Anti-Heparin and Platelet Aggregation Activities of Polyamino Acids

An earlier report from this laboratory has described the antagonism of the anticoagulant effect of heparin by certain basic polyamino acids. Of the numerous polyamino acids tested, only basic polyarnino acids such as poly-L-lysine (MW 85,000) and poly-L-omithine (MW 120,000) effectively neutralized heparinized plasma (1 u/ml) in concentrations less than 10 μg/ml. Addition of these two polyamino acids in quantities up to 50 μg/ml citrated plasma, significantly shortened the thrombin time. Poly-L-proline (MW 19,000), poly-L-histidine (MW 16,000) and poly-L-lysine (MW 85,000) possessed weak anti-heparin action. These polyamino acids also neutralized the anticoagulant activity of hirudin and polyanetholsulfonic acid in varying degrees. The effects of polyamino acids on platelet aggregation was also tested. Of the 15 basic polyamino acids tested, only poly-L-α-omithine was found to induce aggregation of platelets. Polyornithine in the amounts of 50.0, 25.0 and 12.5 μg/ml to platelet rich plasma caused a 65, 45 and 30% change in transmittance, respectively. The polyornithine induced aggregation (PIA) of platelets was only partially blocked by acetylsalicylic acid. Contrast media (6.0 mg/ml) used in diagnostic radiology and meglumine (5 mg/ml) totally blocked the PIA. The PIA of platelets was found to be a biphasic process, an initial lag time of 30 seconds, after which irreversible aggregation was observed. These studies suggest that basic polyamino acids may be used clinically to antagonize overheparinization; in addition, polyornithine may prove useful in the diagnosis of platelet function defects.