Pharmacokinetics and pharmacodynamics of a therapeutic dose of unfractionated heparin (200 U/kg) administered subcutaneously or intravenously to healthy dogs

Abstract

Objectives:To evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after IV and SC administration and to compare these effects with plasma heparin concentrations assessed by its anti Xa activity.Methods: 200 U/kg of UFH were administered Intravenously (IV) and Subcutaneously (SC) to five healthy adult Beagle dogs with a wash out period of at least 3 days. Activated Partial Thromboplastin Time (APTT), Prothrombin Time (PT) and plasma anti-factor Xa (aXa) activity were determined in serial blood samples.Results: After IV injection, PT remained unchanged except for a slight increase in one dog;APTT was not measurable (> 60 s) for 45 to 90 min, then decreased regularly and returned to baseline values between 150 and 240 min. High plasma heparin concentrations were observed (C max = 4.64±1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semi-logarithmic curve but returned to baseline slightly more slowly (t240 to t300 min). Heparin concentrations were grossly correlated to APTT; prolongation of APTT of 120 to 160% corresponded to plasma heparin concentrations range of 0.3-0.7 aXa U/mL, considered as the therapeutic range in human medicine. Conclusions:As in human, pharmacokinetic of UFH in dogs is non linear. Administration of 200 U/kg of UFH SC in healthy dogs results in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. This has to be confirmed in diseased animals.

Viscoelastic pharmacodynamics after dalteparin administration to healthy dogs

“…5 There is also evidence that LMWHs are more effective at preventing postsurgical thrombotic complications in human patients. 7,8 Target prolongation of aPTT to 1.5 to 2.0 times the patient' s baseline values has been accepted in clinical practice for anticoagulation with UFH, but this remains controversial and is not useful for monitoring treatment with LMWH. 7,8 Target prolongation of aPTT to 1.5 to 2.0 times the patient' s baseline values has been accepted in clinical practice for anticoagulation with UFH, but this remains controversial and is not useful for monitoring treatment with LMWH.…”

Bovine and porcine heparins: different drugs with similar effects on human haemodialysis

“…The dilution of the patient plasma with normal human plasma was necessary in order to reduce the clotting time in the presence of the high concentration of heparin, administered during the dialysis session. Similar limitation for the use of undiluted plasma to monitor plasma concentration of heparin was previously reported [14]. After 2 min of incubation at 37°C, 100 μL of 25 mM CaCl2 was added to the mixtures, and the clotting time was recorded in a coagulometer (Amelung KC4A; Heinrich Amelung GmbH, Lemgo, Germany).…”

“…Based on this equation we can derive the amounts of anticoagulant activity in 30 μL of patient plasma and obtain the value as IU mL -1 . The plasma concentration of heparin assessed by aPTT assay strongly correlates with anti-Xa activity and other coagulation assays [14]. …”

Thromboembolic Conditions, Aetiology Diagnosis and Treatment in Dogs and Cats

“…It may be administered as an initial i.v. dose (100 to 200 IU/kg), then 50 to 100 IU/kg s.c.q6-8h then adjusted to prolong aPTT to about one and a half to two times of the pre-treatment values (Diquélou et al 2005). LMWH has potential benefit in cats at risk for ATE disease.…”