A 61-year-old woman undergoes routine evaluation. She reports no recent changes in her medications. She has a history of idiopathic deep venous thrombosis. Her only medication is warfarin, initiated 2 months ago.
On physical examination, vital signs are normal, and the examination is unremarkable.
She has an INR of 7.2.
In addition to withholding warfarin, which of the following is the most appropriate management?
A. Administer fresh frozen plasma
B. Administer prothrombin complex concentrate
C. Administer vitamin K
D. Remeasure INR in 2 days
MKSAP Answer and Critique
The correct answer is D. Remeasure INR in 2 days. This content is available to MKSAP 18 subscribers as Question 44 in the Hematology and Oncology section. More information about MKSAP is available online.
The patient's warfarin therapy should be withheld, and her INR should be remeasured in 2 days. Warfarin acts by inhibiting the synthesis of vitamin K–dependent clotting factors, which include factors II, VII, IX, and X. Variations in INR can occur with dietary changes. Other factors associated with prolonged elevation of INR include age 80 years or older, lower maintenance dose of warfarin, decompensated heart failure, active cancer, and use of medications known to potentiate the effect of warfarin. The 30-day risk of major bleeding is less than 1% with an INR between 5 and 9. Accordingly, warfarin should be withheld in patients with elevated INRs between 4.5 and 10 who are not bleeding and have no major risk factors for bleeding. Approximately one third of patients with an INR greater than 6 will still have an abnormal INR after withholding warfarin for two consecutive doses. Warfarin can be reinstituted when the INR returns to a therapeutic level.
The patient is asymptomatic, with no evidence of bleeding. Therefore, neither vitamin K nor fresh frozen plasma should be given. Patients who are not bleeding, are not at high risk for bleeding, and have an INR less than 10 can be managed simply by withholding warfarin. For patients with an INR greater than 10, oral vitamin K, 2.5 mg, should be given. Oral vitamin K and intravenous vitamin K appear equally effective and more effective than subcutaneous vitamin K or placebo for reversing excessive warfarin-induced anticoagulation.
The American Society of Hematology recommends against administering plasma or prothrombin complex concentrates for nonemergent reversal of vitamin K antagonists (including situations other than major bleeding, intracranial hemorrhage, or anticipated emergent surgery). However, the 30-day mortality is approximately 13% in patients with major bleeding during treatment with warfarin. In these patients with acute major bleeding as a result of warfarin therapy, in addition to vitamin K, prothrombin complex concentrates are preferred to fresh frozen plasma. Prothrombin complex concentrate is more effective than fresh frozen plasma for reducing 30-day all-cause mortality and the INR in patients with major bleeding or requiring surgical or invasive procedures.
- Patients with asymptomatic INR elevation between 4.5 and 10 are managed by simply withholding warfarin.