Naomi Landis, 78, wakes up from her afternoon nap with shortness of breath and palpitations. Mrs. Landis's daughter calls an ambulance to take her mother to the hospital. The emergency department physician diagnoses atrial fibrillation and admits her.

Now in your unit, she's on continuous cardiac monitoring and receiving a heparin infusion, warfarin (Coumadin), and a beta-blocker, atenolol (Tenormin). Her provider sends blood specimens to the lab for tests, including serum electrolytes, complete blood cell count, and thyroid function studies. To evaluate the effect of her anticoagulants, you're instructed to monitor her prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR). Over the next few days, the heparin infusion will be tapered and discontinued according to her PT and INR.

Your patient needs ongoing anticoagulation with warfarin to protect her from stroke and other thrombotic complications related to atrial fibrillation. Make sure you're prepared to explain why she'll need INR monitoring throughout treatment to maintain adequate anticoagulation and prevent complications.

A question of sensitivity

Effective and safe warfarin dosing is based on PT values, which reflect the function of the extrinsic coagulation pathway. However, because many different thromboplastins are commercially available and different labs use different test thromboplastin reagents (which activate clotting in blood specimens), PT values can vary widely among labs, undermining the test's accuracy. To compensate for these differences, the World Health Organization endorses the INR rather than the PT value as the standard for monitoring oral anticoagulant therapy.

The INR, a mathematical calculation that accounts for the differences in sensitivity between reagents, was developed to standardize PT values. In the INR system, each thromboplastin has an international sensitivity index (ISI) value, which shows how sensitive it is as compared with the international reference thromboplastin. An ISI of 1.0 means the thromboplastin has the same sensitivity as the reference thromboplastin. If the ISI is more than 1.0, the thromboplastin is less sensitive than the reference one. Commercial companies manufacturing thromboplastin preparations include the ISI with each reagent lot. The ISI is used in the formula to calculate the INR from a PT value.

Striving for an ideal

The INR goal for warfarin therapy depends on the reason that the patient needs anticoagulation, but the therapeutic INR range is generally 2.0 to 3.0 with a target of 2.5. (The main exception is treatment for patients with mechanical prosthetic heart valves, which requires a therapeutic range of 2.5 to 3.5.)

To ensure an accurate INR, blood specimens for PT testing must be drawn correctly, according to current recommendations of the Clinical and Laboratory Standards Institute.

Teach your patient that drugs and food can affect PT and INR results. (See Know the risks: Factors that affect INR.) Remind your patient to tell her primary care provider about any medications she's using, including herbal products, and to consume a consistent amount of vitamin K-rich foods and beverages from day to day. You'll also need to emphasize that she needs to take medication as directed and to keep her appointments for testing.

Mrs. Landis will be discharged with a prescription for a daily dose of warfarin. To assess the effectiveness of therapy, her primary care provider orders weekly PT and INR monitoring to ensure that her INR levels remain between 2.0 and 3.0. Mrs. Landis will return to the hospital in 4 weeks to undergo a transesophageal echocardiogram to check for clots in her heart and may need elective electrical cardioversion if her heart stays in atrial fibrillation. She'll continue taking warfarin for at least 4 weeks after successful cardioversion and will still need weekly PT and INR monitoring.

Let Mrs. Landis and her daughter know that her warfarin dosage is likely to change from week to week and to always write down dosage changes with the date so she'll be sure to take the correct, most current dosage. Teach her the signs and symptoms of bleeding and to report them immediately if they occur.

Tell her to avoid over-the-counter medications containing aspirin. She should carry a medical-alert card that says she's taking blood thinners. Give her information on preventing falls to cut down her risk of bleeding. Also tell her to use an electric razor and a soft toothbrush.

With appropriate treatment, testing, and teaching, Mrs. Landis can avoid the pitfalls of too much or too little anticoagulation. She can sidestep serious bleeding and thrombosis as she recovers from her cardiac arrhythmia.

Know the risks: Factors that affect INR

Factors that raise INR and raise risk of bleeding

* alcohol (with concomitant liver disease)

* amiodarone

* anabolic steroids

* cimetidine

* clofibrate

* cotrimoxazole

* erythromycin

* fluconazole

* fluoroquinolones

* isoniazid (600 mg daily)

* metronidazole

* miconazole

* omeprazole

* phenylbutazone

* piroxicam

* propafenone

* propranolol

* sulfinpyrazone (biphasic with later inhibition)

Factors that lower INR and raise risk of thrombosis

* avocado (in large amounts)

* barbiturates

* carbamazepine

* enteral feeds and foods containing

* high levels of vitamin K

* griseofulvin

* nafcillin

* rifampin

* sucralfate

Source: Hirsh J, Guyatt G, Albers GW, et al. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. Chest. 2004;126:172S-173S.

SELECTED REFERENCES