Effect of Certain Sulfur Compounds on Coagulation of Blood

The initial observation of Mueller and Sturgis 1 that cysteine inhibits the coagulation of whole blood in vitro has since been confirmed and elaborated by Carr and Foote, 2 who suggested that the delay in coagulation might be due to certain changes which they observed in the physical state of the fibrinogen. Kühnau and Morgenstern, 3 working with glutathione, also described inhibition of coagulation within a certain range of pH. Since the mechanism of the reaction has not been explained, the experiments reported here have been undertaken. Three lines of investigation have been carried out:

1. In vivo experiments in human subjects. Cysteine and methionine, ingested and injected intravenously in amounts varying from 1 to 3.5 gm., prolonged the bleeding time as indicated by the Ivy method from a 4 minute upper limit of normal to 15 minutes (methionine, 1.31 gm. intravenously) and delayed the coagulation time as shown by the 8 mm. tube method, from an 8 minute upper normal to 16 minutes (cysteine, 1 gm. intravenously and methionine, 1.31 gm. intravenously).

2. In vitro experiments with whole blood. Cysteine hydrochloride, taurocholic acid, taurine, methionine, glycine, alanine and cysteic acid, neutralized to pH 7, were added in graded amounts giving final concentration of from 4.4 × 10^-5 M to 0.18 M, and the coagulation time was determined by the 8 mm. tube method. Glycine, alanine and cysteic acid did not retard coagulation. Methionine, in contrast to its behavior in vivo, also had no effect in delaying coagulation. Cysteine produced a significant effect at a 0.046 M concentration, with a coagulation time of 18 minutes. At 0.18 M concentration, the coagulation time was 53 minutes. Taurine showed a definite effect at 0.023 M concentration (16 minutes), with a 90 minute coagulation time at 0.18 M concentration. Taurocholic acid produced a significant effect at 0.011 M concentration (34 minutes), with no coagulation during 24 hours in concentrations of 0.023 to 0.18 M.