A comparison of the quantitative action of protamine and heparin on blood coagulation. Significance in clinical and laboratory usage.

Protamine is a considerably weaker anticoagulant than heparin. At a concentration in plasma of 0.05 mg (5 units/ml), heparin rendered the plasma incoagulable, while protamine produced only a mild-to-moderate lengthening of activated partial thromboplastin time (APTT) and prothrombin time (PT). Protamine concentrations between 0.3 and 1.0 mg/ml of plasma produced marked prolongation of APTT and PT, but the thrombin time (TT) was shortened. Between protamine concentrations of 1 and 2 mg/ml of plasma, the fibrinogen was precipitated to a variable degree, the APTT and PT were more than 200 sec, and the TT was moderately prolonged. High doses of protamine prolonged APTT, simulating heparin effect. Although APTT is prolonged both by heparin and protamine, TT is either normal or shortened in protamine excess and prolonged in heparin excess. To differentiate between the protamine and heparin excess, a combination of APTT and TT, supplemented by an estimation of fibrinogen and fibrin-fibrinogen split products, is recommended. The significance of these observations in the interpretation of the tests on blood coagulation is discussed.