Neutralization of Heparin by Histone and Its Subfractions

The neutralization of heparin by histone and its subfractions has been systematically studied by measuring the effect of heparin on the esterolytic and proteolytic activity of thrombin. These results were compared with protamine sulfate, a most commonly used heparin-neutralizing agent. This study reveals that potencies of different fractions of histone are not similar. The antiheparin potency is in the order: lysine-rich histone greater than crude histone greater than arginine-rich histone. Histone binds strongly to heparin - Sepharose gel. The ability of histone to bind heparin can be utilized to fractionate heparin. By affinity chromatography on histone - Sepharose gel commercial heparin has been fractionated into components having a wide range of anticoagulant activities. The highest activity fraction, eluted around 1.0 NaCl, has 66% higher anticoagulant activity than the commercial heparin used.