Things that affect our INR
This was a case control study conducted at the Mass Gen in Boston. The study was conducted in patients attending the anticoagulant therapy unit (2000 patients) over a single year who had been on warfarin for at least one month, had a target INR of 2.0 to 3.0, and were able to participate in a telephone interview personally or through their carer.
Participants were identified from a daily log of INR tests. Cases were those with an INR greater than 6.0 reported within 24 hours, whose target INR was 2.0 to 3.0; results were verified with a duplicate test. Controls were randomly selected from patients whose target was 2.0 to 3.0 and who had actual values of 1.7 to 3.3.
Some selected cases and controls were ineligible because they did not speak English or because they did not have a telephone, and a few declined to participate. For the others two trained interviewers conducted a scripted interview lasting 10-15 minutes asking about the four weeks before the test. It asked about medicines, newly prescribed medicines, over the counter medicines, dietary habits, alcohol consumption, and prescribed and consumed warfarin doses. Dietary questions specifically asked about gross changes in eating habits, and specifically about 12 foods with high vitamin K content (avocado, broccoli, sprouts, cabbage, peas, lettuce, liver, spinach etc).
There were 93 patients with an INR of more than 6.0 (range 6.1 to 30). For most of them the raised INR represented a recent deterioration in control of their anticoagulation. The mean INR for the test before the four week study period was 2.5 for these same patients, mostly in the range 1.7 to 3.3. Cases and controls were similar in age (mean 70 years), sex (50% women), race (97% white), length of warfarin therapy, and reason for anticoagulation. For half it was atrial fibrillation.
Independent risk factors for an increased risk of INR above 6.0 were (Table 1):
- advanced malignancy,
- newly started medicines with the potential to interfere with warfarin metabolism
- taking more warfarin than was prescribed
- a decreased consumption of foods rich in vitamin K
- acute diarrheal illness
Table 1: Independent risk factors for INR above 6.0
|Risk factor||Odds ratio 95% CI|
|For increased chance of INR >6|
|Advanced malignancy||16.4 (2.4 to 111)|
|Newly started potentiating medicine||8.5 (2.9 to 25)|
|Warfarin dose more than prescribed||8.1 (2.2 to 30)|
|Eating less vitamin K rich food||3.6 (1.3 to 9.7)|
|Acute diarrhoeal illness||3.5 (1.4 to 8.6)|
|For decreased chance of INR >6|
|Eating vitamin K rich foods||0.7 (0.3 to 0.9)|
|Alcohol (half to two drinks a day)||0.2 (0.1 to 0.7)|
Eating more foods rich in vitamin K and a moderate alcohol intake of between one drink every other day to two drinks a day were associated with a lower chance of increased INR.
Paracetamol was also associated with increased risk of elevated INR. Taken mainly for acute pains, the more of it used in the week before the test, the greater the chance of a raised INR (Figure 1). More than nine 500 mg tablets a week gave an odds ratio of 7, and more than 18 tablets a week an odds ratio of 10.
Figure 1: Effect of paracetamol dose on risk of INR above 6.0