William R. Pritchard Veterinary Medical Teaching Hospital, University of California
Davis, CA, USA
Hydroxyethyl starch, with an average molecular weight 600kd and degree of substitution 0.7 (HES), is an artificial colloid solution commonly used in veterinary medicine. HES has been shown to decrease platelet function in humans in vivo, indicated by prolonged closure times (CT) as measured by the Platelet Function Analyzer-100® (PFA-100®). HES has also been shown to decrease canine platelet function in vitro by prolonging CT. Our hypothesis was that intravenous HES in vivo prolongs CT in dogs.
Eight healthy, employee-owned dogs were included in the treatment group. Four of these dogs also served as the control group. Washout period between experimental protocols for the control group was a minimum of 4 weeks. Baseline platelet count was greater than 100,000/μl in all dogs. CTs were measured using collagen and adenosine diphosphate platelet agonists. Dogs were given 20mL/kg of either NaCl 0.9% (control group, n=4) or HES (treatment group, n=8) IV over one hour. Blood was drawn for CT before the infusion, and at 1, 3, 5, and 24 hours after the start of the infusion. Two-way repeated measures analysis of variance was used to assess changes over time, and differences between control and treatment groups. Time-specific group differences were evaluated using Student's t-test with a sequentially rejective method of multiple comparison adjustment.
There was a significant change over time from 0 to 24 hours (p=0.0001), a significant difference between groups across time (p=0.0004), and evidence of a significant group-by-time interaction (p=0.0069). At 3 hours, mean CT for the treatment group was 122.3 ± 18.1 seconds, which was significantly different (p=0.0002) from the control group (71.0 ± 3.5 seconds). At 5 hours, mean CT for the treatment group was 142.7 ± 33.9 seconds, which was significantly different (p=0.0014) from the control group (75.0 ± 8.6 seconds). Mean CT at 24 hours was within the reference interval for both the control and treatment group (66.0 ± 2.9 seconds and 81.8 ± 11.9 seconds respectively), however CT in three individual dogs in the treatment group at this time point remained prolonged.
Given these results, a clinically relevant dose of HES adversely affects platelet function, as assessed by closure time. Individual dogs may still have decreased platelet function 24 hours after a single 20mL/kg dose of HES, and therefore, an increased risk of bleeding.