Amidolytic heparin activity and values for several hemostatic variables after repeated subcutaneous administration of high doses of a low molecular weight heparin in healthy dogs

Objective-To determine effects of SC administration of repeated doses of a low molecular weight heparin (LMWH) in dogs. Animals-5 healthy dogs, Procedure-Each dog received 6 injections teach injection, 150 U of anti-fac tor-Xa [anti-FXa]/kg of body weight, SC) at 8-hour intervals. Blood samples were collected before and 2 hours after the first, second, third, and sixt h injections to measure heparin activity, thrombin time, activated partial thromboplastin time (APTT), antithrombin activity, Hct, and platelet count. Results-Heparin activity varied between 0.36 =/- 0.10 and 0.77 +/- 0.08 U o f anti-FXa/ml (before and 2 hours after the third injection) and between 0. 46 +/- 0.11 and 0.82 +/- 0.15 U of anti-FXa/ml (before and 2 hours after th e sixth injection). Thrombin time and APTT were influenced only slightly. P latelet count, Hct, and antithrombin activity started to decrease significa ntly 2 hours after the second LMWH injection. Because of the increased cons umption of antithrombin, antithrombin activity continuously decreased from 102.1 +/- 6.3% before the study to 91.0 +/- 3.0% at the end of the study. Conclusions and Clinical Relevance-Heparin plasma activity was only slightl y higher than that recommended for LMWH treatment of humans, and none of th e dogs had signs of increased bleeding. Thus, administration of heparin in accordance with this dosing regimen can be recommended for use in clinical studies. The screening tests investigated were not suitable for use in moni toring LMWH treatment of dogs. Assays that use chromogenic substrates are n ecessary to reliably monitor LMWH plasma concentrations in dogs.