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

Mischke, R.; Grebe, S; Jacobs, C.; Kietzmann, Manfred

doi:10.2460/ajvr.2001.62.595

Cited by 32 publications

(33 citation statements)

References 20 publications

(27 reference statements)

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“…In a study by Mischke et al, 19 peak anti‐FXa activity 2 hours after a single injection of 100 U/kg to dogs in vivo was 0.43 U/mL of plasma. With repeated SC injections of 150 U/kg dalteparin every 8 hours, plasma anti‐FXa activity was 0.77 U/mL of plasma and 0.82 U/mL at 2 hours after the third and sixth injections 20 . The supratherapeutical concentrations pose a limitation in the present study with regard to the direct clinical applicability of the results, and further evaluations of the heparinase‐modified, TF‐activated TEG assay with doses in the recommended clinical range, followed by prospective clinical studies, are required to assess the performance and usefulness of heparinase‐modified, TF‐activated TEG in a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose‐dependently prolongs heparinase‐modified tissue factor‐activated thromboelastography parameters and prothrombinase‐induced clotting time

Jessen

Wiinberg

Jensen

et al. 2008

Veterinary Clinical Pathol

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Background: Low-molecular-weight heparin (LMWH) is being used increasingly in veterinary medicine for both treatment and prophylaxis of thromboembolic disease, but no predictable patient-side method exists to monitor its effect. Objectives: The aim of this study was to evaluate thromboelastography (TEG) and prothombinase-induced clotting time (PiCT) assays for detecting hemostatic alterations following in vitro heparinization of canine whole blood with dalteparin (Fragmin). Methods: Citrated whole-blood samples were collected from 7 clinically healthy dogs. Dalteparin was added at concentrations of 0, 0.156, 0.625, 1.25, and 2.5 U/mL of whole blood. TEG was performed using heparinase cups with tissue factor (TF, 1:50,000) and kaolin as activators. Reaction time (R), clotting time (K), angle (a), and maximum amplitude (MA) were recorded. PiCT and anti-FXa activity were measured in plasma. Results: With TF, increasing concentrations of dalteparin significantly prolonged R and K and significantly decreased a and MA. K, a, and MA ratios were significantly different from baseline at all dalteparin concentrations and R was significantly different from baseline at concentrations of 0.625, 1.25, and 2.5 U/mL. With kaolin, only R was significantly different from baseline at dalteparin concentrations of 0.625 and 2.5 U/mL. PiCT detected dalteparin concentrations 0.625 U/mL, with a good linear correlation (r 2 = .96, P o.0001). Conclusion: These results suggest that TF-activated TEG and PiCT assays should be further evaluated as promising new methods for evaluating the effect of LMWH, using doses in the recommended clinical range and prospective clinical studies.

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Section: Discussionmentioning

confidence: 99%

In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose‐dependently prolongs heparinase‐modified tissue factor‐activated thromboelastography parameters and prothrombinase‐induced clotting time

Jessen

Wiinberg

Jensen

et al. 2008

Veterinary Clinical Pathol

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“…The human therapeutic target for AXa was not met for any dog in the LDH or DP groups. Because of these disparities, future studies with LMWH should be designed to evaluate the heparin activity produced by higher doses than the dose of DP that was used here, as originally suggested by Mischke 33 based on work in healthy dogs. If UFH is used in clinical studies, the HDH protocol is indicated but requires close therapeutic monitoring.…”

Section: Discussionmentioning

confidence: 99%

“…Therapy with LMWH is associated with fewer complications such as heparin‐induced thrombocytopenia and requires less monitoring due to the standardized dose and predictable response in humans. Success with this product in human medicine has prompted interest in studying the use of LMWH in dogs for the prevention of venous thrombosis 33 …”

Section: Introductionmentioning

confidence: 99%

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis

Scott

Hansen

DeFrancesco

2009

J Vet Emergen Crit Care

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“…LMWH may also lower the risk of bleeding side‐effects because it shows more specific activity against coagulation factor Xa 33 . Several dosing regimes for LMWH administration in dogs have been suggested, from 100 IU/kg once a day to 150 IU/kg 2 or 3 times a day, depending on the LMWH used, the therapeutic goal, and the patient's clinical status 10,34–36 . Reduced LMWH doses and routine monitoring are advised in human renal failure patients, because the anti‐factor Xa activity of LMWH is strongly correlated with creatinine clearance 33 .…”

Section: Discussionmentioning

confidence: 99%

Canine leishmaniasis with nephrotic syndrome and aortic and caudal vena cava thromboembolism

Félix¹,

Mouro²,

Vilela³

et al. 2008

J Vet Emergen Crit Care

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Objective – To describe a case of leishmaniasis associated with nephrotic syndrome and aortic and caudal vena cava thrombosis in a dog. Case Summary – A 3‐year‐old male Boxer was referred to the Faculty of Veterinary Medicine, Lisbon, with vomiting, polyuria, polydipsia, lethargy, anorexia, and weight loss. On admission, the dog was thin, quiet, and dehydrated. Initial laboratory abnormalities were compatible with a diagnosis of leishmaniasis (confirmed by serology and bone marrow aspirate), and nephrotic syndrome. Three days later, the animal developed lumbar pain, paraparesis, and absent femoral pulses. Coagulation tests showed a marked reduction in antithrombin (AT) and a mild increase in serum fibrinogen concentration. A diagnosis of thromboembolism was made. In spite of treatment aimed at controlling the primary condition and decreasing further thrombus formation, necrosis developed in the distal right pelvic limb and the nail beds of the left pelvic limb. Against medical advice, medication was stopped and, 15 days later, the dog returned to the hospital, showing extensive necrosis of both pelvic limb extremities. Euthanasia was performed at the owner's request. Necropsy showed a thrombus localized at the distal aorta and extending into the right iliac artery, and an additional thrombus extending from both femoral veins onto the caudal vena cava. New or Unique Information Provided – Thromboembolic disease is rare in dogs with leishmaniasis with nephrotic syndrome. This case suggests that a marked decrease in AT and a mild increase in serum fibrinogen may elicit a hypercoagulable state in these patients.

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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

Cited by 32 publications

References 20 publications

In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose‐dependently prolongs heparinase‐modified tissue factor‐activated thromboelastography parameters and prothrombinase‐induced clotting time

In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose‐dependently prolongs heparinase‐modified tissue factor‐activated thromboelastography parameters and prothrombinase‐induced clotting time

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis

Canine leishmaniasis with nephrotic syndrome and aortic and caudal vena cava thromboembolism

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