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Mr Nair and his colleagues1 reported a patient with protein C deficiency who had severe recurrent thromboembolic problems despite anticoagulant therapy. Three points for discussion arise. First, was the dose of warfarin sufficient, given the recurrent thromboses despite treatment? Although the APC ratio was normal, a case could be made for keeping the INR in such patients between 2.5 and 3.5, much as in patients with mechanical cardiac valve prostheses2, despite the increased risk of haemorrhage. Second, might there be a second thrombophilia to account for the severe familial thrombotic tendency? Perhaps genotyping for the prothrombin gene mutation or other less frequently recognized thrombophilias should be performed in addition to the factor V Leiden genotyping3, as well as serology testing for cardiolipin antibodies. Finally, the value for plasma homocysteine (88 μmol/L) seems high despite the ‘normal range’ of 50-200: most laboratories quote a normal range for total plasma homocysteine between 5 and 15, depending on age and gender4.
The patient was referred from the Middle East, where the target INR had been 2.0-3.0. Our own routine, in patients with prothrombotic conditions, is to maintain the INR between 2.5 and 3.5—as in patients with mechanical valve prostheses. I fully agree with Dr Hague's suggestion of genotyping for the prothrombin gene and testing for cardiolipin antibodies in patients with recurrent arterial thrombosis. In our patient, normal prothrombin levels deterred us from performing genotype analysis, but we will follow up this patient on these lines. The homocysteine values were derived from an assay in which the normal range was as stated. It does vary considerably between different diagnostic kits world-wide.