Four Heparin Preparations: Anti-Xa Potentiating Effect of Heparin after Subcutaneous Injection

Summary

Four different heparin preparations - sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m. w. 9,000) and high molecular weight sodium heparin (mean m. w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i. u./ml) at 3-4 hours after the injection. With sodium heparin (m. w. 15,000) the highest values (0.135 i. u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0. 072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 1. u./ml at 3-4 hours after injection).

These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

^* Coagulation Laboratory, Northwick Park Hospital

^** St. Thomas’ Hospital and Medical School, London, S. E. 1., England

• 1 An International Multicentre Trial. 1975; Prevention of fatal post-operative pulmonary embolism by low doses of heparin. Lancet II: 45.
• 2 Braswell E. 1968; Heparin: molecular weight and degradation studies. Biochemica et Biophysica Acta 158: 103.
• 3 British Pharmocopoeia. 1973 p.A 112
• 4 Brozović M, and Bangham D. R. 1974; Standards for heparin. Advances in Experimental Medicine and Biology 52: 163.
• 5 Brozović M, Stirling Y, Klenerman L, and Lowe L. 1974; Subcutaneous heparin and post-operative thrombosis. Lancet II: 99.
• 6 Brozović M, Stirling Y, and Abbosh J. 1975; Plasma heparin levels after low dose subcutaneous heparin in patients undergoing hip replacement. British Journal of Haematology 31: 131.
• 7 Denson K. W. E, and Bonnar J. 1973; The measurement of heparin. Thrombosis et Diathesis Haemorrhagica 30: 471.
• 8 Estes J. W. 1971; The kinetics of heparin. Annals of the New York Academy of Sciences 179: 187.
• 9 Gallus A. S, Hirsh J, Tuttle R. J, Trebillock R, O’Brien S. E, Carroll J. J, Minden J. H, and Hedecki S. M. 1973; Small subcutaneous doses of heparin in prevention of venous thrombosis. New England Journal of Medicine 288: 545.
• 10 Johnson E. A. Metachromatic assay methods for heparin and protamine. To be published.
• 11 Kakkar V. V, Corrigan T, Spinaler J, Fossard D. P, Flute P. T, Crellin R. Q, Wessler S, and Yin E. T. 1972; Efficacy of low doses of heparin in prevention of deep vein thrombosis after major surgery. Lancet II: 101.
• 12 Lasker S. E, and Stivala S. S. 1966; Physicochemical studies of fractionated bovine heparin. Archives of Biochemistry and Biophysics 115: 360.
• 13 Machovich R, Blasko G, Himer A, and Szikla K. 1975; Effect of sodium and potassium on the activity of human antithrombin-heparin cofactor. Thrombosis Research 7: 305.
• 14 Thomas D. P, Sagar S, and Kakkar V. V. 1975 Heparin and Factor Xa I levels in patients undergoing hip surgery. Abstract of Vth Congress of the International Society of Thrombosis and Haemostasis Paris p. 438