The effect of Hetastarch (670/0.75) in vivo on platelet closure time in the dog

Objective To evaluate the effect of 6% hydroxyethyl starch (HES) solution in vivo, with an average molecular weight of 670 kDa and degree of substitution of 0.75, on canine platelet function. Design Prospective, controlled- experimental study. Setting University of California, Davis, Veterinary Medical Teaching Hospital. Animals Seven healthy employee-owned dogs. Interventions Seven dogs were included in the treatment group. Four of these dogs also served as the control group. Platelet closure time (CT) was measured using a platelet function analyzer and collagen/ADP cartridges. Dogs were given 20 mL/kg of either sodium chloride 0.9% (control group, n=4) or HES (treatment group, n=7) IV over 1 hour. CT was measured before the infusion, and at 1, 3, 5, and 24 hours after the start of the infusion. Measurements and Main Results There was a significant change over time from 0 to 24 hours (P<0.001), a significant difference between groups across time (P<0.001), and a significant group-by-time interaction (P=0.007). At 3 hours, mean CT for the treatment group was 122.3±18.1 seconds, which was significantly different (P<0.001) from the control group (71.0±3.5 s). At 5 hours, mean CT for the treatment group was 142.7±33.9 seconds, which was significantly different (P=0.001) from the control group (75.0±8.6 s). Mean CT at 24 hours was within the reference interval for both the control and treatment group (66.0±2.9 and 81.8±11.9 s, respectively); however, CT in 3 individual dogs in the treatment group at this time point remained prolonged. Conclusions A clinically relevant dose of HES 670/0.75 prolongs CT in dogs for up to 24 hours. This may be due to platelet dysfunction in addition to the effects of hemodilution, and therefore, may increase the risk of bleeding.