DIFFERENTIAL ACTIVITIES OF HEPARINS IN HUMAN-PLASMA AND IN SHEEP PLASMA - EFFECTS OF HEPARIN MOLECULAR SIZES AND SOURCES

We analyzed the anticoagulant activity of heparins in human plasma and in sheep plasma upon recalcification using the technique of clot elasticity measurement. Heparins with different molecular weight (M.W.) distributions, fractionated by Ultrogel AcA 44 gel chromatography, and heparins from different sources were analyzed in these two coagulation systems. In both systems, heparin with M.W. approximating 20,000 showed the highest specific activity; activities dropped with either increasing or decreasing M.W. Activities of each heparin fraction in these two clotting systems were not parallel. The differences were strongly dependent on the M.W. and sources. The activity-M.W. curves determined in these two clotting systems crossed at a position with M.W. 17,000, a value in the middle of the M.W. range of most commercial heparins (approximately 12,000 to 20,000). This indicates that the United States Pharmacopoeia (USP) method, which uses sheep plasma, underestimates the anticoagulant activity of heparins in human plasma with M.W. between 17,000 and 25,000 and overestimates that with M.W. lower than 17,000. The greatest discrepancy was found with the smallest M.W. fraction (6,200); an 800% difference was observed. Discrepancies were also observed with heparins from different sources. The USP method using porcine mucosal standard underestimates the potency of a gut heparin in human plasma by a factor of 1.5, and overestimates potencies of heparins from beef origin, either mucosal or lung material, by approximately 20%. A heparin preparation isolated from whale showed no discrepancy. © 1978.