Treatment of Deep Venous Thrombosis with a Very Low Molecular Weight Heparin Fragment (CY 222)

Janvier, G.; Winnock, S; Dugrais, G; Vallet, A.; Dardel, E.; Serise, J.-M.; Calen, S.; Vergnes, C.; Toulemonde, F

doi:10.1159/000215558

Cited by 13 publications

(16 citation statements)

References 8 publications

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“…The successful clinical use of heparin and its LMW derivatives necessitates moni toring of their activities with sensitive labo ratory assays [9][10][11][12], Heparin is usually measured by aPTT and TCT tests. Because heparin possesses both anti-Xa and anti-IIa activities, it can also be quantitated in plasma by chromogenic substrate methods involving the inhibition of extraneous fac tor Xa or thrombin.…”

Section: Discussionmentioning

confidence: 99%

“…LMW heparins are currently tested for prophylaxis and treatment of thromboembo lism [9][10][11][12], LMW heparins specifically in hibit factor Xa by binding to antithrombin III. In contrast, aPTT and thrombin are inac tivated poorly by these agents [13].…”

Section: Introductionmentioning

confidence: 99%

“…Using thrombelastography, LMW heparin demonstrates a weak anticoagulant effect on recalcified whole blood [12]. On the other hand, factor Xa spe cific peptide substrate assays or coagulation tests are sensitive to LMW heparins [9][10][11][12][13][14]. Thus, the usefulness of the various coagula tion assays has to be established for clinical application of LMW heparins.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Study on a New One-Stage Clotting Assay for Heparin and Its Low Molecular Weight Derivatives

Harenberg¹,

Giese²,

Knödler³

et al. 1989

Pathophysiol Haemos Thromb

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The effects of a normal and a low molecular weight (LMW) heparin fraction were compared by four coagulation methods. Plasma samples of patients were investigated who were treated with normal heparin or with a LMW heparin. The study was undertaken to analyze the interrelationship between the coagulation methods: Heptest, activated partial thromboplastin time, thrombin clotting time, and S 2222 chromogenic anti-factor Xa test. The results showed a high correlation between Heptest and S 2222 anti-factor Xa method for unfractionated and LMW heparin (r = 0.91 and 0.90). Comparing the coagulation times in seconds of Heptest and aPTT, the correlations were r = 0.56 (normal heparin) and 0.15 (LMW heparin). The correlation between the coagulation times of Heptest and thrombin clotting time were r = 0.65 and 0.25, respectively. The correlations between the coagulation methods were higher, when coagulation times rather than transformed values to units per liter of the Heptest and of the S 2222 anti-factor Xa method were employed. Furthermore, the data demonstrate a high sensitivity of the Heptest to conventional and LMW heparin, whereas activated partial thromboplastin time and thrombin clotting time are less sensitive to either heparin. For laboratory control of LMW heparin, Heptest and S 2222 chromogenic method are reliable tests. Therapeutic ranges will have to be established.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Study on a New One-Stage Clotting Assay for Heparin and Its Low Molecular Weight Derivatives

Harenberg¹,

Giese²,

Knödler³

et al. 1989

Pathophysiol Haemos Thromb

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“…This activator binds to the thrombus immediately after its release and cannot be detected. 21 For CY 222, three test types can be identified: (1) In unmodified tests, antithrombotic activity was observed in vivo: APTT, TCT; (2) In modified tests, no statistical correlation to antithrombotic effect: Anti-Xa (HPT, HPC); t-PA. Still, the noncorrelation of t-PA can be an artifact insofar as a recent study 21 has shown that circulating t-PA can rapidly absorb to clots and then becomes undetectable;…”

Section: Discussionmentioning

confidence: 99%

“…24 ± 6 0.08 ± 0.08 0.08 ± 0.07 0.08 ± 0.08 0.08 ± 0.08 77 ± 28 0.80 ± 0. 21 12 ± 1 *Selection criteria, thrombus weight.…”

Section: Linear Correlationmentioning

confidence: 99%

Laboratory Control of Heparin and Heparin Fragment Treatment: An Experimental Study

Doutremépuich¹,

Lalanne²,

Guyot³

et al. 1989

Semin Thromb Hemost

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Native heparin is an heterogeneous substance with molecular weight between 2000 and 30,000 d. Low molecular weight heparin (LMWH) obtained after chemical and enzymatic reactions from unfractionated heparin 1,2 has low anticoagulant effect, but high antithrombotic activity, which may be higher than standard heparin activity. 3-5 Until now, plasmatic anti-Xa activity was the only biologic test used to control LMW heparin therapeutic activity in humans. However, researchers have recently demonstrated that LMW heparin antithrombotic effect was not correlated to plasmatic anti-Xa activity. [6][7][8][9][10][11] In view of the very interesting prospects offered by the LMWH therapeutic advantages, 4,12-15 it was necessary to determine which biologic test best adapted to reflect the ex vivo antithrombotic activity of fractions and, then, to give a better clinical control. MATERIAL AND METHODSThe heparin and LMWH used included, unfractionated heparin (Calciparine lot 301.1 176 USP/mg, 170 ICU/mg) and LMWH (CY 222, lot 81.051 DP, 25 USP/mg, 250 ICU mg), with a molecular weight 2500 d. These drugs were obtained from Institut Choay (Paris, France), and their activities established from standard curves (3rd heparin standard, WHO).The placebo used was isotonic saline solution. Animals (n = 198) were Wistar male rats from Janvier Breeding Center (Berthevin, France). Mean weight was 250 gr. Experimental venous thrombosis 16-18 was induced as follows: After fasting for 12 hours, the rats were anesthetized subcutaneously by ketamine injection (100 mg/kg body weight). The inferior vena cava was dissected free, and a ligature was applied just below the left renal venous branch at time zero. Two hours after ligature the two products to be tested were randomly administered: four heparin groups, four CY 222 groups, and one placebo group. Each group included 22 rats. The different dosages tested were: 4, 2, 1, and 0.5 mg/kg body weight, and 1 ml saline solution was injected as placebo.At 6 hours, the rats were anesthetized again. After intracardiac blood sampling, plasma was prepared from 9% citrated blood for ex vivo study. Then the thrombi were extracted.After sampling, each thrombus was placed in a drying cupboard at 40°C for 24 hours. Then the dried clot was weighed.Biologic activity was tested with different methods and compared with the standard curve established from the 3rd international heparin standard (WHO): activated partial thromboplastin time (APTT; CK Prest, Stago, Asnieres, France); Anti-Xa (Heptest [HPT], Haemachem, St. Louis, MO; Hepaclot [HPC], Stago; chromogenic method [SUB] CBS 31.39 Stachrom Heparin, Stago); Anti-IIa (chromogenic method [SUB] CBS 34.47 Hepachrom Ha, Stago). The method 19 for the measurement of fibrinolytic activity was as follows:1. Preparation of euglobulin solution: lots prepared from each animal's plasma were suspended in 1.5 ml of distilled water, then kept at 4°C for 10 minutes after

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A Meta-analysis Comparing Low-Molecular-Weight Heparins With Unfractionated Heparin in the Treatment of Venous Thromboembolism

Dolovich¹,

Ginsberg²,

Douketis³

et al. 2000

Arch Intern Med

448

201

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Low-molecular-weight heparins are at least as effective as UFH in preventing recurrent VTE. It is unlikely that LMWHs are superior in the treatment of VTE, but they do show a statistically significant decrease in total mortality. No differences were seen in the development of recurrent VTE dependent on treatment setting. There were no apparent differences between once-daily and twice-daily therapy or among products. Inpatient therapy may be associated with less major bleeding; therefore, if LMWHs are given in the outpatient setting, patients should be rigorously monitored.

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Treatment of Deep Venous Thrombosis with a Very Low Molecular Weight Heparin Fragment (CY 222)

Cited by 13 publications

References 8 publications

Comparative Study on a New One-Stage Clotting Assay for Heparin and Its Low Molecular Weight Derivatives

Comparative Study on a New One-Stage Clotting Assay for Heparin and Its Low Molecular Weight Derivatives

Laboratory Control of Heparin and Heparin Fragment Treatment: An Experimental Study

A Meta-analysis Comparing Low-Molecular-Weight Heparins With Unfractionated Heparin in the Treatment of Venous Thromboembolism

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