An International Standard for Low Molecular Weight Heparin

Barrowcliffe, T W; Curtis, A. D. M.; Johnson, Edward A.; Thomas, Duncan P.

doi:10.1055/s-0038-1647623

Cited by 83 publications

(35 citation statements)

References 6 publications

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“…Following a preliminary study, two of eight LMWHs were identified as giving the least inter-laboratory variability when used as a standard for assay of the other preparations, with CVs in the range of 4-14% (47). These two preparations were then subjected to a large international collaborative study, and one of the materials was established by WHO as the 1 st International Standard for LMWH in 1986 (48). Although WHO Standards are traditionally assigned a single potency, this would have been inappropriate in the case of LMWH, because of the large difference between potencies by anti-Xa and anti-IIa assays (around 2.5 fold).…”

Section: Measurement Of Anticoagulant Activitiesmentioning

confidence: 99%

Heparin and low-molecular-weight heparin

Mulloy,

Barrowcliffe,

Gray

2008

Thromb Haemost

235

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SummaryHeparin is one of the oldest biological medicines, and has an established place in the prevention and treatment of venous thrombosis. Low-molecular-weight heparins (LMWH) have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of adminisKeywords Heparin, low-molecular-weight heparin tration. They have been shown to be at least as effective and safe as unfractionated heparin and have replaced the latter in many indications. In this article the chemistry, mechanisms of action, measurement of anticoagulant activities, and clinical status of heparin and LMWH are reviewed.

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Section: Measurement Of Anticoagulant Activitiesmentioning

confidence: 99%

Heparin and low-molecular-weight heparin

Mulloy,

Barrowcliffe,

Gray

2008

Thromb Haemost

235

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“…The standard of choice for calibration of anti-Xa assays for monitoring LMWH therapy should therefore be a LMWH that has been calibrated against the 1st WHO International Standard for LMWH (Barrowcliffe et al, 1988).…”

Section: Monitoring Low Molecular Weight Heparin Therapymentioning

confidence: 99%

Problems In Laboratory Monitoring Of Heparin Dosage

Kitchen

2000

Br J Haematol

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“…The latter effect is especially important in the case of human factor Xa, and the extent of this effect depends on the heparin molecular size. In addition, the anti-factor Xa and anti-thrombin activities assayed are expressed relative to those of a UF reference preparation (U/mg), of which the anti-factor Xa and antithrombin activities are per definition equal, or relative to a LMW reference preparation which has been calibrated against the UF reference preparation (Barrowcliffe et al, 1988). This approach tends to obscure the fact that in practice thrombin is inhibited much faster than factor Xa.…”

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confidence: 99%

Ratios of anti‐factor Xa to antithrombin activities of heparins as determined in recalcified human plasma

Schoen¹,

Lindhout

Hemker

1992

Br J Haematol

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Summary. Anti-factor Xa and anti-thrombin activities of unfractionated (UF) and low molecular weight (tMW) heparins have been measured in human plasma and with purified human antithrombin III (ATIII) in the absence and presence of 1'5 mu calcium. The anti-factor Xa and antithrombin activities were measured directly, by assessing the heparin-dependent pseudo-first order rate constants of inactivation of human factor Xa or thrombin. These activities were studied with the 4th International Standard for UF heparin, the lst International Standard for LMW heparin, C'1216, enoxaparin, Cy222, and the synthetic pentasaccharide' In plasma, calcium equally well increased the specific antifactor Xa catalytic activities as compared to purified ATIII' That is, 1 '5 mu calcium stimulated the UF standard heparincatalysed inactivation of factor Xa 2'L-2'4 times' In the presence of the LMW heparins the effect of calcium was smaller (1 '3-1 '7 times), and in plasma there was no effect of calcium on the pentasaccharide-catalysed inactivation of factor Xa. Thus, the largest effects of calcium in the inactivation reaction of factor Xa is seen with UF standard heparin. Calcium reduced the anti-thrombin activities of all the heparin preparations studied about 1'5 times when purified ATIII was used, although in plasma this effect was less clear. Consequently, in the presence of 1'5 mlu calcium the ratio of the anti-factor Xa to the anti-thrombin activities of UF standard heparin approximated those of the LMW heparins. The only exception was CY222, which under all conditions retained anti-factor Xa/anti-thrombin ratios significantly higher than those ofUF standard heparin' One of the regulatory mechanisms of blood coagulation is the inhibition of enzymes of the coagulation system by the plasma protein antithrombin III (ATIII)' its main targets in clotting plasma being thrombin and factor Xa (Harpel' 1987). Inactivation ofthese serine proteases is catalysed by heparin, and thus the heparin-dependent anti-factor Xa and anti-thrombin activities have become main points of interest in studying the mode of action and the standardization of heparin. It should also be noted here, however, that the ATlll-dependent inactivation of free factor fXa can contribute significantly to the heparin effect in clotting plasma (B6guin et al, l99l).Since 1976 it is known that low molecular weight (LMW) heparin fractions have little effect on tests of overall clotting' such as the activated partial thromboplastin time (APTT)' but + Present address:

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An International Standard for Low Molecular Weight Heparin

Cited by 83 publications

References 6 publications

Heparin and low-molecular-weight heparin

Heparin and low-molecular-weight heparin

Problems In Laboratory Monitoring Of Heparin Dosage

Ratios of anti‐factor Xa to antithrombin activities of heparins as determined in recalcified human plasma

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