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Letters

The end of the heparin pump?

BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7209.575a (Published 28 August 1999) Cite this as: BMJ 1999;319:575

Dosage regimens for low molecular weight heparins differ

  1. Mark Lloyd, senior registrar (mark{at}lloyd6236.freeserve.co.uk)
  1. Department of Rheumatology, St Thomas's Hospital, London SE1 7EH
  2. Royal Gwent Hospital, Newport, Gwent NP9 2UB
  3. North and East Devon Health Authority, Exeter EX1 1QT
  4. Wessex Institute for Health Research and Development, University of Southampton, Southampton SO16 7PX
  5. Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW

    EDITOR—Grubb et al's editorial reviewed the use of subcutaneous heparin; the advantages in efficacy and simplicity in the treatment of thromboembolic disease and angina now seem clear.1 A potential difficulty, which is clear in the everyday use of these agents, is the differing dosages required. Because the agents are commonly prescribed in a busy on-call setting, calculation errors are also more likely to occur. Five agents are mentioned, of which three are available in the United Kingdom. The table shows the dosage regimens for these agents.

    Dosage regimens for low molecular weight (LMW) heparins available in United Kingdom for treatment of thromboembolism and unstable angina

    View this table:

    Other agents with similar indications will probably be licensed. Perhaps it would be useful for regulatory bodies to introduce a uniform system of equivalent doses, similar to that used in insulin prescription.

    References

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    Epidural haematoma may occur after epidural and spinal regional anaesthesia

    1. Christopher C Callander, consultant anaesthetist (ceverett{at}gwent.nhs.gov.uk)
    1. Department of Rheumatology, St Thomas's Hospital, London SE1 7EH
    2. Royal Gwent Hospital, Newport, Gwent NP9 2UB
    3. North and East Devon Health Authority, Exeter EX1 1QT
    4. Wessex Institute for Health Research and Development, University of Southampton, Southampton SO16 7PX
    5. Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW

      EDITOR—In their editorial Grubb et al reviewed the advantages of low molecular weight heparins over unfractionated heparin in a variety of clinical situations and pointed out that they can be used for thromboprophylaxis in certain types of surgery.1 They urged caution when considering practical procedures such as arterial sampling and insertion of central venous lines but omitted to highlight the risk of epidural haematoma after epidural and spinal regional anaesthesia or lumbar puncture.

      Cases of life threatening expanding haematoma in the spinal canal in patients who are receiving either type of heparin have been reported.2 Members of the Food and Drug Administration in the United States have expressed concern about reports they have received on 36 patients who had spinal or epidural haematoma after receiving low molecular weight heparins in association with epidural and spinal anaesthesia.3 As a result of these reports the Food and Drug Administration has asked the manufacturers to include a “black box” warning of this potential complication in their product labelling. It has been recommended that, to minimise this complication, epidural and spinal blocks should only be started one hour before low molecular weight heparins or over 12 hours after the last dose.4

      References

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      Low molecular weight heparins have practical advantages, but clinical advantages are small

      1. Ken Stein, consultant in public health medicine (Ken.Stein{at}nedevon-ha.swest.nhs.uk),
      2. Tricia Nicholson, research assistant
      1. Department of Rheumatology, St Thomas's Hospital, London SE1 7EH
      2. Royal Gwent Hospital, Newport, Gwent NP9 2UB
      3. North and East Devon Health Authority, Exeter EX1 1QT
      4. Wessex Institute for Health Research and Development, University of Southampton, Southampton SO16 7PX
      5. Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW

        EDITOR—Grubb et al identify low molecular weight heparin as a potentially cost effective element in the management of unstable coronary artery disease.1 Several small inaccuracies in their editorial may, however, serve to overstate the quality and strength of the evidence base and add to the points made by Jefferson.2

        Grubb et al suggest that the ESSENCE study shows that enoxaparin is as effective as unfractionated heparin at preventing any of the three major outcomes (death, myocardial infarction, and recurrent angina).3 In fact, this was a composite outcome: no significant effect was shown on each of these measures individually. Also, it is wrong to say that the incidence of minor haemorrhagic complications was the same in the two groups in the trial. Altogether 11.9% of patients taking enoxaparin had minor bleeding complications, compared with 7.2% taking unfractionated heparin (P<0.001).

        Furthermore, it is wrong to say that the FRIC study4 showed that dalteparin prevents death. By day 6 (at the end of the first phase of the study) significantly more deaths had occurred in the dalteparin group than the unfractionated heparin group, although the number of events was small (11 deaths v 3 deaths; relative risk 3.37 (95% confidence interval 1.01 to 11.24)).

        Using low molecular weight heparins has undoubted practical advantages, but the clinical advantages they offer are small. What is not clear is whether the savings that theoretically might be made alongside clinical benefits can be realised in practice, either within cardiac care services or to allow investment in other areas.

        References

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        Author's reply

        1. Neil Grubb, ecturer in cardiology
        1. Department of Rheumatology, St Thomas's Hospital, London SE1 7EH
        2. Royal Gwent Hospital, Newport, Gwent NP9 2UB
        3. North and East Devon Health Authority, Exeter EX1 1QT
        4. Wessex Institute for Health Research and Development, University of Southampton, Southampton SO16 7PX
        5. Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW

          EDITOR—There is certainly potential for confusion about doses of low molecular weight heparins, and my colleagues and I appreciate Lloyd's clarification of these. We would emphasise that low molecular weight heparins should be prescribed only for indications for which the agent is proved and licensed, as shown in the table that Lloyd provides. For instance, not all low molecular weight heparins are necessarily effective for unstable angina. Callander's comments in his letter highlight a potentially dangerous complication of low molecular weight heparins in patients undergoing epidural or spinal anaesthesia.

          Stein and Nicholson raise some points that require clarification. Firstly, we agree that the ESSENCE trial's primary end point was the composite of death, myocardial infarction, or recurrent angina at 14 day follow up. Enoxaparin plus aspirin was superior to unfractionated heparin plus aspirin with respect to this end point. For each of the individual end points, outcomes were not shown to be superior Secondly, we wrongly stated that enoxaparin was associated with a similar rate of minor haemorrhagic events in that trial. Mainly as a result of bruising at the injection site, enoxaparin was associated with a significantly higher rate of these events. We apologise for making this clear error. Thirdly, in the FRIC study, the primary outcomes included death after the prolonged treatment phase, not the acute phase. For this time point the death rate was identical in the dalteparin and unfractionated heparin groups (2%).

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