[Therapeutic indications of low molecular weight heparins]

Abstract

The depolymerisation of the various chains of unfractionated heparin (UFH) by chemical or enzymatic reactions provides so-called low molecular weight heparin (LMWH), with an average molecular weight of approximately 5000 daltons. The specific biological and pharmacokinetic properties of LMWH with greater inhibition of factor Xa than of thrombin activity, less interaction with platelets, better bioavailability and a longer half life of anti-Xa activity, suggest possible new therapeutic applications. The hypothesis of reducing the risk of haemorrhage related to the antithrombin activity and the incidence of heparin-induced thrombocytopenia whilst preserving effective antithrombotic action has stimulated clinical and biological research. Clinical trials of prophylaxis of venous thrombo-embolism have been undertaken mainly in surgical patients. The results have shown identical if not better efficacy of LMWH compared to UFH in general surgical and above all orthopedic patients in whom subcutaneous heparin is only effective with a strict protocol which is difficult to adhere to in routine practice (adaptation of dosage to activated partial thromboplastin time). The risk of bleeding was not significantly lower using LMWH at the specified dosage, which in the latter indication, is twice that used in general surgery. There are many indications of prophylaxis of thromboembolism in the medical specialties but, paradoxically, LMWH has not been widely studied because of the difficulties in performing the therapeutic trials. Except in rare cases (extreme body weights, renal failure, haemorrhagic disease, thrombotic or haemorrhagic complications) the evaluation of amidolytic anti-Xa activity does not seem to be necessary. More recently, LMWH has been studied in a small number of trials for the treatment of deep venous thrombosis (DVT). The therapeutic efficacy is identical if not better than that of UFH without increasing the risk of bleeding. Biological monitoring seems to be necessary in this indication for evaluating amidolytic anti-Xa activity, which, though not a true marker of antithrombotic activity is a relatively sensitive investigation. The therapeutic values are 0.5 IU/ml to 1.0 IU/ml, 3 to 4 hours after subcutaneous injection. The conclusions of all these trials are: LMWH is relatively simple to use and, compared with UFH, has a more stable anticoagulant effect due to its pharmacokinetic properties; the therapeutic efficacy is as good as, if not better, than that of UFH; the risk of bleeding remains, therefore, the specified dosages should be respected and treatment should be monitored by anti-Xa activity when indicated; the decreased interaction with platelet function should not mask the risk of thrombocytopoenia.(ABSTRACT TRUNCATED AT 400 WORDS)