Anticoagulant effects of repeated subcutaneous injections of high doses of unfractionated heparin in healthy dogs

To evaluate s.c. administration of unfractionated heparin (UFH) in accordance with a dosing regimen for high-dose treatment in dogs. 10 healthy adult Beagles. Two groups of dogs (5 dogs/group) were given 6 injections of heparin (500 units of UFH/kg of body weight, s.c.) at intervals of 8 (experiment 1) and 12 (experiment 2) hours. Blood samples were collected before and 4 hours after heparin injections to determine amidolytic heparin activity, activated partial thromboplastin time (APTT), thrombin time, antithrombin activity, platelet count, and Hct. For experiments 1 and 2, mean +/- SD heparin activities before (experiment 1, 1.32 +/- 0.20 U/ml; experiment 2, 0.69 +/- 0.174 U/ml) and 4 hours after the last heparin injection (experiment 1, 1.71 +/- 0.30 U/ml; experiment 2, 1.10 +/- 0.30 U/ml) were higher than values calculated for the regimen used in experiment 1. Results of the investigated thrombin time test system with low thrombin activity were frequently beyond the measurement range, even with UFH activities > or = 0.6 U/ml. Moreover, a severe decrease of antithrombin activity became evident during both experiments (eg, in experiment 2 from 95.6 +/- 4.8 to 59.2 +/- 6.6%). In each treatment group, 2 dogs developed hematomas. Calculations of the course of heparin activity after a single injection do not result in a reliable dosing regimen for high-dose heparin treatment in dogs. High-dose treatment must be monitored for each dog. Thrombin time measured with low thrombin activity is unsuitable for this purpose.