Thrombin‐, Epinephrine‐ and Collagen‐Induced Platelet Aggregation Inhibited by α₁‐Acid Glycoprotein

Abstract

α1‐acid glycoprotein (α1‐acid GP) isolated from human plasma was found to inhibit thrombin‐induced aggregation of washed human platelets (final thrombin concentration 0.05 NIH U/ml), and inhibition was complete with physiological concentrations of the glycoprotein (1.0–1.5 g/l final conc.). The inhibitory effect seemed to occur immediately on thrombin addition, thus being similar to the effect of heparin previously observed. As opposed to heparin, however, α1‐acid GP did not affect spontaneous platelet aggregation. Furthermore, α1‐acid GP (in optimal concentrations) reduced the combined inhibitory effect of heparin and antithrombin III on thrombin‐induced platelet aggregation, thus being consistent with the previous findings using heparin thrombin clotting time. Snyder & Coodley (1976) found α1‐acid GP to inhibit platelet aggregation induced by epinephrine and adenosine diphosphate in platelet‐rich plasma. As we also found α1‐acid GP to inhibit collagen‐induced platelet aggregation, this acid glycoprotein may possibly act as an inhibitor of the release reaction although fairly high concentrations (10 mg/ml final conc.) were needed for complete inhibition.

Inhibition of Thrombin‐Induced Platelet Aggregation by Crude and Highly Purified α1‐Acid Glycoprotein

“…Highly purified al-acid GP prepared from crude glycoprotein was found to possess an inhibitory effect on thrombin-induced platelet aggregation identical to the effect of the crude preparation (Figure 1). Earlier investigations have shown that albumin had no such inhibitory effect on thrombin-induced (Eika & Abildgaard 1970, Andersen & Eika 1980a. Moreover, transferrin possessed no inhibitory effect on platelet aggregation induced by ADP or epinephrine in platelet-rich plasma (Snyder & Coodley 1976).…”

“…The inhibitory effect of al-acid glycoprotein (a,-acid GP) on thrombin-, epinephrineand collagen-induced platelet aggregation has recently been reported (Andersen & Eika 1980a). Further investigations revealed that the acid glycoprotein used in these earlier experiments was grossly contaminated with albumin and transferrin, and trace impurities of al-antithrombin I11 (AT-111) were regiilarly present.…”