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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

Reinhard MischkeClinic for Small Animals, School of Veterinary Medicine of Hanover, Bischofsholer Damm 15, D-30173 Hannover, Germany.

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Susanne GrebeClinic for Small Animals, School of Veterinary Medicine of Hanover, Bischofsholer Damm 15, D-30173 Hannover, Germany.

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Christina JacobsClinic for Small Animals, School of Veterinary Medicine of Hanover, Bischofsholer Damm 15, D-30173 Hannover, Germany.

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Manfred KietzmannInstitute for Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bünteweg 17, D-330559 Hannover, Germany.

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Abstract

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 (each injection, 150 U of anti-factor-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 sixth 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 of 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 the sixth injection). Thrombin time and APTT were influenced only slightly. Platelet count, Hct, and antithrombin activity started to decrease significantly 2 hours after the second LMWH injection. Because of the increased consumption 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.

Conclusion and Clinical Relevance—Heparin plasma activity was only slightly higher than that recommended for LMWH treatment of humans, and none of the 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 monitoring LMWH treatment of dogs. Assays that use chromogenic substrates are necessary to reliably monitor LMWH plasma concentrations in dogs. (Am J Vet Res 2001;62:595–598)

Abstract

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 (each injection, 150 U of anti-factor-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 sixth 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 of 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 the sixth injection). Thrombin time and APTT were influenced only slightly. Platelet count, Hct, and antithrombin activity started to decrease significantly 2 hours after the second LMWH injection. Because of the increased consumption 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.

Conclusion and Clinical Relevance—Heparin plasma activity was only slightly higher than that recommended for LMWH treatment of humans, and none of the 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 monitoring LMWH treatment of dogs. Assays that use chromogenic substrates are necessary to reliably monitor LMWH plasma concentrations in dogs. (Am J Vet Res 2001;62:595–598)