RESISTANCE TO ACTIVATED PROTEIN-C AS A PA THOGENIC FACTOR OF THROMBOPHILIA

The proportion of identifiable causes of familial thrombophilia has in creased from 5-10% to 60-70% since the identification of activated pro tein C resistance (aPCR) in February 1993 by Dahlback et at. A mutatio n in the factor V gene (C --> A, 1691) leads to the so called Leiden m utation (R 506 Q) that produces a mutated factor V resistant to the ca talytic action of activated protein C (aPC), yet normal in its procoag ulant properties. This recently identified aPCR is in Nordic populatio ns the most prevalent and well defined genetic defect associated with disease so far described. Its prevalence in the general population ran ges from 0% to up to 15% and suggests that a positive genetic selectio n pressure has been involved. The aPCR phenotype can be assesed in vit ro by measurement of the prolongation of the activated partial thrombo plastin time in the presence of aPC, whereas the aPCR genotype is stud ied using polymerase chain reaction searching for the Arg to Gin mutat ion in the coagulation factory gene. Some acquired conditions such as the presence of lupus anticoagulants, antiphospholipid antibodies, pre gnancy, liver disease and contraceptives may lead into the aPCR phenot ype. The aPCR search must be the initial step in the study of a patien t with thrombophilia, either inherited or acquired; aPCR together with protein C, protein S and antithrombin III explain 60 to 70% of cases of familial thrombophilia.