Platelet Electrophoresis: The Present Position^[*]

Summary

Measurements of platelet aggregation and adhesion have proved disappointing in the study of individual subjects with, or at risk from, arterial disease. In this paper the technique of platelet electrophoresis is described, and it is shown that with this technique individual patients with coronary artery disease can be identified with a high degree of accuracy. Abnormal platelet electrophoretic behaviour is also described in the relatives of subjects who have had a myocardial infarction at an early age, and it is suggested that the platelet abnormality precedes clinically-detectable disease.

The platelet abnormality is shown to be secondary to changes in the plasma, and experiments are described in which a start has been made in elucidating the nature of the plasma abnormality. Two plasma components are involved: one is probably adenosine diphosphate (ADP), and it is shown that ADP has two distinct effects on platelets; the other component is associated with the plasma low-density lipoproteins.

The nature of the low-density lipoprotein abnormality that induces platelet changes that can be detected by this electrophoretic technique appear of extreme importance in the understanding of thrombosis. No specific chemical abnormality has been identified in these lipoproteins, but certain detergents are shown to have a similar effect on platelet electrophoretic behaviour. It is therefore suggested that there are changes in the surface-active, or detergent, properties of the lipoproteins in subjects with, or at risk from, arterial disease.

^* Presented at the International Conference on “Platelets in Thrombosis : Their Clinical Significance and the Evaluation of Potential Drugs” in Titisee, Germany, October 1973.

• References

• 1 Abramson H. A. The electrophoresis of the blood platelets of the horse with reference to their origin and to thrombus formation. Journal of Experimental Medicine 1928; 47: 677
• 2 Bangham A. D, Flemans R, Heard D. R, Seaman G. V. F. An apparatus for micro-electrophoresis of small particles. Nature (Lond.) 1958; 182: 642
• 3 Bolton C. J, Hampton J. R, Mitchell J. R. A. Effect of oral contraceptive agents on platelets and plasma phospholipids. Lancet 1968; i: 1336
• 4 Brinkhous K. M. The problem in Perspective. In: Sherry S, Brinkhous K. M, Genton E, Stengle J. M. (eds.) Thrombosis National Academy of Sciences; Washington D. C.: 1969: 335
• 5 Cunningham C. C, Hager L. P. Crystalline pyruvic oxidase from Escherichia coli: activation by phospholipids. Journal of Biological Chemistry 1971; 246: 1575
• 6 Davison A. N, Graham-Wolfaard E. Quantitative analysis by thin-layer chromatography of cerebral lipids. Journal of Neuro chemistry II 1964; 147
• 7 Deutscher S, Ostrander L. D, Epstein F. H. Familial factors in premature coronary heart disease - a preliminary report from the Tecumsch Community Health Study. American Journal of Epidemiology 1970; 91: 233
• 8 Fiske C. H, SubbaRow Y. The colorimetric determination of phosphorus. Journal of Biological Chemistry 1923; 66: 375
• 9 Fredrickson D. S, Levy R. I, Lees R. S. Fat transport in lipoproteins - an integrated approach to mechanisms and disorders. New England Journal of Medicine 1967; 276: 34
• 10 Hampton J. R, Bolton C. H. Effects of phospholipids on platelet electro-phoretic mobility. Journal of Atherosclerosis Research 1969; 9: 131
• 11 Hampton J. R, Mitchell J. R. A. Effect of glass contact on the electro-phoretic mobility of human blood platelets. Nature (Lond.) 1966; a 209: 470
• 12 Hampton J. R, Mitchell J. R. A. Effect of aggregating agents on platelet electrophoretic behavior. British Medical Journal 1966; b i: 1074
• 13 Hampton J. R, Mitchell J. R. A. 1966; c Modification of the platelet-electro-kinetic response to aggregating agents. Nature (Lond.) 210: 1000
• 14 Hampton J. R, Mitchell J. R. A. Abnormalities in platelet behaviour in acute illnesses. British Medical Journal 1966; d i: 1078
• 15 Kagan A, Dawber T. R, Kannel W. B, Revotskie N. The Framingham Study: a prospective study of coronary heart disease. Federation Proceedings 1962; 21 (Suppl. 11) 52
• 16 Kemp H. G, Elliott W. C, Gorlin R. The anginal syndrome with normal coronary arteriography. Transactions of the Association of American Physicians 1967; 80: 59
• 17 Kerby G. P, Taylor S. M. Effect of palmitate on human platelet glycolysis and aggregation. Proceedings of the Society of Experimental Biology and Medicine 1970; 135: 355
• 18 De Lalla O. F, Gofman J. W. Methods of Biochemical Analysis. Glick D. (Ed.) Interscience; New York: 1954: 459
• 19 McDonald L, Edgill M. Coagulability of the blood in ischaemic heart disease. Lancet 1957; ii: 457
• 20 MacMillan D. C. Secondary clumping by adenosine diphosphate and adrenaline. Nature (Lond.) 1966; 211: 140
• 21 Nicholls D. G, Hampton J. R. Density gradient separation of human platelets from plasma, and the role of plasma in adenosine diphosphate-induced platelet electrophoretic mobility changes. Thrombosis et Diathesis Haemorrhagica 1972; 27: 425
• 22 O’Brien J. R, Heywood J. B, Heady J. A. The quantitation of platelet aggregation by four compounds : a study in relation to myocardial infarction. Thrombosis et Diathesis Haemorrhagica 1966; 16: 752
• 23 Poole J. C. F, French J. E. Thrombosis. Journal of Atherosclerosis Research 1 1961; 251
• 24 Seeman P. M. Membrane stabilisation by drugs, tranquilisers, steroids, and anaesthetics. International review of Neurobiology 1966; 9: 145
• 25 Sidd J. J, Kemp H. G, Gorlin R. Acute myocardial infarction in a nineteen-year-old student in the absence of coronary obstructive disease. New England Journal of Medicine 1970; 282: 1306