple specific one-stage prothrombin assay using Russell’s viper venom in cephalin suspensions, J. Lab. clin. Med. 46: 89 1955;
- 19 Hoelzl-Wallach D. F, Maurice P. A, Steele B. B, Surgenor D. M. Studies on the Relationship between the Colloidal State and Clot-promoting Activity of pure Phosphatidyl ethanol-amines. J. biol. Chem. 234: 2829 1959;
- 20 Kögl F. G. H, de Haas L. L. M. van Deenen. The preparation of a series of L-a-lecithins. Ree. trav. chim. Pays-Bas 79: 661 1960;
- 21 Kuhn R, Klesse P. Zur chemischen Konstitution des Lipoids der Gewebe Thrombokinase. Z. Physiol. Chem. 312: 214 1958;
- 22 Marcus A. J, Spaet H. Platelet phosphatides, their separation, identification and clotting activity. J. clin. Invest. 37: 1836 1958;
- 23 Marcus A. J, Oilman H. L, Safier L. B, Ballard H. S. Platelet phosphatides. Their fatty acid and aldehyde composition and activity in different clotting systems. J. clin. Invest. 41: 2198 1962;
- 24 Mustard J. F, Medway W, Downie H. G, Rowsell H. G. Effects of intravenous phospholipid containing phosphatidyl serine on blood clotting with particular reference to the Russell’s Viper venom time. Nature 196: 1063 1962;
- 25 O’Brien J. R. The similarity of the action of phosphatidyl ethanolamine and platelets in blood coagulation. J. clin. Path. 9: 47 1956;
- 26 Papahadjopoulos D, Hougie G, Hanahan D. J. Influence of surface charge of Phospholipids on their Clot-Promoting activity. Proc. Soc. exp. Biol. med. Ill: 412 1962;
- 27 Poole J. C. F, Robinson D. S. Further observations on the Effects of Ethanolamine Phosphatide on Plasma Coagulation. Quart. J. Physiol. 41: 295 1956;
- 28 Rapport M. M. Activation of phospholipid thromboplastin by lecithin. Nature 178: 591 1956;
- 29 Robinson D. S, Poole J. G. F. The similar effect of chylomicra and ethanolamine phosphatide on the generation of thrombin during coagulation. Quart. J. exp. Physiol. 41: 36 1956;
- 30 Rouser G, Schloredt D. The fatty acid composition of the active phosphatidyl ethanolamines. Biochim. biophys. Acta 28: 81 1958;
- 31 Rouser G, White S. G, Schloredt D. Phospholipid structure and thromboplastic activity I. The phosphatide fraction active in recalcified normal human plasma. Biochim. biophys. Acta 28: 71 1958;
- 32 Silver M. J, Turner D. L, Rodalewiez J, Giordano N, Holburn R, Herb S. F, Buddy F. E. Evaluation of activity of Phospholipids in Blood Coagulation in Vitro. Thrombos. Diathes. haemorrh. (Stuttg.) 10: 164 1963;
- 33 Silver M. J, Turner D. L, Tocantins L. M. Phospholipid antithromboplastin: Assay in vitro and evaluation in vivo of purified Fractions. Amer. J. Physiol. 190: 8 1957; .
- 34 Slotta K. H. Thromboplastin I. Phospholipid moiety of thromboplastin. Proc. Soc. exp. Biol. 103: 53 1960;
- 35 Slotta K. H, Deutsch E. Thromboplastic activity of split products of phosphatidyl ethanolamine. Thrombos. Diathes. haemorrh. (Stuttg.) 4: 283 1960;
- 36 Therriault D, Nichols T, Jensen H. Purification and identification of brain phospholipids associated with thromboplastic activity: J. biol. Chem. 233: 1061 1958;
- 37 Troup S. B, Reed C. F. Platelet thromboplastic factor. Its chemical nature in vitro activity, and the identification of similar thromboplastic substances in red blood cells. J. clin. Invest. 37: 937 1958;
- 38 Troup S. B, Reed C. F, Marinetti G. V, Swisher S. N. Thromboplastic factors in platelets and red blood cells: observations on their chemical nature and function in in-vitro coagulation. J. clin. Invest. 39: 342 1960;
- 39 Turner D. L, Holburn R. R, DeSipin M, Silver M. J, Tocantins L. M. Thromboplastic activity of phosphatidyl ethanolamine from natural and synthetic sources. J. Lipid Res. a: 52 1963;
- 40 Turner D. L, Silver M. J. Total synthesis of unsaturated phosphatidyl serine and its activity in Clotting systems. Nature 200: 370 1963;