Potentiation of the anticoagulant effect of warfarin.

Accepted 29 March 1996 A 63-year-old woman with longstanding rheumatoid arthritis was receiving warfarin therapy for an aortic valve replacement. The dose of warfarin was monitored via a hospital anticoagulation clinic and remained stable at 4-4.5 mg per day with no significant bleeding or thrombotic episodes. In September 1993 the patient began attending a general-practice-based anticoagulation clinic. On 28 January 1994, her International Normalised Ratio (INR) was 9.6 (BSH reference range = 3-4.5). She was taking 4 mg of warfarin a day at this point. Following discussion with the local Haematology department, warfarin was stopped and arrangements made through her general practitioner to recheck the INR the next day. On this occasion her INR was 12.0. Clinically, she had developed some contact bleeding from the gums and some spontaneous bruising around the groin. In consultation with the Haematology department, the patient was advised to attend hospital for vitamin K administration but this was declined. It was therefore necessary to monitor the patient closely at home. She was seen in hospital on 1 February 1994 when her INR was 4.0. Her regular medication at this time was penicillamine 250 mg/day, naproxen 500 mg bid and ferrous sulphate 200 mg tid. She had been given Co-Dydramol (dihydrocodeine 10 mg and paracetamol 500 mg) on 24 January 1994 by her general practitioner, for general aches and pains. There was no clinical evidence of gastrointestinal bleeding. She had taken four tablets of Co-Dydramol for seven days, a total of 28 tablets, equal to 14 g of paracetamol. On 7 February 1994, her INR was 5.4 despite receiving no warfarin for the previous 10 days. The haemoglobin level was 6.9 g/dl and her platelet count 649 x 109/l, in keeping with recent blood loss. The following day her INR was 2.6 with haemoglobin 7.2 g/dl and warfarin was restarted, cautiously, at a dose of 3 mg/day. On 23 February 1994, the patient was prescribed Tylex (codeine phosphate 30 mg and paracetamol 500 mg) for joint pains. On 1 March 1994 her INR was checked at the hospital and was 8.5. She had taken three Tylex tablets a day for eight days, a total of 24 tablets, equal to a total paracetamol dose of 14 g. Warfarin was again stopped. On 7 March 1994 her INR was restarted at a dose of 3 mg/day. The blood results are summarised in figure 1. On 13 April 1994 the results were INR=2.7, haemoglobin 11.0 g/dl and platelets 444 x 1 09/l.