Anticoagulation may be beneficial in high risk factor V Leiden carriers

BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7155.416 (Published 08 August 1998) Cite this as: BMJ 1998;317:416
  1. Trevor Baglin, Consultant haematologist,
  2. Caroline Baglin, Clinical nurse specialist,
  3. Karen Brown, Senior technologist,
  4. Roger Luddington, Chief technologist,
  5. East Anglian Thrombophilia Study Group
  1. Clinical Haematology, Box 234, Addenbrooke's NHS Trust, Cambridge CB2 2QQ

    EDITOR—Sarasin and Bounameaux's decision analysis model of treatment in factor V Leiden carriers1 is in keeping with the results of our cohort study.2 In our study the annual rate of recurrence when treatment with warfarin was stopped was 11.1 per 100 patient-years. Patients who had an idiopathic first event were more likely to have a recurrence than those whose first event was precipitated (log rank=4.76, P=0.029). The recurrence rate in these high risk patients was 28.6 per 100 patient-years.

    In a previous prospective cohort study of patients who had had a first deep vein thrombosis 11.5% of recurrent events were fatal, but all deaths occurred in patients with cancer.3 In the absence of cancer the risk of fatal recurrence was zero after a median follow up of nearly eight years. Even if 1% of events are assumed to be fatal in the absence of cancer, our study indicates that the risks of fatal haemorrhage and thrombosis would be roughly equivalent (0.28 v0.25 deaths per 100 patient-years).

    However, the aim of treatment is not only to prevent death but to prevent recurrence of non-fatal venous thromboembolism. Recurrence is associated with acute pain and venous obstruction and an increased risk of the post-phlebitic syndrome, itself a risk factor for further thromboembolism. Extended oral anticoagulant therapy may therefore be beneficial, particularly in high risk patients with idiopathic first events. Our study indicates that oral anticoagulation with a target international normalised ratio of 2.5 is effective in reducing the risk of recurrence but that after the initial six months of treatment the benefit: risk ratio is reduced.A lower intensity of long term anticoagulation should now be evaluated in a large prospective study.

    Maintaining a lower international normalised ratio may lower the risk of haemorrhage while still preventing acute recurrent events. This may reduce a small risk of death but also a large risk of progressive morbidity due to the post-phlebitic syndrome. It seems feasible that such treatment would be effective since low dose warfarin regimens have been shown to be effective in other groups of high risk patients. 4 5


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