Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor

Bara, L.; Bloch, Marie-Françoise; Zitoun, D.; Samama, M; Collignon, F.; Frydman, Armand; Uzan, A.; Bouthier, J.

doi:10.1016/0049-3848(93)90233-e

Cited by 62 publications

(50 citation statements)

References 20 publications

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“…20,21,27,28 On the other hand, supratherapeutic doses of heparin were unable to inhibit CFRs in this model. The antithrombotic efficacy of enoxaparin was demonstrated clinically in the recent ESSENCE trial, in which enoxaparin was shown to be superior to heparin in the treatment of unstable angina.…”

Section: Discussionmentioning

confidence: 66%

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

Leadley¹,

Kasiewski²,

Bostwick³

et al. 1998

ATVB

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Abstract-Experiments were designed to compare the antithrombotic efficacy of enoxaparin and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow reductions (CFRs) in the stenosed canine circumflex coronary artery. Low-molecular-weight heparins (LMWHs) are safe and effective in the prevention and treatment of venous thromboembolism. The present experiments were designed to evaluate the potential use of LMWHs in arterial thrombotic indications by comparing the antithrombotic effect of an LMWH with that of UH in an animal model of unstable angina. After establishment of consistent CFRs by experimentally induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was administered intravenously as a loading dose plus a continuous infusion for 1 hour. The inhibition of CFRs was taken as an indicator of antithrombotic efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose-dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kgϩ5 g/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9 to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase (NS) in template bleeding time. Near-complete abolishment of CFRs was achieved with enoxaparin at 1.0 mg/kgϩ10 g/kg per minute. This dose of enoxaparin produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL, an increase in APTT of 1.4-to 1.5-fold over baseline, and a 1.9-fold increase (PϽ0.05) in template bleeding time. In contrast, UH had no significant effect on CFRs at a dose (100 U/kgϩ10 U/kg per minute) that resulted in anti-Xa levels of 1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT greater than 10-fold over baseline, and a 2.

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Section: Discussionmentioning

confidence: 66%

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

Leadley¹,

Kasiewski²,

Bostwick³

et al. 1998

ATVB

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“…In so doing, they enhance the inhibitory effect of AT on activated factor X (FXa), thrombin (FIIa), activated FIX, and activated FXII by several orders of magnitude [1,2]. LMWHs also influence the regulation of the tissue factor (TF) pathway by releasing tissue factor pathway inhibitor (TFPI) from the endothelium, and also in part by inhibiting the generation and activity of FVIIa in an ATdependent manner [3][4][5]. The advantages of LMWHs over unfractionated heparin (UFH) are mainly because of their predictable pharmacokinetics and excellent bioavailability after s.c. administration [6], their longer half-life [7], and the lack of a need for laboratory monitoring in the large majority of patients treated [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of the anti‐factor Xa and anti‐factor IIa activities of low‐molecular‐weight heparins upon the phases of thrombin generation

Gerotziafas

Petropoulou

Verdy

et al. 2007

Journal of Thrombosis and Haemostasis

103

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To cite this article: Gerotziafas GT, Petropoulou AD, Verdy E, Samama MM, Elalamy I. Effect of the anti-factor Xa and anti-factor IIa activities of low-molecular-weight heparins upon the phases of thrombin generation. J Thromb Haemost 2007; 5: 955-62.Summary. Background: Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) by different depolymerization procedures, vary in both their relative abilities to enhance the inhibition of FXa (anti-FXa) and thrombin (anti-FIIa), and in their physicochemical properties. Objective: We aimed to profile the inhibition of thrombin generation induced by bemiparin, enoxaparin, nadroparin, dalteparin and tinzaparin in platelet-rich plasma (PRP), and to compare them with UFH and fondaparinux (a synthetic pentasaccharide that specifically enhances FXa inhibition). Methods: Different LMWHs, UFH or fondaparinux were added to normal PRP. Thereafter, tissue factor-triggered thrombin generation was assessed using the ThrombogramThrombinoscope Ò assay. Results: At equivalent anti-FIIa activity concentrations, LMWHs and UFH exhibited similar inhibitory effects upon thrombin generation. However, when used at equivalent anti-FXa activity concentrations, tinzaparin was significantly more active than the other LMWHs at inhibiting thrombin generation, and had similar activity to that of UFH. Enoxaparin, nadroparin and dalteparin all showed similar inhibitory activities. In these experiments, bemiparin exhibited the lowest inhibitory effect on thrombin generation of all the LMWHs. At 0.1 lg mL -1 (0.093 anti-FXa IU mL -1 ), fondaparinux inhibited the rate of thrombin generation by 50%. A 7-fold higher concentration of fondaparinux was required to inhibit the endogenous thrombin potential by 50%. Conclusions: LMWHs have a variable inhibitory effect on thrombin generation in vitro when compared by anti-FXa activity, but are similar when compared by their anti-FIIa activities. The rate of thrombin generation during the propagation phase, rather than the endogenous thrombin potential, is more sensitive to the anticoagulant activity of fondaparinux and the polysaccharide chains of LMWHs possessing only anti-FXa activity.

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“…16) Evidence suggests that, in addition to the anti Xa and anti IIa activities, heparin and LMWHs may exert their antithrombotic effects by stimulating the release of an endogenous tissue factor pathway inhibitor (TFPI). 5,[18][19][20] One may speculate that LMWHs may also release TFPI more efficiently than UFH owing to their higher bioavailability. Another potential mechanism by which LMWHs may exert their antithrombotic effect is through inhibition of the interaction of von Willebrand factor (vWF) with platelets resulting in reduced vWF dependent platelet adhesion and aggregation.…”

Section: Discussionmentioning

confidence: 99%

Head-to-Head Comparison of Two Different Low-Molecular-Weight Heparins in Acute Coronary Syndrome. A Single Center Experience.

et al. 2002

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SUMMARYLow-molecular-weight heparins (LMWH) of different types have yielded different results when used in the setting of unstable angina (UA) or non Q-wave myocardial infarction (NQMI). We compared the safety and therapeutic efficacy of two different LMWHs, namely dalteparin (Dalt.) and enoxaparin (Enox.), in the acute phase (first 5 days) of UA or NQMI.One hundred and forty-two patients with UA/NQMI were randomly assigned to treatment with either Dalt. [120 IU/kg twice daily by subcutaneous (SC) injection] or Enox.[1 mg/kg twice daily by SC injection]. The occurrence of any one of death, myocardial infarction, or angina recurrence within 5 days of the first LMWH injection was the endpoint of the study. There were 69 patients in the Enox. group (53 males, 16 females, mean age : 60.3±11.9) and 73 patients in the Dalt. group (54 males, 19 females, mean age : 59.6 ±10.3). The baseline characteristics of the patients in the two groups were similar. There were no deaths in either group. Myocardial infarction occurred in two patients in the Dalt. group (4%). Angina recurrence was seen in 11 patients in the Enox. group (16%) and in 11 patients in the Dalt. group (15%). Overall, any of the events that made up the endpoint occurred in 11 (16%) and 14 (19%) patients in the Enox. and Dalt. groups, respectively (P>0.05). The time to occurrence of the first event, however, was significantly longer in the Enox. group (82.3±33.2 versus 37.6±23.4 hours, P=0.007). Thrombocytopenia and allergic reactions were not detected in any patient. Major bleeding was seen in 1 patient in the Enox. group. Minor bleeding occurred in 17 (25%) and 21 (29%) patients in the Enox. and Dalt. groups, respectively (P>0.05).Enoxaparin and dalteparin were found to be equally safe and effective for the early management of UA/NQMI, but enoxaparin appeared to delay the occurrence of MI or angina recurrence as compared to dalteparin in this setting. (Jpn Heart J 2002; 43: 433-442)

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Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor

Cited by 62 publications

References 20 publications

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

Effect of the anti‐factor Xa and anti‐factor IIa activities of low‐molecular‐weight heparins upon the phases of thrombin generation

Head-to-Head Comparison of Two Different Low-Molecular-Weight Heparins in Acute Coronary Syndrome. A Single Center Experience.

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