HAEMOSTASIS
Anticoagulants’. Professor Patrick Mismetti (St Etienne, France) spoke in favour of the motion, Dr Menno Huisman (Leiden, The Netherlands) spoke against, and Prof. Brian Colvin (London) moderated. A straw poll of delegates taken before the debate showed that a significant majority agreed with the motion. Several new oral anticoagulants (e.g. dabigatran, rivaroxaban, apixaban) now seem set to challenge the dominance of the vitamin K antagonists (e.g. warfarin). One of the perceived overriding advantages of this new generation of drugs is that there is no requirement for laboratory monitoring. Dr Mismetti argued that this perception may be flawed and that while unmonitored use is appropriate in most cases, monitoring and subsequent dose adjustment may be warranted in a significant number of patients or situations such as liver disease, renal failure, advanced age or when co-prescribed with one of a few specific drugs. He suggested monitoring may also be appropriate when patients are bleeding, have recurrent on-treatment thrombosis or prior to any invasive procedures. Dr Huisman argued that the available evidence does not support laboratory monitoring, the anticoagulant effect of a fixed dose is highly predictable, there is no evidence that bleeding or antithrombotic effect correlates with any related biological activity, and that the safety of fixed doses has been demonstrated in many thousands of patients in clinical trials. It should also be noted that, while it has been shown that the new drugs do affect a number of laboratory tests of haemostasis, as yet the relationship between any test result and the level of drug and its therapeutic effect has not been demonstrated satisfactorily. Dr Huisman emphasised the distinction between ‘monitoring’ and ‘measuring’: monitoring implies that the dose of drug is regularly adapted according to the result of an appropriate test, while measuring implies simple quantitation only. He did accept that measurement may occasionally be informative. A repeat straw poll at the end of the debate showed a slight swing against the motion, but if the original proposal was reworded with ‘measuring’ substituted for ‘monitoring’ then all delegates thought this was desirable.
Atrial fibrillation The morning session of the second day concluded with a presentation by Dr Campbell Tait (Glasgow) on Anticoagulation in the Management of Atrial Fibrillation. It is estimated that about 1% of the adult population has atrial fibrillation, the incidence increasing with age, rising to a figure of about 8% of the population aged 75 or over. The
32 THE CLINICAL SERVICES JOURNAL
Traumatic birth, forceps or Ventouse delivery, prolonged second-stage labour and prematurity are all associated with an increased risk of bleeding, and the use of short-term prophylaxis in these situations is generally recommended.
presence of atrial fibrillation is associated with an approximate five-fold increase in stroke. This can be significantly reduced (by some 60%) using well-controlled treatment with vitamin K antagonists (e.g. warfarin). Several scoring systems are available to assess the risk of stroke in patients with atrial fibrillation, the latest of which, as recommended by the European Society of Cardiology, is the CHA2
DS2 -
VASc system, which considers cardiac failure, hypertension, age, diabetes, previous stroke or thrombosis, vascular disease and gender. If it becomes widely adopted, it is estimated that about 95% of patients with atrial fibrillation will be considered eligible for anticoagulation, assuming there are no specific contraindications or high risk of bleeding. However, before a decision to commence warfarin is made, these factors, together with the problems associated with warfarin monitoring and the many factors that affect dose response, need to be very carefully considered. Given the facts that warfarin treatment is associated with an increased risk of bleeding and that its management is not easy, particularly for many elderly patients, any new drug of equivalent efficacy that lessens these problems would be beneficial. The new generation of oral anticoagulants that do not normally require monitoring show some initial promise and they may potentially have a future role in this setting.
Haemophilia inchildren The final session of the meeting was chaired by Professor IsobelWalker (UK NEQAS BC scheme director), who welcomed Dr Mike Richards (Leeds) to present Challenges in the Management of Haemophilia in Children. The management of severe haemophilia in infants and children is challenging, not always based on strong evidence, and may have a lifelong impact on patients and their families. Consequently, it should always be undertaken in, or under the close supervision of, specialist units with the appropriate expertise and experience. Traumatic birth, forceps or Ventouse delivery, prolonged second-stage labour and prematurity are all associated with an increased risk of bleeding, and the use of short-term prophylaxis in these situations is generally recommended. Subsequently, the overall aim of treatment is to reduce the number of bleeds, reduce joint damage and improve the quality of life. The latest evidence suggests that this is best achieved by the early introduction of prophylactic treatment with clotting factor concentrates commencing under the age of three years. Details of recommended prophylactic regimes, in respect of when to initiate treatment and its magnitude and frequency, vary from country to country and will be influenced by the clinical picture in individual cases. When compared to an ‘on-demand’ treatment approach, prophylaxis may suggest an increased consumption of factor concentrates and consequently increased cost. Studies in young adult patients have, however, shown this not to be the case, with no difference in annual consumption between the two groups. A prophylactic approach may indeed have economic benefits associated with reduced arthropathy and improved quality of life. There is some evidence that prophylaxis may also be associated with reduced development of factor VIII antibodies.
Recombinant factor VIII Monitoring Post-Infusion Factor VIII Levels was discussed in the next presentation given by Dr Steve Kitchen (Sheffield). Several different recombinant factor VIII concentrates that are used to treat haemophiliacs are commercially available. Following infusion of one of these products, it is important for
‘The presence of atrial fibrillation is associated with an approximate five-fold increase in stroke. This can be significantly reduced (by some 60%) using well-controlled treatment with vitamin K antagonists such as warfarin’.
MARCH 2012
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