The effects of mezlocillin, ticarcillin and placebo on blood coagulation and bleeding time in normal volunteers.

Bleeding time, coagulation tests and platelet aggregation response to adenosine diphosphate (ADP), epinephrine, arachidonic acid, ristocetin and collagen were determined in 18 normal male volunteers in a randomized, double-blind, placebo-controlled parallel study. Six subjects each received either placebo or 4.0 g of either mezlocillin or ticarcillin every 6 h for 7 days. In the placebo-treated or mezlocillin-treated groups no changes in plasma coagulation tests or bleeding time were observed. Randomly scattered decreases in platelet aggregation responses to ADP, epinephrine or arachidonic acid were noted in some subjects in both the placebo and mezlocillin groups. In contrast to these observations, in the ticarcillin treated group the bleeding time was abnormally prolonged to more than 18 min in three of six volunteers. In two of these subjects, bleeding time was prolonged after only seven ticarcillin doses (28.0 g) and in the third subject after a total of 21 doses (84.0 g). A significant decrease in platelet aggregation (P less than 0.005) induced by ADP was found in these volunteers. Although platelet aggregation response to arachidonic acid and epinephrine also appeared to be reduced in this group, correlation between increased bleeding time and abnormal platelet function was not possible because of the small number of subjects. No changes in other coagulation function were observed. The results suggest that the risk of bleeding disorder is very high with therapeutic doses of ticarcillin but not with comparable doses of mezlocillin.