The disappearance of a low molecular weight heparin fraction (cy 216) differs from standard heparin in rabbits

Boneu, B; Mr, Buchanan; Caranobe, C; Am, Gabaig; Dupouy, D.; Sié, P.; Hirsh, Jack

doi:10.1016/0049-3848(87)90076-4

Cited by 37 publications

(20 citation statements)

References 11 publications

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“…In view of the results reported by other authors using LMWH in hemodialysis, the advantage of Fraxiparin is its use as a single intravenous bolus injection at the start of the session whereas an additional continuous in fusion is usually recommended with UFH [3,16,[20][21][22][23]. This is due to a greater half-life of Fraxiparin as compared to standard heparin.…”

Section: Discussionmentioning

confidence: 81%

“…However, a com parison of the AXa activities that we ob served with those reported by other authors is not presently possible since there is no common standard for LMWH. This is why our AXa activity curve was calibrated against Fraxiparin rather than against UFH as several authors did [18][19][20], AH that clearly shows that it is not necessary to ad just Fraxiparin doses or to monitor blood Fraxiparin levels by means of AXa activity measurements.…”

Section: Discussionmentioning

confidence: 99%

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Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Morinière

Dieval²,

Bayrou³

et al. 1989

Blood Purif

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A two-step dose-ranging study was undertaken with CY216 (Fraxiparin®) in 8 patients on 7 sessions each. The different doses were administered each time as a single bolus injection at the start of hemodialysis without heparinized priming nor further administration during the 4-hour session. In the first step, the clinical efficacy of 4 different doses of Fraxiparin was compared with that of standard heparin on the percentage of sessions free of clot formation in the extracorporeal circulation (ECC). Safety was evaluated by the compression time for hemostasis at the puncture sites. The second step was a randomized comparison of 3 Fraxiparin dosages. In addition to the clinical assessment of efficacy, the following biological parameters were measured: fibrinopeptide A (FPA), anti-Xa (AXa) activity calibrated against Fraxiparin, thrombin time (TT), activated partial thromboplastin time, blood counts, hemoglobin, hematocrit, plasma creatinine and urea, and residual blood volume in the dialyzer. A ‘standard’ dosage of 10,000 AXa Institut Choay units of Fraxiparin was shown to prevent clot formation in the ECC. It resulted in a marked increase in TT, without any lengthening of the puncture site compression time. After 4 h, AXa and FPA levels in the venous line were related to the doses used (p < 0.05). After 48 h AXa activity was very low. Dialysance and tolerance were excellent. Thus, a single dose of Fraxiparin unrelated to body weight and not determined by the measurement of the whole-blood activated clotting time appeared to be a safe and effective means for preventing fibrin formation in 4-hour dialysis sessions.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Morinière

Dieval²,

Bayrou³

et al. 1989

Blood Purif

View full text Add to dashboard Cite

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“…The necessity or otherwise for laboratory monitoring of LMWH is not yet established (Boneu, 1994). However, as the interpatient variability in dosage requirements is much lower for LMWH (Handeland et al, 1990) than for UF heparin and as the half-life of LMWH (unlike UF) is essentially independent of dose (Boneu et al, 1987), it is improbable that laboratory monitoring of LMWH will need to be as frequent as for UFH. This is supported by a prospective randomized trial in which a fixed dose (100 iu/kg) was compared to a dosage adjusted by anti-Xa activity to obtain a target of 0´5±1´0 iu/ml (Alhenc-Gelas et al, 1994).…”

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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“…This is corrob orated by the finding of an identical apparent pharmacological half-life time for the ACLM after subcutaneous injection of either LMWH or UFH [8]. It is well known that the half-life time of a heparin varies strongly with the molecular size [10,42], Identical half-life times suggest that the MW distribution of the ACLM in the blood after injection of UFH is similar to that after injection of LMWH.…”

Section: Lm W H S Are Likely To Lack a Haem Orrhagic Com Ponent Presementioning

confidence: 81%

Can the Haemorrhagic Component of Heparin Be Identified? Or an Attempt at Clean Thinking on a Dirty Drug

Hemker¹,

Béguin²,

Kakkar³

1996

Pathophysiol Haemos Thromb

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Heparin consists of different classes of molecules. We distinguish below-critical-chain length heparin (BCLM, MW <5,400), with only anti-factor Xa activity and above-critical-chain length material (ACLM, MW > 5,400) with both antithrombin and anti-factor Xa activity. In this article we introduce a division within the ACLM fraction, between extra large material (MW >8,000) and ACLM-low (MW 5,400-8,000). Extra large material is abundantly present in unfractionated heparin but is rare in low-molecular-weight (LMW) heparins. We noted that injection of an LMW heparin causes 5- to 10-fold higher plasma levels of ACLM than injection of a clinically equivalent dose of unfractionated heparin (UFH) and proportionally higher inhibitions of the clotting system. So with LMW heparin one can afford higher levels of anticoagulation than with UFH at a lower risk of bleeding. We surmise that this is caused by the virtual absence of the (haemorrhagic) extra-large-molecular-weight fraction from LMW heparins. A laboratory artefact, i.e. the absence of Ca²⁺ in the anti-factor Xa tests, makes that heparin mixtures that lack extra large heparin molecules show a (spuriously) high ratio of anti-factor Xa activity over anti-thrombin activity. So the correlation between a high aXa/alla ratio and a favourable ratio of antithrombotic effect over bleeding is not necessarily caused by the presence of BCLM. In fact BCLM is a poor anticoagulant; in mixtures of ACLM and BCLM, ACLM causes by far the larger part of the anticoagulant effect. We surmise that the LMW fraction of ACLM is the active anticoagulant component in any heparin preparation and, isolated, would make a proper third-generation heparin.

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The disappearance of a low molecular weight heparin fraction (cy 216) differs from standard heparin in rabbits

Cited by 37 publications

References 11 publications

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Problems In Laboratory Monitoring Of Heparin Dosage

Can the Haemorrhagic Component of Heparin Be Identified? Or an Attempt at Clean Thinking on a Dirty Drug

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