Warfarin toxicity is common and usually results from dose changes or drug interactions. There are few reported cases of intentional overdose. The management of warfarin overdose is usually complicated by the patient using warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus prophylaxis. Untreated patients have a significant bleeding risk, but treatment carries a significant risk of complete reversal of anticoagulation and consequent risk of thrombosis. The objective of this study was to describe warfarin overdoses and complications of treatment and develop a safe approach to management. Three patients are described. Two patients received a single 10-mg dose of vitamin K. Both required anticoagulation, and in one, warfarin resistance persisted for 2 weeks. In a third patient serial INR, factor levels and warfarin concentrations were measured, and incremental doses of vitamin K (up to 7.5 mg) were given based on INR. This patient did not require anticoagulation, and regular warfarin therapy was recommenced after 4 days. Patients intentionally overdosing on warfarin can be classified into three groups based on preexisting indications for warfarin: nontherapeutic, moderate risk, and major risk for thromboembolic complications. All patients should have regular INR measurements (6-hourly) to catch rapid rises. Patients not on warfarin therapeutically can be given 10 mg of vitamin K1 and repeat INRs as an outpatient. Titrating intravenous vitamin K with doses of 0.5 to 2.0 mg when INR > 5 is appropriate to reduce INR without causing warfarin resistance. The high-risk group must be kept anticoagulated, and warfarin resistance avoided.
Warfarin toxicity or overanticoagulation is a common problem and is usually the result of changes in warfarin therapy or interaction with other drugs. There have been large studies that have helped to define the risk of a raised international normalized ratio (INR) in this setting 1,2 and some controlled trials of therapy with vitamin K. 3,4 This has been discussed in more detail in a recent review. 5 Intentional overdose with warfarin is far less common, and observation and treatment of these patients are poorly defined.
Despite warfarin being an old drug that is associated with significant adverse effects in therapeutic doses, there are few reported cases of intentional warfarin overdose in the literature. 6-8 The main reason is that the patient population usually prescribed warfarin are less likely to take intentional overdoses. There are far more reports of overdose with long-acting coumarins. 9,10 Although the treatment of long-acting coumarin overdoses, such as brodifacoum, require large doses of vitamin K1 for many weeks, 10 management and observation are straightforward.
Intentional warfarin overdose is complicated by the fact that the patient is usually taking warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus prophylaxis. Treatment of these patients carries a significant risk of completely reversing the anticoagulant effect of warfarin, leading to loss of anticoagulation and consequent risk of thrombosis. Care must be taken to maintain the patient's normal anticoagulation. Often the patient requires anticoagulation with heparin in the short term, and the appropriate dose of vitamin K1 is difficult to determine, commonly resulting in a patient remaining warfarin resistant for weeks.
The objective of this study was to describe cases of intentional warfarin overdose and discuss the different options for management of these patients. In one case serial drug concentrations as well as coagulation factors were determined in an attempt to define the time course of the overdose.