A Standard for Low Molecular Weight Heparin?

Hemker, H.C.

doi:10.1159/000215881

Cited by 15 publications

(9 citation statements)

References 5 publications

(5 reference statements)

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“…The present results indicate the importance of the antifactor Xa activity of heparins for the expression of their antithrombotic effects as suggested and discussed in recent reports (Tew et a/, 1988;Cadroy et al, 1989;Lane & Ryan, 1989). They must be taken into account in the controversies concerning the problem of the standardization of LMWH currently based upon the antifactor Xa activity (Ofosu et a/, 1988a: Hemker, 1989Thomas & Barrowcliffe, 1989). ledge J. Choay, J. C. Lormeau a n d M. Petitou (Sanofi-Choay) for providing the heparins tested i n these studies.…”

Section: Discussionmentioning

confidence: 99%

Antithrombotic potencies of heparins in relation to their antifactor Xa and antithrombin activities: an experimental study in two models of thrombosis in the rabbit

Amar¹,

Caranobe²,

Sié³

et al. 1990

Br J Haematol

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Our purpose was to determine the relative contribution of the antifactor Xa and antithrombin activities of heparin to its antithrombotic potency. The antithrombotic activities of unfractionated heparin (UH), two low molecular weight heparins (LMWH, CY 216 and CY 222) with increasing anti-factor Xa/antithrombin ratio and a synthetic pentasaccharide (PS) with high affinity to antithrombin III and no antithrombin activity were evaluated. In the Wessler-thromboplastin model, the most potent antithrombotic agent, on a weight basis, was UH followed by CY 216, CY 222 and the PS which was 40 times less potent than UH. On an antithrombin unit basis, the antithrombotic potencies of UH, CY 216 and of CY 222 were equivalent. Thus, in this model, the antithrombotic effect results from the catalytic action of UH or LMWH on thrombin inhibition. In the Wessler-serum model, on a weight basis, the antithrombotic effectiveness of UH was unchanged, those of CY 216 and CY 222 were doubled, and that of the PS was increased 10 times. On an anti-factor Xa unit basis, CY 216 was as effective as UH, and PS as effective as CY 222. On an antithrombin unit basis, CY 216 and CY 222 were equivalent and more potent than UH. Thus, in this model, the antifactor Xa activity of heparin becomes important for its antithrombotic property. After a single subcutaneous injection of 1000 antifactor Xa U/kg, the antithrombotic effects of UH were maintained for more than 14 h in the two models. After injection of the same dose of CY 216 significant antithrombotic effects were observed only for 9 h, in the Wessler-thromboplastin model but for 18 h in the Wessler-serum model. At that time, no detectable antithrombin activity was measurable in the plasma while 0.11 units of antifactor Xa activity/ml was detected. Thus, the relative contribution of the anti-factor Xa and antithrombin activities to the antithrombotic effect of a LMWH differs according to the nature of the thrombogenic stimulus.

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Section: Discussionmentioning

confidence: 99%

Antithrombotic potencies of heparins in relation to their antifactor Xa and antithrombin activities: an experimental study in two models of thrombosis in the rabbit

Amar¹,

Caranobe²,

Sié³

et al. 1990

Br J Haematol

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“…Their conclu sion was that the antithrombotic activity of LMWH is not directly related to its subfrac tion, catalysing thrombin inhibition. These results indicate that 'it would be an over-sim plification to attribute the antithrombotic ac tivity of LMWH primarily to any of its spe cific subfractions' [28].…”

Section: Discussionmentioning

confidence: 91%

“…At present there is a contro versy about the question to what extent anti factor Xa activity reflects the biological anti thrombotic effect. Earlier it has been argued that inhibition of factor Xa consequently more effectively prevents thrombin forma tion than direct thrombin inhibition [26], However, recent data shown that the contrary is true and that the inhibition of prothrombin activation minimally contributes to the over all effect on thrombin formation [27], Anti factor Xa activity is probably more of an 'epiphenomenon' [28] as the effect on endothe lium, fibrinolysis, platelets etc. is also of im portance in vivo [7], In contrast to the results from production methodology [21][22][23], Doutremepuich et al [29] studied several LMWHs given on an equivalent weight basis (1 mg/kg) in vitro and in an in vivo vena cava model in rats and found variations in activity in vivo as well as in vitro.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Experimental Venous Thrombosis in Rabbits with Different Low Molecular Weight Heparins, Dermatan Sulphate and Hirudin

Matthíasson

Lindblad²,

Bergqvist³

1995

Pathophysiol Haemos Thromb

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In a randomized, blind study the antithrombotic efficacy of dermatan sulphate (DS), recombinant hirudin (r-hirudin) and four commercially available low molecular weight heparins (LMWHs) was investigated after intravenous administration in a jugular vein thrombus model in rabbits utilizing a combination of endothelial damage and flow reduction. The parameters observed were the frequency of visible thrombosis, the frequency of occlusive thrombosis and thrombus weights. DS and r-hirudin were investigated in one fixed dose and the LMWHs in prophylactic doses, adjusted to body weight, recommended in high-risk situations by the manufacturers. All substances effectively reduced the three observed parameters. DS and r-hirudin were equally or even more effective than the LMWHs. Although significant differences were not found between the individual LMWH treatments a visible trend cannot be overlooked in all three observed parameters. This cannot solely be explained by the different antifactor Xa activity doses given but increased antithrombotic activity was observed with declining antifactor Xa/antifactor Ila ratio. Our findings indicate that the different commercial LMWHs may differ in their antithrombotic activity when given in recommended doses adjusted to body weight in this experimental model. Dose range studies are required to clarify the thrombo-prophylactic efficacy of DS and r-hirudin in relation to the tested LMWHs.

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“…Institut Choay-Sanofi, Gentilly, France Dear Sir, Following a recent debate published in this journal [1], it appears that the question of the usefulness of a low molecular weight (LMW) heparin standard has still to be set tled. Jointly, measurement of the Anti-Xa (AXa) activity as the main parameter to be monitored in patients is strongly proposed [2], without evidence.…”

Section: F Toulemondementioning

confidence: 99%

Is the Problem of the International Standard for Low Molecular Weight Heparin Crucial for the Clinician?

Toulemonde

1990

Pathophysiol Haemos Thromb

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A Standard for Low Molecular Weight Heparin?

Cited by 15 publications

References 5 publications

Antithrombotic potencies of heparins in relation to their antifactor Xa and antithrombin activities: an experimental study in two models of thrombosis in the rabbit

Antithrombotic potencies of heparins in relation to their antifactor Xa and antithrombin activities: an experimental study in two models of thrombosis in the rabbit

Prevention of Experimental Venous Thrombosis in Rabbits with Different Low Molecular Weight Heparins, Dermatan Sulphate and Hirudin

Is the Problem of the International Standard for Low Molecular Weight Heparin Crucial for the Clinician?

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