Effects of Unfractionated Heparin, Low-Molecular-Weight Heparin, and Heparinoid on Thromboelastographic Assay of Blood Coagulation

Zmuda, K.; Neofotistos, Demetra; Ts’ao, Chung-hsin

doi:10.1309/q4ae-bmcw-cq7j-nuvt

Cited by 77 publications

(75 citation statements)

References 21 publications

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“…[7][8][9][10][11] In addition, several studies have specifically evaluated the utility of TEG as a surrogate monitor of LMWH therapy in humans, albeit with contrasting results. [7][8][9] This study established a reference range for TEG parameters for healthy cats and demonstrated an effect of heparin therapy on TEG. However, in the current study, only UFH had a significant effect on TEG when R values were evaluated.…”

Section: Discussionmentioning

confidence: 99%

Anticoagulant Effects of Low‐Molecular‐Weight Heparins in Healthy Cats

Alwood

Downend

Brooks

et al. 2007

Veterinary Internal Medicne

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Background: Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG).Hypothesis: Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG.Animals: In vivo research with heparin was performed in 5 purpose-bred cats.Methods: In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time.Results: Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/ mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours.Conclusions: Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic antifactor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.

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Section: Discussionmentioning

confidence: 99%

Anticoagulant Effects of Low‐Molecular‐Weight Heparins in Healthy Cats

Alwood

Downend

Brooks

et al. 2007

Veterinary Internal Medicne

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“…Klein et al [9] analyzed the relationship of thromboelastography and serum anti-Xa levels in postoperative patients treated with the LMWH and enoxaparin and found that the value of thromboelastography significantly correlates with the levels of anti-Xa activity and the degree of anticoagulation produced by low molecular weight heparin. Zmuda et al [10] studied the effect of unfractionated heparin, and a heparinoid on blood clotting assayed with TEG in vitro and the efficacy of protamine sulfate and heparinase for reversing the effect.…”

Section: Introductionmentioning

confidence: 99%

Heparin-induced effects of prothrombin complex concentrates in thromboelastometry

Scharbert

Thaler

Weilnböck

et al. 2012

Wien Klin Wochenschr

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“…Using thromboelastography (TEG), reversal of enoxaparininduced prolongation of clotting by heparinase was used to detect enoxaparin concentrations of 0.2 anti-Xa IU/ml or greater; however, there were inconsistencies among the different assay parameters (R, k and a) [13]. In a more recent study with TEG, there was a marked loss in linearity between LMWH concentration and reaction time (time to beginning of clot formation, R) at concentrations of LMWH above 0.5 IU/ml.…”

Section: Discussionmentioning

confidence: 99%

Toward development of a point-of-care assay of enoxaparin anticoagulant activity in whole blood

Inchiosa

Pothula

Kubal

et al. 2011

J Thromb Thrombolysis

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There is need for a rapid assay to determine the efficacy of low-molecular-weight-heparin (LMWH) in whole blood. Heparinase was used to eliminate, and thereby quantify, the anticoagulant activity of the low-molecular-weight-heparin, enoxaparin. The percent change in the clotting time of whole blood in the presence of heparinase yielded the anticoagulant contribution of enoxaparin. A minimally activated assay (MAA) of whole blood clotting time was evaluated for the detection and relative quantification of enoxaparin. The assay cartridge consisted of a plain glass tube and detection magnet, with no additional sources of activation. Comparisons were also made with a point-of-care, activated partial thromboplastin time (aPTT) assay. Plasma or whole blood was spiked with enoxaparin at concentrations ranging from 0.1 to 1.0 anti-factor Xa IU/ml. A commercial preparation of heparinase I was used to digest enoxaparin, and clotting times were determined with and without heparinase incubation. Heparinase digestion caused an average shortening of clotting time of 21.1% (47.3 s) in blood spiked with 0.4 anti-Xa IU/ml enoxaparin, an amount expected in the therapeutic range; also, 0.1 anti-Xa IU/ml of enoxaparin could be reliably detected. The assay performed comparably when transferred to a point-of-care setting with heparinase being added directly to citrated blood collection tubes, followed by either MAA or aPTT assay. Strong correlations were obtained with both assays between the percent change in clotting time (after heparinase) and the added concentration of enoxaparin, or in comparison with the chromogenically measured concentration of enoxaparin. The assays for an individual blood sample can be completed within 10 min.

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Effects of Unfractionated Heparin, Low-Molecular-Weight Heparin, and Heparinoid on Thromboelastographic Assay of Blood Coagulation

Cited by 77 publications

References 21 publications

Anticoagulant Effects of Low‐Molecular‐Weight Heparins in Healthy Cats

Anticoagulant Effects of Low‐Molecular‐Weight Heparins in Healthy Cats

Heparin-induced effects of prothrombin complex concentrates in thromboelastometry

Toward development of a point-of-care assay of enoxaparin anticoagulant activity in whole blood

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