Effect of polyribonucleotides on in vitro platelet aggregation induced by acid-soluble collagen and other aggregating agents.

This investigation was conducted in an attempt to determine if a reported case of disseminated intravascular coagulation (DIC) in a patient receiving polyriboinosinic-polyribocytidylic acid [poly (I). poly(C)] could be related to an effect of poly (I) . poly (C) on platelet aggregation. It was determined that poly (I) poly (C), while not inducing platelet aggregation by itself, produced a decrease in latency and an increase in the rate of platelet aggregation induced at 37#{176}and 24#{176}C by acid-soluble collagen (ASC). All activity resided in the poly (I) strand, which produced a significant effect in a concentration as low as 0.1 zg/ml of plasma (0.22 lLmole phosphorus/liter). At concentrations up to 0.25 mg/mI no activity was observed with polyriboadenylic acid-polyribouridylic acid, while polyriboguanylic acid had an inhibitory effect in concentrations down to 2.5 g/ml (0.54 Mmole P/ liter). Similarly, moieties of poly (I), inosine, and inosine 3’and 5’-monophosphoric acid lacked activity. Inhibition of ASC polymerization by ascorbic acid diminished the effect of poly (I) on platelet aggregation, while poly (I) alone enhanced ASC polymerization. Since poly (I) was found not to affect platelet aggregation induced by particulate collagen, it was concluded that it enhanced ASCinduced platelet aggregation by promoting collagen polymerization. Poly (I) in high concentrations (about 0.05 mg/mI) was found to inhibit platelet aggregation induced by adenosine diphosphate, epinephrine, and ristocetin. The inhibitory effect, however, did not appear incompatible with the appearance of a thrombotic disorder since plasma concentrations in vivo probably fall rapidly below the effective inhibitory concentration. The reported presence of a soluble form of collagen (procollagen) in human serum and the identification in arterial thrombi of collagen that may be derived from this source provide a possible link between poly(l) and DIC.