High INR on warfarin

Abstract

This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.A 72 year old woman, who had been diagnosed as having recurrent deep vein thrombosis six weeks earlier, attends the practice's phlebotomy clinic for an international normalised ratio (INR) check. Her INR is greater than 8.0 (target INR range: 2.0-3.0). During the consultation, you look through her previous INR readings and notice they have been supra-therapeutic over the past two weeks despite a reduction in the dose of warfarin. What you should cover• Screen for "red flag" symptoms and signs of active, non-resolving bleeding: -Use a thorough systems review; in particular look for any evidence of gastrointestinal bleeding, such as vomiting blood and passing altered or fresh rectal blood. If ongoing gastrointestinal bleeding is suspected, inpatient warfarin reversal and an oesophagogastroduodenoscopy are indicated -Any evidence of intracranial bleeding? Ask about recent head trauma with an episode of amnesia, loss of consciousness, or more than one episode of vomiting. Examine for a reduced Glasgow coma score as well as focal neurological signs. If any of these features are present, an urgent computed tomography head scan is needed 1 -Check pulse and sitting and standing blood pressure for evidence of haemodynamic compromise.• Clarify the doses of warfarin the patient has been taking because some patients may overmedicate by mistake. If this is the case, ask how often the patient takes warfarin and at what dose. Provide appropriate written information if necessary. A dossette box might help her comply with the prescribed dose.• Is there an important medical problem, such as liver disease or cancer, that might result in impaired synthesis of clotting factors? Patients with underlying cancer are at a higher risk of haemorrhage with warfarin than with low molecular weight heparin. They are also more likely to experience polypharmacy, hepatic dysfunction, and poor nutrition, which can influence their INR control. In these patients, consider using low molecular weight heparin instead. 2• Take a thorough drug history. Ask about prescribed drugs, over the counter drugs, and herbal supplements. The cytochrome P450 enzyme metabolises warfarin, so P450 inhibitors can cause the INR to rise. Common inhibitors of warfarin metabolism include clarithromycin, erythromycin, and amiodarone-for a comprehensive list see: www.medicinescomplete.com/mc/bnf/current/bnf_ int222-warfarin.htm. Check the INR three to five days later after starting any drug that interacts with warfarin that will be taken for longer than seven days because the dose of warfarin may need adjusting. 3

Does Tooth Extraction and Perioperative Medication Affect PT-INR of Patients Taking Warfarin?

“…Our results were similar to those of other reports [12][13][14][15][16]. It is widely known that an increased age (> 75 years old), high doses of warfarin, renal failure or liver failure, diarrhea, and drug interactions can all cause increases in INR values [17]. Rice et al conducted a review of many reports and reported that many antibiotics increased INR values, although the duration of administration varied [1].…”

Incidence and predictors of excessive warfarin anticoagulation in patients with atrial fibrillation—The EWA study

“…Excessive alcohol consumption was associated with the greatest (24-fold) individual risk of EWA, reflecting the many problems of alcohol abuse with warfarin treatment: direct alcohol inhibition of warfarin breakdown, impairment of liver function and problems in drug compliance [18]. Active smokers were also found to be at risk of overanticoagulation and as with alcohol abuse, addiction treatment may prove useful also in stabilizing INR levels.…”

Does tooth extraction and perioperative medication affect PT-INR of patients taking warfarin?

“…It is widely known that an increased age (> 75 years old), high doses of warfarin, renal failure or liver failure, diarrhea, and drug interactions can all cause increases in INR values [17]. Rice et al conducted a review of many reports and reported that many antibiotics increased INR values, although the duration of administration varied [1].…”